Layered double hydroxides and human health: An overview

(2007) 103–121www.elsevier.com/locate/clay

Applied Clay Science 36

Layered double hydroxides and human health: An overview✠

C. Del Hoyo

Departamento de Química Inorgánica, Facultad de Ciencias Químicas, Universidad de Salamanca,Plaza de la Merced s/n. 37008 Salamanca, Spain

Received 17 January 2005; received in revised form 20 June 2006; accepted 21 June 2006Available online 13 October 2006

Abstract

This work summarizes the beneficial and harmful effects of layered double hydroxides upon human health. Their possible usesin pharmaceutical formulations are present in many subjects: from classical applications as orally and topical drugs to new trends ascancer therapy. The application of layered double hydroxides as excipients and their influence on the bioavailability of the organicactive principle is also reviewed. Clay-modified electrodes have received attention in the development of electrochemical sensorsand biosensors. This article also reviews this aspect for medical purposes. Finally, a summary of the fields in which layered doublehydroxides could be applied to prevent public health is also provided.© 2006 Elsevier B.V. All rights reserved.

Keywords: Layered double hydroxides; Pharmaceutical formulations; Drug; Public health

1. Introduction

Clay minerals and clays are very extended compoundson the earth surface so they constitute the main componentof soils and sedimentary rocks. Due to their presence andspecial properties that they have, mankind has used themwith therapeutic aims from prehistory, not being rare tofind references to this subject in works of classic authors.During theRenaissance andwith the appearance of the firstPharmacopeia, its use was regulated to a certain extent.

The scientific development reached during the XXthcentury has allowed to understand and to study thereasons of the useful and peculiar properties of clayminerals, directly related to their colloidal size andcrystalline structure. These properties are translated in a

✠ This work is dedicated to Dr. Ma. Angeles Vicente Hernández(deceased April 2000) in memoriam.

E-mail address: [email protected].

0169-1317/$ - see front matter © 2006 Elsevier B.V. All rights reserved.doi:10.1016/j.clay.2006.06.010

high specific surface area, optimal rheological proper-ties and/or excellent adsorptive capacity; everythingmakes cationic clays very useful for a wide range ofapplications. In the field of health, clay minerals andclays (here often named “cationic clays”) are used inPharmaceutical Technology and Dermopharmacy asideal excipients and substances of suitable biologicalactivity due to their chemical inertness and low or nulltoxicity for the patient (De Benavent, 1960; Galán et al.,1985; Cornejo, 1990; Kibbe, 2000; Carretero, 2002;López Galindo et al., 2005).

However, for reasons of utility and fulfillment ofrequisites, only a limited number of clayminerals are usedfor these aims. Among them, we should emphasizekaolinite, talc, some smectites (montmorillonite andsaponite) and fibrousminerals (sepiolite and paligorskite).The precise use of clay minerals will determine both thetechnical and legal aspects, and it is necessary to specifythe intended use of the clay mineral at issue; for instance,

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http://dx.doi.org/10.1016/j.clay.2006.06.010

Fig. 1. Schematic representation of the structure of LDs. Reprintedfrom Coordination Chemistry Reviews, 181, V. Rives and M. A.Ulibarri, Layered double hydroxides (LDH) Intercalated with MetalCoordination Compounds and Oxometalates, 61–120, Copyright(1999), with permission from Elsevier.

104 C. Del Hoyo / Applied Clay Science 36 (2007) 103–121

the treatment of a pathology (as strictly pharmacist) or thecare, correction and/or the improvement of the finaluser's appearance (cosmetic use), being the require-ments to be fulfilled are substantially different. Forinstance, a cosmetic product is any substance destinedto be put in contact with the different external parts ofthe human body (epidermis, hair, lips, teeth, etc.) just toclean, to perfume or to change the appearance or thescent, as well as to protect and to maintain them in goodconditions. However, a medicinal product is a sub-stance or combination of substances administered to thehuman being with the objective to treat or to prevent adisease, to make a diagnosis or to recover, to correct orto modify the altered physiological functions (A.A.V.V.,2001a,b, 2002, 2004, 2005a,b; Real FarmacopeaEspañola, 2005).

The selection of suitable excipients has specialimportance in the pharmaceutical formulation. Excipientsare auxiliary substances that make presentable theformulation. These substances have to facilitate the ad-ministration of the active principles, to improve theireffectiveness and to assure the stability limit in their use bythe patient (Weiner andKotkoskie, 1999). In addition, theymust be innocuous and have a pleasant flavor, scent andcolor. Certain clays fulfill the mentioned characteristics,not being toxic nor irritating at the levels required forpharmaceutical excipients, reason why they are includedin the Inactive Ingredients Guide (1996) published by theFood and Drug Administration (FDA, USA).

In addition, because of their biological activity,clays are used as active principles in formulationsrequiring adsorbent products, sterilizers, antiinflam-matory agents or detergents, being present in the com-position of almost a hundred of commercial products(Goldstein, 2001).

It is well-known, in addition, that most of clay min-erals used in Pharmacy can interact with other com-ponents of the formulation and, in the specific case ofthe drug–clay interaction, the bioavailavility of the samedrug might be affected. Several reports have evaluatedthe effect that factors such as the ionic force, thedielectric constant or polymer addition have on theliberation of the active principle, confirming the ionicinterchange being the main adsorption mechanism. Thechance of taking advantage of these interactions hasbeen raised in the last years, including biopharmaceu-tical objectives (modification of drug liberation or itssolubility), pharmacological targets (to avoid or todiminish adverse effects) and chemical factors (increaseof the stability) (Gibson, 2001).

Summarizing, clays are found in solid forms ofadministration (tablets, capsules, granulates and dusts),

liquid (suspensions and emulsions) and semisolids(ointment, pastes), for their topical application as wellas for their oral administration. In all cases, it isnecessary to make sure that the clay fulfills a series ofchemical (stability, purity and chemical inertia), phys-ical (water texture, content, particles dimensions) andtoxicological requirements (non-toxic, security andmicrobiological purity) (Lieberman, 1998).

Layered double hydroxides (LHDs), also calledanionic clays, display unique physical and chemicalproperties surprisingly close to the properties of clayminerals. The general terms hydrotalcite-type (HT)compounds is also widely used, probably due to the factthat most of its characterizations have been carried outon hydrotalcite (a Mg,Al hydroxycarbonate), and that itcan be easily and inexpensively synthesized. The nameLDH is derived from the early works of Feithnecht, whocalled these compounds “Doppelschichtstrukturen”(double sheet structures), hypothesizing a structurewith intercalated hydroxide layers. This hypothesiswas refuted many years later on the basis of singlecrystal XRD analysis, which showed that all the cationsare placed in the same layer, with the anions and watermolecules located in the interlayer region, Fig. 1.However, it must be pointed out that the terms HTcompounds or anionic clays also are not generallyaccepted, taking into account that in the first case the

105C. Del Hoyo / Applied Clay Science 36 (2007) 103–121

term refers strictly to a specific mineral and that thesecompounds do not fulfill some clay requirements, forexample, the very small particle size (Cavani et al.,1991).

Several reviews have been published about cationicand anionic clays and their thousand applications (Cavaniet al., 1991; Konta, 1995; Trifirò and Vaccari, 1996;Vaccari, 1998; Rives and Ulibarri, 1999; Vaccari, 1999;Murray, 2000; Hu et al., 2001; Rives, 2001; Sels et al.,2001; Wypych and Satyanarayana, 2004; Serwicka andBahranowski, 2004) but no so many focused on theireffects upon human health (Carretero 2002, Constantinoand Nocchetti, 2001).

Synthetic layered double hydroxides, as such or,mainly, after thermal decomposition, find many indus-trial applications and probably more will be found in thefuture in unexpected areas (Fig. 2). Furthermore,although the available literature data on layered doublehydroxides is significantly less extended than that forclay minerals, layered double hydroxides are the mostpromising precursors of multicomponent catalysts formany catalytic reactions of industrial interest (Vaccari,1999, Rives, 2001).

Up to now, cationic clays had been more widelyused and studied in the health field than layered doublehydroxides. Nevertheless, in the last decade and, dueto the increasing development of the research con-cerning layered double hydroxides, we try to gather inthis paper a compendium of the achievements thathave been made in the last years within the field ofthe health and the pharmacy with these two groups ofmaterials.

Fig. 2. Main industrial applications of LDHs(as such or after thermaldecomposition). Reprinted from Catalysis Today, 11, F. Cavani, F.Trigirò and A. Vaccari, Hydrotalcite-type anionic clays: Preparation,properties and applications, 173–301, Copyright (1991), withpermission from Elsevier.

2. Layered double hydroxides

The most interesting properties of these layereddouble hydroxides may be summarized as follows:

(A) High specific surface area (100±300 m2/g).(B) Homogeneous dispersion of the metal ions

thermally stable also at reducing conditions,with formation of very small and stable metalcrystallites (This is a contradiction! What do youmean?). Impregnation procedures for the prepa-ration of metal catalysts normally cannot achievesuch a high degree of metal dispersion.

(C) Synergetic effects between the elements, due tothe intimate dispersion which favors, for example,the development of unusual basic or hydrogenat-ing properties. It is worth noting that basic prop-erties depend significantly on the composition andthe calcination temperature.

(D) “Memory effect”, which allows reconstructionunder mild conditions (after calcination until500 °C) of the original structure by contact withsolutions containing various anions.

(E) Good anion exchange capacities.

Papers about nocive effects of these clays uponhuman health are lacking, probably because layereddouble hydroxides currently used are synthetic and onlya few of them exist in nature and, then, the exposure riskis much more smaller than for the cationic clays.

Tronto et al. (2001) intercalated a variety of anions ofpharmaceutical interest, such as salicylate, citrate,glutamate and aspartate, using two different synthesismethods, a direct one (coprecipitation) and an indirectone (anion exchange of dodecylsulfate samples).

Other molecules of biological interest have beenintercalated into layered double hydroxides, such assorbic acid (Meng et al., 2005), biocatalysts (Rahmanet al., 2004, 2005), porphyrin (Barbosa et al., 2005),nucleotides (Tamura et al., 2004; Aisawa et al., 2005),vitamins (Hwang et al., 2001) and amino acids andpeptides (Newman et al., 2002; Aisawa et al., 2004;Nakayama et al., 2004; Yuan et al., 2004a,b;Kottegoda and Jones, 2005; Seftel et al., 2005;Gerstel et al., 2006). Aisawa et al. (2003) intercalatednon-ionic pentoses (ribose and 2-deoxyribose) into theMg–Al and Zn–Al layered double hydroxides atambient temperature by the calcination–rehydrationreaction using Mg–Al and Zn–Al oxide precursorscalcined at 500 °C. Moujahid et al. (2003) carried outthe adsorption of styrene sulfonate vs. polystyrenesulfonate on layered double hydroxides.


Hibino (2004) (LDHs) studied the intercalation ofseveral amino acids into Mg–Al LDH. The interlayerenvironment was attractive to formamide, because ofhydrogen bonding, so that penetration of formamidecould cause delamination. Some of the amino acidintercalates were successfully delaminated in formam-ide, but others were not. The compounds that could notbe delaminated had a high amino acid content, ex-ceeding 15–20% of charge occupation. At that density,close-packed amino acids were likely to be linked toanother and to the host layers via hydrogen bonds, andtherefore formamide presumably could not open theinterlayer spaces and penetrate between the layers to alarge extent. However, there was not a clear lowerthreshold for charge occupation of the amino acids; evenLDHs with charge occupations of less than 1% under-went delamination.

Tamura et al. (2004) studied the intercalation ofadenosine triphosphate (ATP) into Mg–Al LDH as amodel for a drug delivery system. Two intercalationmethods were used: ion exchange using nitrate as theinterlayer anion and coprecipitation, adding Mg2+ andAl3+ ions into a sodium hydroxide solution.

As layered double hydroxides are biocompatiblesystems (Cavani et al., 1991), they can be used inpharmaceutical technologies (Costantino and Nocchetti,2001; Khan et al., 2001) and in medicine as drugsupports or matrices. Once encapsulated, the drug couldbe released at a rate determined by pH. Mg–Al LDHhave already found pharmaceutical applications asexcipients (Tomohisa and Mitsuo, 1998; Woo and Yi,2000), drug stabilizers (Ueno and Kubota, 1987; Doiet al., 1989), ingredients in sustained-release pharma-ceuticals containing nifedipine (Doi et al., 1985),components in adhesives for transdermal delivery,(Koide and Ozeki, 1987), for symptomatic treatmentof peptic ulcers (Goodman-Gilman et al., 1975), for thetherapy of digestive disorders (Hashimoto et al., 1997)and for preparation of aluminium magnesium salts ofantipyretic, analgesic and antiinflammatory drugs(Kyowa Hakko Kogyo Co., 1985). Its use in cosmeticshas also been described (Nakane et al.,1991; Koideet al., 2000).

The possibility of layered double hydroxides as“molecular containers” for pharmaceutical agents hasalso to be considered. Wei et al. (2005b) preparedintercalated L-Tyrosine-LDHs systems by coprecipita-tion. L-Tyrosine (4-hydroxyphenylalanine, representedas L-Tyr) is a non-essential amino acid that is syn-thesized in the body from phenylalanine. Deficiencies inL-Tyr have been related to depression and L-Tyrsupplements in the diet have beneficial effects. L-Tyr

is also used in the treatment of vitiligo, dementia and ineasing the adverse effects of stress. It was found thatintercalation into LDHs can inhibit racemization ofL-tyrosine, keeping its stability, under the influence ofsunlight, high temperature or ultraviolet light. Therefore,these LDH materials may have potential use as “mole-cular containers” for storing or transporting unstablechiral biomolecules or pharmaceutical agents.

Concerning the interaction between antibiotics andLDH, there are some emphasized works. Mohanambeand Vasudevan (2005b) have intercalated carboxy-methyl beta-cyclodextrin cavities within the galleriesof Mg–Al layered double hydroxide. The cyclodextrinfunctionalized LDH adsorbed neutral and nonpolarguest molecules. Wei et al. (2005a) studied the thermaldecomposition of an intercalate derived from Mg–AlLDH and hexa-sulfated beta-cyclodextrin [NaSO3-β-CD]. Li et al. (2006) reported that phenoxymethylpe-nicillin has been reversibly intercalated into a layereddouble hydroxide, and the resulting system exhibitedeffective anti-bacterial activity. Huang et al. (2005)prepared samples of layered double hydroxides by amethod involving separate nucleation and ageing steps,using varying [Mg2+]/[Al3+] ratios and different ageingconditions. Bactericidal experiments against Bacillussubtilis var. niger and Staphylococcus aureus werecarried out using materials formed by calcination of theLDHs at 500 °C. MgO is very readily hydrated and thatreaction with dissolved oxygen affords superoxideanions O2

(−), which attack the secondary amide groupof proteins leading to destruction of the bacteria. Thebactericidal activity of the MgO increased with specificsurface area because this leads to an increased numberof surface hydroxyl groups and higher concentrations ofO2(−) in solution. The bactericidal ability of MgO

therefore increased with decreasing particle size.Bioadhesion is defined as the adhesion of polymers

and biological structures and is used for many hard- andsoft-tissue applications. This term is applied when thesubstrate is mucus. Some researchers have concludedthat polymer characteristics are necessary for bioadhe-sion: high-molecular weight, strong hydrogen bondinggroups (OOH and OCOOH), anionic charge (COO- andSO3

2-), sufficient chain flexibility and surface energyproperties favor the spread onto mucus. Drug-deliverysystems with bioadhesive drug carriers have becomeincreasingly important because of their ability to adhereto mucosal surfaces of the buccal and skin and therebyincrease therapeutic efficiency. Typical polymers usedas bioadhesive drug carriers include carboxymethylcel-lulose, poly(acrylic acid) (PAA), poly(methacrylic acid)and hydroxypropyl methylcellulose. Lee and Chen


(2004) prepared a series of nanocomposite hydrogelsused for bioadhesive from acrylic acid, poly(ethyleneglycol) methyl ether acrylate, and intercalated hydro-talcite by photopolymerization. Lee and Chen (2005)studied the effect of intercalated hydrotalcite onswelling and mechanical behavior for poly(acrylicacid-co-N-isopropylacrylamide)/hydrotalcite nanocom-posite hydrogels. Hydrotalcite acted as an intercalatingagent.

3. Beneficial effects upon antiinflammatory therapy

Hydrotalcite-like layered double hydroxides can beused to intercalate drugs and de-intercalate them in orderto prepare a controlled release formulation. Ibuprofen,α-methyl-4-(2-methylpropyl)benzene acetic acid anddiclofenac, [2-(2,6-dichloro-phenylamino)-phenyl]acetic acid are non-steroidal antiinflammatory drugsused for the relief of symptoms of osteoarthritis andrheumatoid arthritis. They are used both in the treatmentof acute flares and in the long term management of thesediseases. Their use is often limited by the frequent sideeffects affecting both the central nervous system and thegastrointestinal tract. These side effects are also aconsequence of high plasma levels following the admin-istration of conventional formulations. These problemscould be reduced by a formulation showing controlleddrug release. Ambrogi et al. (2001) observed that ibu-profen anions exchanged all chloride ions of hydro-talcite-like compounds, producing an intercalationcompound with a drug loading of 50% w/w. Dissolutiontests showed that the drug release was changed com-pared to the commercial formulation Neo-Mindol® andthe physical mixture of ibuprofen and the chloride formof the LDH. Diclofenac was also intercalated by severalmethods, making possible the use of LDHs as matricesfor non-steroidal antiinflammatory (Ambrogi et al.,2002; Dupin et al., 2004).

Gordijo et al. (2005) reported the immobilization ofibuprofen and copper-ibuprofen drugs on layered doublehydroxides. Ibuprofen was intercalated in LDHs by: ionexchange, reconstruction and coprecipitation. The drugand the copper-ibuprofen were also immobilized byadsorption on the external LDH surfaces. Pharmacolog-ical interests were compared considering the amounts ofimmobilized drugs and, most of all, their bufferingproperties. Samples obtained by exchange and copreci-pitation exhibited poor buffering property, but containedhigh amounts of drug. Adsorption samples despite theirbuffering property contained low amounts of ibuprofen.The reconstructed hybrid systems combined significantamounts of immobilized drug with good buffering

property. These organic–inorganic materials based onLDHs may be an interesting new formulation aiming todecrease gastric irritation mainly due to their bufferingproperty.

Solubility is an important physicochemical propertyfor a drug because it plays a key role in drug liberation,absorption and, as a final result, in its bioavailability. Animprovement of the solubility of poorly soluble drugs isan important purpose for the development of a suitableformulation for oral administration.

Ambrogi et al. (2003) described a new approach ofimproving drug solubility by using LDHs as carrier. Atacidic pH values (pHb4) Mg–Al hydrotalcite dissolvesand released immediately the drug in molecular formsuitable for absorption. Indomethacin, 1-(4-chloroben-zoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid, tia-profenic acid, 2-(5-benzoyl-2-thienyl)propionic acid,and ketoprofen, 3-benzoyl-amethylbenzeneacetic acidwere chosen as models of poorly soluble drugs.

Hydrotalcite has barrier properties similar to those ofgastric mucous, and may represent (?)mucosal protec-tion by its ability to maintain or mimic the barrierproperties of gastric mucous gel. Therefore, besides theincrease of solubility, this intercalation product couldalso lower the direct gastrolesivity of antiinflammatorydrugs. Furthermore, as the drug is released in molecularform, high local concentration of the drug is avoided.Del Arco et al. (2004a) carried out a pharmacologicalstudy in vivo of the interaction between hydrotalcite andindomethacin showing that intercalation of the drugreduces the ulcerating damage of the drug.

The intercalation compounds obtained with all anti-inflammatory drugs are hybrid systems, which, at roomtemperature, simultaneously exhibit fluid and solid stateproperties. In acid pH hydrotalcite quickly dissolvesreleasing the drug in molecular form. Sun et al. (2005)and Zhang et al. (2005) carried out the synthesis andcharacterization of nanoscale magnetic drug-inorganiccomposites by direct coprecipitation. Intercalation ofcaptopril (Cpl) and 5-aminosalicylic acid (5-ASA) nZn–Al LDH coated on MgFe2O4 magnetic coreparticles was reported. TEM and XPS analysis revealedthat a core–shell structure composed of a drug-LDHslayer and a MgFe2O4 particle core due to Zn–O–Mgand/or Al–O–Mg bonds. VSM measurements showedthat the novel magnetic drug-inorganic compositespossess considerable magnetization.

Another important pharmaceutical use of hydrotal-cite-like compounds could be drug stabilizing duringstorage. The active ingredient was protected by thelaminar structure and, in the case of the used drugs,photodecarboxylation was prevented because of the


interaction of the carboxylate groups and the positivelayer charges. During storage the layers of hydrotalcite-like compound supply a well-defined and relativelyhydrophobic microenvironment for these anti-inflam-matory guest molecules, useful to control guest hydro-lysis and photoreactivity.

Fenbufen or γ-oxo-[1,1'-biphenyl]-4-butanoic acid],C6H5C6H4C(O)CH2CH2COOH, is a non-steroidal anti-inflammatory drug also used for the relief of symptomsof rheumatoid arthritis and osteoarthritis. It is also usedin the treatment of both rachitis and gout. Its use is oftenlimited, by the frequent side effects that affect both thegastrointestinal tract and the central nervous system.These side effects also result in a decreased leucocytecount and an increase in aminotransferase. Controlledrelease of the drug can be expected to significantlysoften these harmful systemic effects.

Li et al. (2004a) used Mg/Al, Zn/Al, Fe/Al and Li/Al-layered double hydroxides as host materials for drug-LDH host–guest supramolecular structures. The anti-inflammatory drug fenbufen has been intercalated intothose layered double hydroxides by co-precipitationunder a nitrogen atmosphere. The interlayer distance inthe intercalated materials increases with increasing pHvalue, resulting from a change in the arrangement ofinterlayer anions from a monolayer into interdigitatedbilayers. Drug release investigated by a dissolution testin a simulated intestinal fluid (buffer at pH 7.8) showedthat the drug release was slow, especially in the case ofMg/Al LDHs, suggesting that these drug-inorganichybrid materials can be used as effective drug deliverysystems.

Because of the basicity of LDHs, however, their useas drug delivery systems will be questionable in thestomach where pH is 1.2. A core–shell material hasbeen prepared (Li et al., 2004b). Fenbufen-intercalatedLDHs as the core was coated with enteric polymers,Eudragit® S 100 or Eudragit® L 100 as a shell, giving acomposite material which showed controlled release ofthe drug under in vitro conditions which modelled thepassage of a material through the gastrointestinal tract.

Naproxen, (+)-6-methoxy-a-methyl-2-naphthaleneacetic acid, is another non-steroidal antiinflammatorydrug frequently used in the treatment of rheumaticdiseases and is poorly water soluble. It is not easilytransformable into the amorphous state by freeze dryingor spray drying. To be most effective for drug therapy,the desired pharmacological response must be obtainedat the target without harmful interactions at other sites.Several studies (O'Hare, 2002; Del Arco et al., 2004b;Wei et al., 2004) have intercalated naproxen into layereddouble hydroxides. The thermal stability of the inter-

calated naproxen was significantly enhanced comparedwith the pure form before intercalation. This hybridmaterial may have prospective application as the basisof a novel drug delivery system.

Mohanambe and Vasudevan (2005a) made a compar-ison of molecular dynamics simulation and measure-ments using three antiinflammatory drugs: Ibuprofen,indomethacin and diclofenac intercalated into a Mg–AlLDH. All these drug molecules are arranged as bilayersin the interlaminar space. Whereas the structure of theintercalated ibuprofen was identical to that of the mole-cules outside the layers, spectroscopy as well as mole-cular dynamics simulation showed that the geometry ofdiclofenac and indomethacin changed after confinementwithin the galleries of the LDH. The change in geometryof diclofenac and indomethacin by intercalation wasshown to originate from the electrostatic interaction be-tween the electronegative chlorine atoms on the drugmolecule and the positive layer charges. These changes inthe geometry of the intercalated drug molecules explainthe observed interlayer spacing without interdigitatedbilayers, which would otherwise have been necessary ifthe structure of the drug molecules had remained iden-tical to that outside the layers. Comparisons of experi-mental measurements with simulation have provided amore detailed understanding of the geometry and organi-zation of flexible drug molecules confined in the inter-layer spaces of LDHs.

4. Beneficial effects upon skin

It is well established that UV radiation represents themost important physical attack to which the skin isexposed. Biologically active solar radiation is mainlyrepresented by UV-B and to lesser extent by UV-A. UV-Cradiation from sunlight reaches the surface of the earthbecause of the destruction of the ozone layer, beingresponsible for skin cancer. UV-B radiation penetratesdeeply into the skin to the basal layer while UV-Aradiation reaches the chorion derma causing modifi-cation of skin layers that may be responsible for skinageing increase. In particular, reactive oxygen speciescause most of the deleterious effects of UV light onskin because they provoke a severe decrease of itsnatural antioxidant composition. An overproduction ofnitric oxide by the keratinocytes leads to erythema andinflammation processes.

Many molecules can be used to protect the skin fromthe sun damage and among these, ferulic acid, 4-hydroxy-3-methoxycinnamic acid, was found to be promising asactive substance for sunscreen formulation. Its antioxi-dant properties derive from its free radical scavenging


ability; ferulic acid acts as a scavenger against hydroxyland peroxyl radicals and superoxide anions, inhibitingpropagation of lipid peroxydation chain reaction. It alsoreduces the UV-B-induced erythema because of its higheffectiveness in scavenging nitric oxide, and provides ahigh degree of skin protection acting as UV absorberscreen.

Rossi et al. (2005) have intercalated ferulic acid intoa hydrotalcite-like LDH by a simple ion exchange pro-cess. The LDHn protected ferulic acid from degradationdue to irradiation and improved potentially ferulic acidsunscreen properties in the region around 300 nm. TheLDH protected ferulic acid even when formulated into asilicone cream by preventing its release from the matrix.Hence, it was demonstrated that the intercalated com-pound could be formulated into a potentially usefulsilicone-based cream for sunscreen formulation.

The p-aminobenzoic acid (PABA) is a UV-B absorber(200–313 nm) used as a sunscreen component as early asthe 1920s and lasted since when dermatologists becameaware that it was a fearful photosensitizer. In fact it tendsto cross-sensitize with other para-molecules and is re-sponsible for harmful cutaneous reactions like irritation,contact orticaria and allergic and photoallergic dermatitis.PABA can decompose to a nitrosamine degradationproduct with a known potential carcinogenic effect sothat, since the late 1980s, it has been practically with-drawn from the sunscreen and cosmetic market, and mostproducts proclaim that they are ‘PABA-free’. At present,photodegradation of chemical sunscreens has beenreduced by providing a protective film around the re-acting molecule, by incapsulation in liposomes, micro-spheres and in glass beads, by complexation withcyclodextrines or by incorporation in nanoparticles.

The expected advantages of sunscreen intercalationin layered double hydroxides are: (1) sunscreenstabilization because the interlayer region of a lamellarhost can be considered a microvessel in which ananionic molecule may be stored; (2) absorption of ultra-violet lights in both the UV-A region and the UV-Bregion, even in the UV-C region sometimes and (3)absence of a close contact between skin and filter withthe consequent elimination of allergy problems. Perioliet al. (2005) have designed a new protection model; theyreport the studies on the intercalation products of PABAinto Mg–Al and Zn–Al layered double hydroxideslamellar structures and the properties of the relativecosmetic formulations.

Feng et al. (2006) observed the interaction betweenthe organic anion of 2-hydroxy-4-methoxybenzophe-none-5-sulfonic acid (HMBA), a highly efficient UVabsorber, and Zn–Al-LDHs. The synthesis process

consists in a reaction in air of HMBA with an LDH-carbonate precursor obtained by a process involvingseparate nucleation and aging steps. The obtainedHMBA–LDH intercalation system exhibits an enhancedphoto- and thermal stability without affecting its UVabsorption capacity; this shows that the hybrid materialhas potential interest as a UV absorber.

5. Beneficial effects upon cancer therapy

Gene therapy is gaining attention for treatment ofgenetic deficiencies and life-threatening diseases. For theefficient introduction of foreign DNA into cells, a carriersystem is required. Both viral and nonviral vectors arepresently under research. Generally, nonviral vectors,consisting of a targeting ligand and a DNA-bindingmoiety, have great potential for gene therapy due to theirsafety, simplicity, and capacity for packaging very largeDNA molecules. The major limiting factor in the dev-elopment and application of these vectors has been poortransfection efficiency due, primarily, to endosomaldegradation.

Nonviral vectors that exploit receptor-mediated endo-cytosis to target and enter the cells have great potential foruse in gene therapy. In general, these vectors consist ofplasmid DNA complexed with a polycationic element,often poly-L-lysine, which is conjugated to a targetingligand molecule. These vectors have several advantagesover viral vectors for gene therapy. Apart from theirsimplicity and lack of pathogenicity, they can target andtransfect cells displaying a specific receptor. Furthermore,much larger nucleic acid molecules can be packaged bythese vectors than by viral vectors. However, their maindisadvantage is that their transfection efficiency isgenerally much lower than the transduction efficiencyof viral vectors. Endosomal degradation is a major causeof poor transfection efficiency, which has been demon-strated in many nonviral receptor-mediated vectorsincorporating endosomolytic agents such as inactivatedadenoviral capsids or amphipathic peptides. The trans-fection efficiency of an antibody–polylysine conjugatewas enhanced more than 10-fold by incorporating acationic liposome in the complex. Enhanced expressionwas attributed to lipid-mediated destabilization of theendosomal membrane. However, the materials are knownto present (i) sensitivity to serum, antibiotics, and tocertain cell culture media; (ii) cytotoxicity; and (iii)serious limitation by the overall level of transfectionand time dependency of the experiments. Thus, thereremains a need for less toxic and more efficient de-livery vehicles for oligonucleotides and other genebased therapeutics.


To overcome the drawbacks of nonviral vectordescribed above, Kwak et al. (2002) designed and syn-thesized c-myc antisense oligonucleotide (As-myc)–LDHhybrid by simple ion exchange. As-myc has been chosenbecause the As-myc–LDH hybrid can easily be prepared,and As-myc itself has a detectable function in cells. Inaddition, it represents a useful model system for studyingthe role of proto-oncogenes in cellular proliferation anddifferentiation because the human promyelocytic leuke-mia cell line, HL-60, over expresses the c-myc proto-oncogene. The negatively charged As-myc molecule caneasily be intercalated into LDH by ion exchange.Therefore, the As-myc–LDH hybrid becomes thermody-namically stable due to enhanced electrostatic interaction.This is the reason why the LDH hybrid can protect theAs-myc from degradation. Moreover, the charge neutral-ization enhances the transfer of As-myc into HL-60 cellsthrough endocytosis. In the cells, however, interlayeroligonucleotide would partially be replaced by otheranions in the cytosol, in such a way that the encapsulatedoligonucleotide could be released inside the cell.

In this way, that antisense oligonucleotide moleculespackaged in the LDHs can enter cells, presumablythrough endocytosis or phagocytosis. The leukemia cellswere used to explore the LDH's potential as gene carriers.Treatment of leukemia cells with LDH-encased As-mycoligonucleotides that disrupt a gene in the cells inhibitstheir growth by 65% when the HL-60 cells are incubatedwith 20 AM As-myc–LDH hybrid. Unpackaged, thesame oligonucleotides cannot enter the cells and have nosignificant effect. However, LDH itself is found to benoncytotoxic on HL-60 cells (leukemia cells).

Recent research showed nanobiohybrids as a novelgene and drug delivery systems. Leroux et al. (2005)reported the formation of Mg–Ga LDH–DNA nanohy-brids using the coprecipitation method. This “self as-sembly” approach enabled the incorporation of longDNA fragments. X-ray diffraction analyses indicated aparallel orientation of the DNA double helices in theinterlamellar space with respect to the hydroxide sheets.The presence of adsorbed DNA macromolecules alsoinhibited the crystal growth: hydrodynamic diametermeasurements revealed homogeneous populations ofparticles with a mean diameter ranging from 90 to150 nm, compatible with cell penetration through endo-cytosis. Concerning the surface charges of this new DNAdelivery system, zeta-potential measurements indicatednegative values between −20 and 40 mV which suggestincomplete DNA intercalation. Nevertheless, this lownegative surface charge might be suitable for protectingDNA from extra-cellular degradations without prevent-ing cell penetration.

Tyner and Giannelis (2004) and Tyner et al. (2004)developed a novel method to deliver poorly water solubledrugs by intercalation into a LDH host. Camptothecin isan alkaloid derived from the Chinese tree camptothecaacuminata. Camptothecin and its derivatives are unique intheir ability to inhibit DNA topoisomerase, trapping thisenzyme, inhibitingDNA replication and killing the cancercells. This drug is first loaded into anionic micelles usingan oil in water emulsion system. The drug-loaded micelleis then ion exchanged into a Mg–Al LDH to form acamptothecin–LDHnanobiohybrid. The drug is protectedin spite of the organic environment of the micelle and therobustness from the inorganic layers. 9 LGlioma cells thathad camptothecin nanobiohybrids delivered to themshowed comparable efficacy to the pure drug with thecontrols of the pristine layered double hydroxides andsurfactant showing no inhibition of growth. The efficacycombined with controlled release properties and target-direction of the hybrids indicates a D-eat potential for thisdelivery system.

Kwak et al. (2004) considered that the particle size ofLDHs could be controlled in such a way that theparticles would be suitable for intravenous injection. Itis generally known that the average diameter ofcapillaries is around 10 μm and a normal red bloodcell is 6–8 μm in diameter. The most common size ofsmall lymphocytes ranges in size from 6 to 10 μm. Incomparison, it can be expected that the particle size ofLDHs is not so large as to block a capillary.

Wang et al. (2005) intercalated fluorouracil intolayered double hydroxides by reconstruction. Fluoroura-cil belongs to the group of medicines known as antime-tabolites. It is used to treat almost all kinds of digestivesystem cancer. Fluorouracil interferes with the growth ofcancer cells, which are eventually destroyed. Powder X-ray diffraction and spectroscopic analysis indicate that thedrug molecule is stabilized in the host interlayer byelectrostatic interaction and intermolecular interaction,and that the fluorouracil orientation is different whenchanging the method of ageing or the swelling agent. Therelease studies showed that a rapid release of the drugduring a short time period of 40 min was followed by amore sustained one, and that the total amount of drugreleased from the hybrid material into the aqueous solu-tion was almost 87% and 74% at pH 4 and 7, respectively.The studies mentioned above suggest that LDHs mightprovide a basis of useful drug delivery systems.

6. Biosensors based on clay-modified electrodes

A chemical sensor is a small device that, as the resultof a chemical interaction or process between analyte and


the sensor device, transforms chemical or biochemicalinformation of a quantitative or qualitative type into ananalytically useful signal (Stetter et al., 2003). Allchemical sensors contain two basic components: achemical recognition system (receptor) and a transducer.Biosensors are chemical sensors in which the recogni-tion system uses a biological mechanism instead of achemical process. They can be used for medical, phar-maceutical and analytical purposes. A transducer trans-forms the response measured at the receptor into adetectable signal. Among all the chemical sensors re-ported in the literature, electrochemical sensors are themost attractive because of their remarkable sensitivity,experimental simplicity, and low cost. The signal fromthe transducer can be a current (amperometry), a voltage(potentiometry), or impedance/conductance changes(conductimetry).

Chemically reactive layers can be used for importing ahigh degree of selectivity to electrochemical transducers.Chemically modified electrodes (CMEs) provide oneapproach to the development of these analytical devices.CMEs are important constituents of both immobilizedreagent systems and sensitive layers. In trace analysis,during the accumulation reaction, CMEs preconcentratethe analyte into a small volume on the electrode, allowinglower concentrations to be measured than possible in theabsence of a preconcentrated step (adsorptive strippingvoltammetry). CME can also be applied to electroanal-ysis because of their own electrocatalytic properties and/or their capacities to immobilize electrocatalytic orbiocatalytic (enzyme) reagents that improve the sensitiv-ity and selectivity of the detection step. Most modifiedelectrodes can be obtained by covalent bonding, chemi-sorption and film deposition. Among the wide range ofelectrode modifiers, inorganic materials, such as zeolites,silica-based hybrid materials, and clays, have attractedthe attention of electrochemists, in particular for theiranalytical applications (Walcarius et al., 2001; Navráti-lová and Kula, 2003; Mousty, 2004).

Most clay minerals used at clay-modified electrodes(CLME) are smectites. They can serve as matrices forelectroactive ions because they are usually able to in-corporate ions by ion exchange, like polymeric ion-omers. Adsorption of proteins on clay mineral surfacesplays an important role, not only in fields related toagricultural and environmental sciences but also in thedevelopment of biosensors (Gianfreda et al., 2002).

Biosensors based on clay-modified electrodes havebeen developed to detect glucose (Poyard et al., 1999),cholesterol (Besombes et al., 1997), hemoglobin (Leiet al., 2002), codeine (Shih et al., 2002) and urease(De Melo et al., 2002).

Clay minerals offer attractive properties in designingelectrode surfaces for analytical applications due to theirlow cost and stability. Adsorption properties and ionexchange and have been extensively applied not only topotentiometric and amperometric determinations ofdrugs but also to biosensor development. Clay-modifiedcarbon paste electrodes have generally been used foradsorptive stripping sensors. A new alternative is clay-modified screen-printed electrodes (SPE). SPE technol-ogy offers the advantages of being simple, inexpensiveand rapid, and allows mass production of reproducibleelectrodes. Another promising method to prepare elec-trochemical sensors consists of the preparation of singlelayer clay films by the Langmuir–Blodgett method(Mousty, 2004).

Synthetic LDHs and clay mineral nanocompositesare materials of increasing interest because of theirstructural or functional behavior. For instance, organic–inorganic hybrid materials, like polymer–clay nano-composites, display properties inherent to both types ofcomponents. LDHs also constitute promising materialsfor a large number of electroanalytical applications dueto their wide range of compositions, their versability andpreparation variables that can readily modulate theiradsorption behavior, and electrocatalysis properties inregards to analytes and/or enzymes. Exciting futureprospects include the use of these synthetic materials tosingle-use sensors and biosensors.

Fernandez and Carrero (2005) reported on theelectrochemical behavior of chemically modified glassycarbon electrodes by using surfactant/clay films, [cetyltrimethylammonium bromide/LDH], containing ferro-cenecarboxylic or ferrocenedicarboxylic acid. Low con-centrations of ascorbic acid and uric acid in aqueoussolution were easily oxidized on the ferrocenedicar-boxilic acid–surfactant–clay–glassy carbon modifiedelectrode.

Shan et al. (2004) developed a novel inexpensive andsimple amperometric biosensor, based on the immobi-lization of horseradish-peroxidase into redox active Zn–Cr LDH which was applied for determination ofcyanide. Darder et al. (2005) designed a new familyof functional hybrid nanocomposites based on theintercalation of naturally occurring anionic biopoly-mers including pectin, xanthan gum, alginic acid,pectin, k-carrageenan and l-carrageenan in Zn–AlLDH. The precipitation method has been successfullyemployed for the intercalation of such polysaccharideswithin the layered double hydroxides. Most of thestudied biopolymers interacted strongly with calciumions producing homogeneous gels. The preparedbiopolymer–Zn–Al nanocomposites were applied as

Table 1Patents based on layered double hydroxides (Derwent Innovations Index, 1996-2006).

Patent number/year Inventor Title Novelty

US2005238569-A1/2005 Choudary B M,Vallabha S J,Reddy B R,Mannepalli L K,Rao M M, Rao K K,Kondapuram V R

Preparation of homogeneousnanobinary/ternary metal oxy/hydroxide of layered doublehydroxides, useful as e.g.catalysts, comprises hydrolysisof metal alkoxides/metalacetylacetonates, aging,hydrothermal treatment andsupercritical drying

Preparation of (A) homogeneous nanobinary/ternary metal oxy/hydroxide of layered doublehydroxides by an aerogel protocol, comprises:hydrolysis of metal alkoxides or metalacetylacetonates in solvent mixture (alcoholsor hydrocarbons), by controlled additionof deionized water or its mixture with alcohols;aging for 6 to 16 hours; followed by hydrothermaltreatment; and finally supercritical drying toobtain a free flow powder of (A).

Use: (A) is useful as catalysts and adsorbents.The self-assembled LDH (made of (A)) is useful:as catalysts; biomaterials for gene reservoirs andcontrolled drug release, solar energy harvesters; andfor the preparation of thin films and membranes.

EP1524098-A1;US2005082710-A1;JP2005119302-A/2005

Oriakhi C,Lambright T M,Kasperchik V P,Collins D C,Farr I

Solid free-form fabrication of three-dimensional object comprisesdepositing particulate blendcross-linkable polyacid particulatesincluding polyvinyl pyrrolidone-co-polyacrylic acid, andnanocomposites in defined region

Solid free-form fabrication (SFF) of three-dimensional object comprises depositingparticulate blend in defined region, the particulateblend including reactive glass ionomer particulates,cross-linkable polyacid particulates includingpolyvinyl pyrrolidone-co-polyacrylic acid, andnanocomposites; ink-jetting aqueous binder ontopredetermined area of particulate blend to formhydrated cement in predetermined area; andhardening hydrated cement.

US6814871-B1/2004 Bem D S,Willis R R,Ellig D L

Removing pollutants e.g. ammoniumand phosphate ion from an aqueousstream, e.g. water, involves contactingthe aqueous stream with a shaped ionexchange composite at ion exchangeconditions

Removing pollutants from an aqueous streaminvolves contacting the aqueous stream with ashaped ion exchange composite at ion exchangeconditions to remove at least some of thepollutants.

WO2004092064-A1;EP1631524-A1;AU2004229586-A1/2004

Gillman G P,McCallum D A

Manufacture of ammonium nitrateand layered double hydroxidescontaining nitrate comprises mixingnitrate containing first metal withnitrate containing second metal orcompound containing second metaland ammonium hydroxide

Manufacture of ammonium nitrate and layereddouble hydroxides containing nitrate as aninterlayer anion, comprises mixing a nitratecontaining a first metal with a nitrate containinga second metal or a compound containing asecond metal and ammonium hydroxide to formthe layered double hydroxides containing nitrateas an interlayer anion and ammonium nitrate.

Use: The method is used in the manufacture ofammonium nitrate and LDH containing nitrate.The ammonium nitrate can be used in themanufacture of explosives and fertilizers. TheLDH containing nitrate may be used as a fertilizer.

WO2004000757-A1;CN1467177-A;CN1189427-C/2004

Duan X,Ren L,Li D

Packaging of anionic supermolecularinteraction-structured materialscomprises selecting special guestmolecules as well as controllingdensity of ions and laminar cation,applicable in functional materials

Packaging anionic supermolecular intercalation-structured material comprises the synthesis ofhydrotalcite carbonate-LDHs (layered doublehydroxides); adding excess guest molecule togive a clear solution; reacting with 0.01–0.5 Msodium hydroxide, filtering, washing and dryingto afford the intercalation-packaged guest-supported LDHs laminar column material.


Table 1 (continued)


US6579460-B1/2004 Willis R R,Bem D S,Ellig D L

Removal of toxins e.g. ammoniumion from fluid consisting of blood ordialysate solution, by contacting thefluid with shaped ion exchangecomposite comprises mixture ofmicroporous cation and anionexchange compositions

Removing toxins from fluid consisting of bloodor dialysate solution, comprising contacting thefluid with a shaped ion exchange composite ation exchange conditions to provide a purified fluid,is new. The composite comprises a mixture of amicroporous cation and anion exchange compo-sitions. The cation exchange composition includeszirconium metallate and/or titanium metallate.

WO2003100052-A;WO2003100052-A1;CN1459502-A/2004

Duan X,Ren L,He J

Preparation of anionic laminarmaterial-immobilized enzymes withrecyclability for use in catalysis ofvarious reactions, based on inter-laminarly trapped guest moleculesfor crosslinking and fixation

A method for preparing an anionic laminarmaterial-immobilized enzyme comprising: (a)producing layered double hydroxides (LDHs)with laminar di- or trivalent metal cations withguest molecules in laminae; and (b) stirring theproduct with crosslinking agent as well asenzyme to form the immobilized enzyme, is new.

ZA200004598-A/2003 Kulkarni S M,Pramanik A

Production of bioabsorbable form ofiodine intercalated in interlayer spacesof layered double hydroxides involvestreating with mineral acid and/orcalcining layered double hydroxidesat predetermined temperature

An iodine intercalated in the interlayer spaces oflayered double hydroxides is produced bytreating with mineral acid and/or calcininglayered double hydroxides at 300–700 °C.

Use: For producing bioabsorbable form of iodine.

US2002095055-A1;US6455735-B1/2002

Choudary B M,Bharathi B,Kantam M L,Reddy C R V,Raghavan K V

Preparation of amine oxide used inshampoos, involves reactingtertiary/secondary amine withhydrogen peroxide, in presence ofheterogeneous layered doublehydroxide exchanged with anionsof transition metal oxide

Providing an eco-friendly and simple process forN-oxidation of secondary and tertiary aminesusing layered double hydroxides exchanged withanions of transition metal oxides as a catalyst,which is cheaper, non-corrosive and recyclable.

Use: For preparing amine oxides used in thepreparation of hair conditioners and shampoos,toothpaste, laundry detergent powder and fabricsofteners, toilet soap bars and cosmetics,surfactants and in other applications as syntheticintermediates and excellent spin trapping reagents.

EP1209142-A;US6387033-B1;JP2002167221-A;EP1209142-A1;EP1209142-B1;DE60011101-E/2002

Choudary B M,Chowdari N,Kantam M L,Raghavan K V,Reddy C V,Chowdari N S,Reddy C R V

New layered double hydroxidesexchanged with osmate useful ascatalysts for preparing e.g. vicinaldiol compounds

Layered double hydroxides exchanged withosmate (LDH-osmates) (I) are new.

Use: Used as catalysts for preparing vicinaldiol compounds (preferably chiral vicinal diolcompounds) useful as intermediates forpharmaceuticals such as taxol side chains ananticancer drug, diltiazem, calcium antagonistsand chloramphenicol antibiotic.

WO200155057-A;WO200155057-A1;AU200126540-A;EP1254089-A1;KR2002074217-A;CN1404460-A;JP2003520752-W;US2003150249-A1;ZA200205519-A;NZ520423-A;AU775736-B2/2001

Gillman G P,Noble A D

Fertilizer for treating soil, includeslayered double hydroxides and/orclay materials

A fertilizer comprises at least one layered doublehydroxide (LDH) compound containing nutrientanion(s) and/or clay material(s) with nutrientcation(s).

Use: For treating soil.

(continued on next page)


Table 1 (continued)


EP987328-A;EP987328-A2;JP2000086694-A;KR2000019408-A;US6329515-B1;KR359716-B/2000

Choy J H,Kwak S Y,Park J S,Choi J H

Bio-inorganic hybrid composite,capable of storing genetic materialfor use in gene therapy andadministering other bio-materials topatients, and its preparation fromlayered double hydroxides

Bio-inorganic hybrid composite (I) forretaining and carrying bio-materials with stabilityand reversible dissociation, obtained bysubjecting a layered double hydroxide to an ionexchange reaction with a bio-material, is new.

Use: (I) are useful in the administration ofgenetic material and other bio-material to apatient such that the bio-material can be safelycarried, and released as required by alteringthe pH of the environment.

US5730951-A/1998 Cedro V,Horn W E,Stinson J M,Martin E S

Preparation of polyvalent inorganicion-intercalated hydrotalcite(s)—involves reacting trivalent metaloxide(s) with divalent metalcompound(s) in carboxylate-freesuspension and contacting with ananion source

Layered double hydroxides or hydrotalcites areuseful as acid neutralisers or scavengers,especially for polypropylene and polyethylene,adsorbents for heavy metal anions from wastewaters, stabilising components for other polymersystems (e.g. polyvinyl chloride), flame retarders,smoke suppressors, catalysts, catalyst supportsand viscosity control agents.


Preparation of monovalent organicanion-intercalated hydrotalcite(s)—involves reacting trivalent metaloxide(s) with divalent metalcompound(s) in carboxylate-freesuspension and contacting withorganic anion

A method for preparing a layered doublehydroxide powder (I) comprises: (a) reactingat least one trivalent metal oxide powder withat least one divalent metal hydroxide, oxideand/or carbonate in a carboxylic acid andcarboxylate ion-free, aqueous suspension to forma double hydroxide intermediate; (b) contactingthe double hydroxide with an anion source; and(c) separating the layered double hydroxideproduct from the suspension. Also claimed is amethod for preparing (I) by steps (b) and (c)where the double oxide is meixnerite (ahydrotalcite-like, layered double hydroxide inwhich the intercalated anions are all hydroxyls)and is reacted with the anion source in a carboxylicacid and carboxylate ion-free aqueous suspension.


Preparation of divalent inorganicion-intercalated hydrotalcite(s)—involves reacting trivalent metaloxide(s) with divalent metalcompound(s) in carboxylate-freesuspension and contacting with ananion source

A method is provided for preparing a layereddouble hydroxide containing at least oneintercalated divalent inorganic anion.


Preparation of hydrotalcite(s) usefulas polymer stabilisers, adsorbents forwaste water, catalysts, etc—involvesreacting trivalent metal oxide(s) withdivalent metal compound(s) incarboxylate-free suspension andcontacting with an anion source

The process uses relatively inexpensive, drypowder components and does not depend on theuse of any alumina gels. The process may yieldno by-products other than water so that conta-mination of (I) with sodium ions is minimisedand any discharge waters are easily disposedof due to their low dissolved solids content.

US5626762-A/1997 Mcculloch B,Priegnitz J W

Separation by simulated moving bedchromatography using a weaklyinteracting adsorbent as the stationaryphase and a liquid mobile phase oflow retention capacity

An improvement in a process for the separationof at least one material from a mixture oforganic materials by simulated moving bedchromatography using as a solid stationary phase,a weakly interacting adsorbent selected from


Table 1 (continued)


silica, alumina, titania, magnesia and layereddouble hydroxides. The improvement compriseseffecting the separation using a liquid mobilephase, which provides a good retention capacity.

Use: In commercial scale preparativeseparations, e.g. of diastereomeric steroids.

EP786984-A;WO9616634-A;WO9616634-A1;AU9642545-A;US5641813-A;ZA9510181-A;EP786984-A1;BR9509849-A;US5786381-A;JP10510274-W/1996

Franklin K R,Houghton S M,Lyle I G

Cosmetic composition comprisinglayered double hydroxide(s) and/orhydroxy salts—for delivering benefitagents e.g. vasodilators, anti-microbial, moisturising and anti-inflammatory agents to skin

The hydroxy material may be used to deliverbeneficial agents to the skin e.g. vasodilators,inhibitors of melanogenesis, anti-ageing,anti-microbial, moisturising, anti-acne,anti-inflammatory and anti-seborrhoeic agents,partic. (i) anti-ageing agents selected from lacticacid, glycolic acid, -hydroxycaprylic acid,lactates, glycolates, acyl lactylates and/or acylglycolates, and (ii) the antimicrobial 2,4,4′-trichloro-2-hydroxy diphenyl ether (triclosan).

US2003049189-A1/2003 Stamires D,Jones W

Preparation of magnesium-containing non-aluminum anionicclay, for use in cosmetics, involvesreacting suspension of trivalent andmagnesium containing divalent metalsources, to form clay havinginterlayers of anions

Preparation of magnesium-containing,non-aluminum clay comprises reacting mixturecomprising aqueous suspension of trivalent metalsource and magnesium-containing source asdivalent metal source.

Use: The method is used for producingmagnesium-containing non-aluminum anionicclays (claimed) which are used in production ofcatalysts, absorbents, pharmaceuticals,cosmetics, detergents and other commodityproducts that contain anionic clays.

US2003031623-A1;US6815389-B2/2003

Stamires D,Brady M F,Jones W,Kooli F

Preparation of anionic clays used as,e.g. catalysts, adsorbents, and drillingmuds, comprises reacting aluminumand magnesium sources in aqueoussuspension to obtain anionic clay

Anionic clays are produced by reactingaluminum (Al) and magnesium (mg) sources inaqueous suspension to obtain the anionic clay.The Al source has 2 types of Al-containingcompounds in which 1 of the types is aluminumtrihydrate or its thermally treated form.

Use: The method is used to prepare anionicclays useful as catalysts, adsorbents, drilling muds,catalyst supports and carriers, and extenders.These are also useful in medical field particularlyin sulfide compounds abatement chemistry.

WO2003078055-A;EP1385622-A;US2003003035-A1;WO2003078055-A1;EP1385622-A1;BR200209531-A;AU2002367444-A1;KR2004012804-A;CN1527743-A;US6903040-B2;JP2005519833-W;IN200301757-P4/2003

Stamires D,O'Connor P,Laheij E J,SonnemansJ W M,Oconnor P,Sonnemans J W

Inorganic solid particle conversionfor catalyst or adsorbent, involvesdispersing sand particles in liquid andpassing suspension throughconversion vessels connected inseries

Amorphous sand particles are dispersed in aliquid to form a suspension. The suspension ispassed through a series of conversion vessels(3A-3D) in which the suspension is agitatedusing a mixer (5) rotated at a speed of 20–500 rpm,to convert the sand particles into product particlesused as catalyst, carrier or adsorbent.

Use: Used for converting inorganic solidparticles, e.g. aluminum oxides or hydroxidessuch as bauxite, crystalline aluminumtrihydrate(ATH), gibbsite, bauxite ore concentrate (BOC)or thermally treated form such as calcined and/or



Table 1 (continued)


flash-calcined forms, synthetic and natural clays,such as kaolin, sepiolite, hydrotalcite or bentonite,silica ores, such as sand or diatomaceous earth,magnesium sources, such as magnesium salts,oxides or hydroxides e.g. brucite, magnesiumcarbonate, magnesium hydroxy carbonate,zirconium compounds such as zirconia, zircon orbaddeleyite, titanium oxides or hydroxides, in toproduct particles for use as a fluidized catalyticcracking (FCC) catalyst, hydroprocessing catalyst(HPC), automotive exhaust catalyst or sorbents etc.,carriers, adsorbents, fillers, electronic material, orfor nano-technological application. Also used forthe production of highly crystalline zirconia byrecrystallization of zirconia ores, e.g. zircon orbaddeleyite and production of zirconia based solidsuper acids. Also for the production of gels suchas aluminum phosphate gels, Al-containingcogels e.g. Al-Zr cogel, Al-Ti cogel or Al-Si cogeletc. Also used for preparation of anionic clay suchas Mg-Al anionic clays that are hydrotalcite andmeixnerite.

WO200268329-A;EP1358128-A;US2002110520-A1;WO200268329-A1;US6593265-B2;EP1358128-A1;KR2003074775-A;BR200207075-A;JP2004522686-W;CN1527799-A;EP1358128-B1;DE60205867-E;ES2248537-T3/2003

Stamires D,Jones W,Daamen S

Preparation of crystalline anionicclay involves aging aqueousprecursor mixture containingaluminum trihydrate or its thermallytreated form and magnesium sour

Providing a method for preparing anionic claywhereby the method does not require washing ofthe product or filtering, thereby reducing filtratewastes, making the process particularlyenvironmentally friendly.

Use: For preparing a 3R1-type crystallineanionic clay, useful in catalysts, adsorbents,drilling mud, catalyst supports and carriers,extenders, and for medical applications.

US6440888-B1/2002 Stamires D,Jones W

Preparation of aluminum-containingnon-magnesium anionic clay, forforming microspheres, comprisesreacting a suspension havingaluminum trihydrate or its thermallytreated form as an aluminum sourceand a divalent metal source

Process for the preparation of an aluminum-containing non-magnesium anionic claycomprises reacting a suspension of an aluminumsource, that is aluminum trihydrate or itsthermally treated form, and a divalent metal source,that is not a magnesium source to obtain the clay.

Use: For preparation of an aluminum-containingnon-magnesium anionic clay which formsmicrospheres or shaped articles. The anionic claycan be combined with other ingredients in themanufacture of catalysts, absorbents,pharmaceuticals, cosmetics, detergents and othercommodity products that contain anionic clays.

US6376405-B1/2002 Stamires D,Brady M F,Jones W,Kooli F

Preparation of anionic clays involvesreacting aluminum sourcecomprising aluminum trihydrate orits thermally treated form, andmagnesium source in aqueoussuspension at preset temperature andpressure

An aluminum source and a magnesium source arereacted in an aqueous suspension maintainedabove 100 °C and above atmosphericpressure, to obtain an anionic clay (I). The alumi-num source comprises two types of aluminumcontaining compounds, where one type isaluminum trihydrate or its thermally treated form.


Table 1 (continued)


Use: (I) can be combined with other ingredientsin the manufacture of catalysts, absorbents,pharmaceuticals, cosmetics, detergents, andother commodity products.

US6333290-B1/2002 Stamires D N,Brady M F,Jones W,Kooli F

Economically and environmentallyfriendly process for synthesis ofanionic clays with acetate anions ascharge-balancing interlayer species

Anionic clays are prepared by reacting a slurrycomprising aluminum trihydrate or its thermallytreated form with a magnesium source andmagnesium acetate.

Use: For producing anionic clays for use ase.g. catalysts, adsorbents, drilling muds, catalystsupports and carriers, extenders and applicationsin the medical field.

WO200138278-A;WO200138278-A1;AU200117086-A;ES2159259-A1;ES2159259-B1/2001

Corma Canos A,Climent Olmedo M J,Velty A I L,Iborra Chornet S,Susarte Rogel M

Selective production of alpha,beta-unsaturated carbonyl compounds,e.g. for use as perfumes, comprisesaldol condensation over easilyrecovered solid alkaline earth metaloxide or mixed oxide catalyst

Selective production of alpha,beta-unsaturatedcarbonyl compounds, by direct aldol conden-sation of an alkyl or alkenyl aldehyde with ashort-chain aldehyde or ketone component, iscarried out in the presence of a solid basic catalystselected from: (a) alkaline earth metal oxideshaving a specific surface of more than 60 m2/g,and (b) mixed di/trivalent metal oxides obtainedby calcining anionic clays at 300–700 °C.

Use: (I) have characteristic organolepticproperties and are useful in perfumery or foodadditive applications, e.g. as fragrances, essencesor aromas. (I) are also useful as precursors forother essences; and include the vitamin Aintermediate pseudoionone.

WO200044672-A;WO200044672-A1;US2003087750-A1;US6800578-B2/2000

Stamires D,Brady M,Jones W,O'Connor P,O'Connor P

Preparation of anionic clays, useful inmanufacture of e.g. catalysts,pharmaceuticals or detergents,comprising hydrothermal treatmentof slurry comprising boehmite whichhas been peptized by inorganic acidand magnesium source

Preparation of anionic clays compriseshydrothermally treating a slurry comprisingboehmite which has been peptized using aninorganic acid and a magnesium source.

Use: The anionic clay is useful in preparation ofa Al-Mg-containing solid solution and/or spinelby subjecting the anionic clay to a heat-treatmentat 300–1200 °C (claimed). Anionic claysare useful e.g. as catalysts, adsorbents, drillingmuds, catalyst supports or carriers, extenders,medical materials and especially in SOxabatement chemistry.

WO200044671-A;EP1152981-A;WO200044671-A1;EP1152981-A1;CN1337920-A;JP2002535234-W;US6541409-B1;EP1152981-B1;DE60021353-E;ES2245934-T3;DE60021353-T2/2000

Stamires D,Brady M,Jones W

New process for the preparation ofanionic clays comprising reacting aslurry comprising boehmite andmagnesium source which is nothydromagnesite

A new process for the preparation of anionicclays comprises reacting a slurry comprisingboehmite and magnesium source which is nothydromagnesite.

Use: The anionic clay is useful in preparationof a Al-Mg-containing solid solution and/or spinelby subjecting the anionic clay to a heat-treatmentat 300–1200 °C (claimed). Anionic clays areuseful in the manufacture of catalysts, absorbents,pharmaceuticals, cosmetics, detergents, and othercommodity products.



Table 1 (continued)


EP982270-A;EP982270-A1;NL1009934-C2/2000

Schmets G H F,Peters F J M L,Kroon E G A,Gielgens L H,Fischer H

New anionic clays useful forstabilizing polymers such aspolyvinyl chloride contain divalentmagnesium, zinc, calcium or iron,trivalent aluminum, iron, cobalt orchromium, and carboxylate anions

New anionic clays contain divalent magnesium,zinc, calcium or iron, trivalent aluminum, iron,cobalt or chromium, and carboxylate anions

Use: The anionic clays are used as stabilizers forpolymers (claimed), especially chlorine-containing polymers such as vinyl polymers, orothers in which acidic residues are present(e.g. polymers prepared through acid catalysis).

WO9941198-A;EP1054838-A;WO9941198-A1;EP1054838-A1;JP2003524569-W;EP1054838-B1;DE69919330-E;DE69919330-T2/1999

Stamires D,Brady M,Jones W,Kooli F

Continuous product of anionic claycompositions used in detergents,catalysts, pharmaceuticals, cosmeticsand absorbents

Continuous preparation of anionic clays fromaluminum trihydrate or its thermally treated formand magnesium sources and production ofaluminum–magnesium solid solution or spinel byheat treatment of this product.

Use: The product can be combined with otheringredients in the manufacture of catalysts,absorbents, pharmaceuticals, cosmetics, detergentsand other commodity products. Anionic clays areknown to be used in catalysts, adsorbents, drillingmuds, catalyst supports and carriers, extendersand in medical applications.


active phases of sensors for the recognition of calciumions. Hence, the biopolymer–Zn–Al nanocompositeshave been incorporated in carbon paste or PVC matrixesfor the development of potentiometric sensors. Thesedevices were applied to calcium determination by directpotentiometry, and the best results were obtained for thesensors based on alginate–LDH and l-carrageenan–LDHnanocomposites.

7. Beneficial effects upon public health

In the last years, many patents related to health andbased on layered double hydroxides have been dev-eloped. The influence of these materials in day-to-daylife is important. Layered double hydroxides becomea promising group of materials to face interestingapplications in numerous fields. Table 1 summarizesthe presence of these materials in different types offormulations that make them an important source ofresearch.

8. Conclusions

Layered double hydroxides can be used in a widerange of applications in health. LDHs are being used asexcipients and active principles in the pharmaceuticalindustry. Development of new pharmaceutical formula-tions is observed, based on layered double hydroxides,for cancer therapy. These laminar solids are revealed as

good excipients for antiinflammatory drugs in formula-tions of controlled release as well as in solar protectors.The importance in the synthesis of biosensors is alsoemphasized. Layered double hydroxides can be consid-ered a group of promising materials in the developmentof new health applications.

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Layered double hydroxides and human health: An overview

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