Pharmaceutics IV Novel DRUG DELIVERY SYSTEMS 2
Pharmaceutics IVNovel DRUG DELIVERY SYSTEMS 2
Contents
• Drug delivery• Targeted drug delivery• Nanotechnology• F i e l d s u s i n g n a n o t e c h n o l o g y• Dendrimers• Applications in drug delivery (dendrimers)• Mechanism of drug delivery (dendrimers)• Liposome• Liposomes in drug delivery• Liposome preparation• Micelle• Micellar shape• Micelle formation mechanism• Miclle as drug carrier
Drug Delivery
• Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect.
• Drug delivery technologies that modify Drug release profiles Absorption Distribution Elimination
for the benefit of improving product efficacy and safety and patient convenience and compliance.
Drug Delivery
Most common methods of delivery include the
•Non-invasive peroral (through the mouth)•Topical (skin)•Transmucosal (nasal, buccal/sublingual, vaginal,
ocular and rectal) • Inhalation routes. •Parental (IV, IM, IA, ISp etc)
Generation of Drug Delivery System
1st Generation 2nd Generation
3rd Generation
4th Generation
5th Generation
Tablet
Capsule
Ointment
Suspension
Emulsion
Suppositories
Repeat action tablet
Prolonged action tablet
Enteric Coated tablet
Timed Release tablet
Osmotically Control System
Swelling Controlled
Magnetic Controlled System
Diffusion Controlled System
Targeted DDS
Modulated DDS
Self Regulated DDS
Gene Therapy
TARGETED DRUG DELIVERY
Targeted drug delivery, sometimes called smart drug delivery
•A method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others.
•The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue.
Advantage of targeted drug delivery system over traditional drug delivery
system•Increased efficacy of the drug.•Site specific delivery.•Decreased toxicity/side effects.•Increased convenience.•Better patient compliance.•Viable treatments for previously
incurable diseases.
Novel drug delivery system
It is advance drug delivery system which improve
•Drug potency•Control drug release to give a sustained
therapeutic effect•Provide greater safety•Finally it is to target a drug specifically to
a desired tissue
“Nanotechnology is the art and science ofmanipulating matter at the nanoscale”
which is about 1 to 100 nanometers.
Nanotechnology
1.Medicine2.Energy i) Reduction of energy consumption ii) Increasing the efficiency of energy production iii) The use of more user friendly energy systems
3.Information and Communication4.Heavy Industries i) Aerospace ii) Refineries iii) Vehicle manufactures
Fields using Nano Technology
NANOTECHNOLOGY IN MEDICINE
DRUG DELIVERY THERAPY TECHNIQUES ANTI – MICROBIAL TECHNIQUES DIAGONISTIC TISSUE ENGINEERING
NANOTECHNOLOGY IN MEDICINE
DRUG DELIVERY - Employing nanoparticles to deliver
drugs. - Oral administration of drugs.
NANOTECHNOLOGY IN MEDICINE
THERAPY TECHNIQUES - Buckyballs - Nanoshells - Nanoparticles - Aluminosilicate Nanoparticles - Nanofibers
ANTI-MICROBIAL TECHNIQUES - Nanoparticle Cream - Nanocapsules
- Cell repairs using Nanorobots
NANOTECHNOLOGY IN MEDICINE
i) Nanotechnology-on-a-chip is one more dimension of lab-on-a-chip technology.
ii) Magnetic nanoparticles, bound to a suitable antibody, are used to label specific molecules, structures or microorganisms.
i i i ) Go ld nanoparti c les tag ged with short segments of DNA can be used for detecti on of geneti c sequence in a sample .
DIAGNOSTICS
i) Nanotechnology can help to reproduce or to repair damaged tissue.
ii) “Tissue engineering” makes use of artificially stimulated cell proliferation by using suitable nanomaterial-based scaffolds and growth factors.
iii) Tissue engineering might replace today’s conventional treatments like organ transplants or artificial implants. Advanced forms of tissue engineering may lead to life extension.
TISSUE ENGINEERING
Applications of Nanoparticles to Drug Discovery and Biology• Fluorescent biological markers• Detection of proteins• Probing of DNA structures• MRI contrast enhancement• Separation and purification of biological
molecules and cells• Tumor destruction via heating• Tissue engineering• Drug and gene delivery
Possible Opportunities for Nanotechnology in Drug Delivery
Enhanced drug properties such as:▫Solubility ▫Rate of dissolution▫Oral bioavailability▫Targeting abilityEnhanced dosing requirements:
Lower dosed administeredBetter side effect profileMore convenient dosage forms
FDA-Regulated Products Expected to be Impacted by Nanotechnology•Drugs (delivery systems)•Medical devices•Biotechnology products•Tissue engineering products•Vaccines•Cosmetics•Combination products
•Tree-like polymers, branching out from a central core and subdividing into hierarchical branching units
- Not more that 15 nm in size, Mol. Wt very high
- Very dense surface surrounding a relatively hollow core (vs. the linear structure in traditional polymers)
Dendrimers
In 2008 there were over 10 000
scientific reports and 1000 patents
dealing with dendritic structures.
Courtesy of: http://www.uea.ac.uk/cap/wmcc/anc.htm
Dendrimers
Dendritic Family
Structural Components of Dendrmers
drugs
drug delivery – Small molecules Proteins Tissue targeting
Drug solublization
RNA/DNA delivery
Diagnostics & materials applications
Applications in Pharmaceutical Industry
Improved efficacy of drugs Extension of drug half-life Reduced toxicity Active or passive targeting Product lifecycle
management Improved solubility of drugs Drug “rescue”
Applications in Drug Delivery
Utilizing a dendrimer construct the aqueous solubility of the drug Paclitaxel was increased >9,000X.
Paclitaxel aqueous solubility 0.8 mg/mL
Improved Drug Solubility
•Dendrimers are particularly attractive as they offer a high drug-loading capacity.
•2 methods of dendrimer drug delivery are Encapsulation of drugsDendrimer –drug conjugates
Mechanism of drug delivery: Dendrimer
•Interactions between the dendrimer and drug to trap the drug inside the dendrimer.
Such a system can be used to encapsulate drugs and provide controlled delivery.
• ,eg: DNA was complexed with PAMAM dendrimers for gene delivery applications, and hydrophobic drugs and dye molecules were incorporated into various dendrimer cores.
Mechanism of drug delivery: Dendrimer
Dendrimer–Drug Conjugates In dendrimer–drug conjugates, the drug is attached through a covalent bond either directly or via a linker/spacer to the surface groups of a dendrimer.
Dendrimers have been conjugated to various biologically active molecules such as drugs, antibodies, sugar moieties and lipids
Mechanism of drug delivery: Dendrimer
The drug loading can be tuned by varying the generation number of the dendrimer
Release of the drug can be controlled by incorporating degradable linkages between the drug and dendrimer
Conjugates of PAMAM dendrimers with cisplatin, a potent anticancer drug with non-specific toxicity and poor water solubility.
The conjugates show increased solubility, decreased systemic toxicity and selective accumulation in solid tumors
Mechanism of drug delivery: Dendrimer
Drugs Delivered Through Dendrimers
Phospholipids
Polar Head Groups
Three carbon glycerol
An artificial microscopic vesicle consisting of an aqueous core enclosed in one or more phospholipid layers.
Used to convey vaccines, drugs, enzymes, or other substances to target cells or organs.
Liposome
Liposome
▫Spherical vesicles with a phospholipid bilayer
Hydrophilic
Hydrophobic
Liposomes can be subcategorized
• Small unilamellar vesicles (SUV), 25 to 100 nm in size that consist of a single lipid bilayer
• Large unilamellar vesicles (LUV), 100 to 400 nm in size that consist of a single lipid bilayer
• Multilamellar vesicles (MLV), 200 nm to several microns, that consist of two or more concentric bilayers
• Vesicles above 1 µm are known as giant vesicles.
1. Conventional Liposomes
▫Prepared form natural neutral and anionic lipids and have nonspecific interactions with their environment
▫Relatively unstable▫Have low carrying capacities▫ Tend to be “leaky” to entrapped drug substances .
Types of Liposomes
• Non-conventional Liposomes
▫Small sized, surface modified to overcome some of the short comings of conventional liposomes
▫Modified to reduce negative charge, decrease fluidity and cause steric hinderance to phagocytosis
▫Properties altered (e.g. by incorporation of cholesterol) ▫Polymerized liposomes more stable and less “leaky”
Types of Liposomes
Uses of Liposomes
Chelation therapy for treatment of heavy metal poisoning
Enzyme Replacement Diagnostic imaging of tumors
Study of membranes
Cosmetics
Drug Delivery
•They can deliver agents directly into cells.
•Routes:• Intravenous (iv)• Subcutenuous (sc)• Intramuscular (im)• Topical• Pulmonary
Route of Liposomes in Drug Delivery
•Improved therapeutic response ▫Achieve appropriate tissue or blood levels
•Reduced adverse reactions ▫Less drug administered ▫Targeted drug release
•Lower dosing frequency ▫Improved patient compliance ▫Simpler dosing regimens ▫Lower cost per dose
Advantages of Liposomes in Drug Delivery
▫ Doxil Daunorubicin 1995 ▫ Daunoxome Daunorubicin 1996 ▫ Ambisome Amphotericin B 1997 ▫ Depocyt Cytarabine 1999
APPROVED LIPOSOME PRODUCTS
Liposome PreparationLipid in organic solvent solution
Evaporation
Extrusion (or sonication)
Liposomes and unencapsulated SRB
Lipid film
Freeze/thaw cycles
Gel filtration
Purified liposomes
Hydrate with sulforhodamine B (SRB) solution
Liposome Preparation
Critical factors in Liposome preparation
•Particle size •Method of manufacture •Lipid types •Polymerization •Interfacial charge •Steric stabilization •Sterilization
Modes of Liposome/Cell Interaction
Adsorption Endocytosis
Fusion Lipid transfer
Media and Methods that can affect Release
•Solvents •pH •Temperature •Agitation •Enzymes •Cell culture •Sink conditions •Volume •Sampling interval
Liposomes Help Improve
Therapeutic indexRapid metabolismUnfavorable pharmokineticsLow solubilityLack of stabilityIrritation
Custom designLipid contentSize
Surface chargeMethod of preparation
Micelle
•Micelles are like tiny balls of molecules.•They are made out of amphipathic molecules.•An amphipathic molecule is a molecule that is Both
hydrophilic (polar) and hydrophobic (non-polar).•A micelle is a ball that forms when amphipathic
molecules are put in a liquid. The liquid can be polar (like water) or non-polar (like butane or octane).
MICELLAR SHAPE
Stepwise growth model (Isodesmic model)
Closed aggregation model
Micelle formation mechanism
Micelle formation mechanism
Stepwise growth model (Isodesmic model)
Aggregation is a continuous process
broad aggregation, no cmc
Closed aggregation model
Aggregation number n dominates
Micelle formation mechanism
OH
H
O
HH
OH
H
Surfactant Micelle
Hydrophilic
Hydrophobic
OH
H
O
HHO
HH
O
H
H
OH
H
OH
H
H2O
Miclle as Drug Carrier
Miclle as Drug Carrier
SUMMARY AND CONCLUSION
- From being a theory to something we can now see, words turned into reality.
- Nanotechnology has evolved over the period of time for many decades, and is now showing its potential to the whole world.
- The development of nanomachines such as: I-switch, nanoimpellers, nanobots etc.
- Nanotechnology will increase your standard of living.- Up to today nanotechnology is what's in, what's new, and
what's the latest technology being developed all over the world.
FOR THE ATTENTION