Transcript
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BySayan Ganguly
Synthesis and characterization of multifunctional superabsorbent smart hydrogels
Introduction and Literature Survey
Motivation and Objective
Synthesis of polyethylene glycol/poly(acrylic acid-co-N-vinylpyrrolidone)
composite hydrogel for controlled release of drug
Results and Discussion
Conclusion
Future plan
References
Acknowledgement
Outline
Three-dimensional networks of hydrophilic polymer chains that do not dissolve but can swell in water
High biocompatibility Environmental stimuli responding (temperature, pH, light, specific molecules) Mechanically strong Capable of achieving high drug loading Simple to administer and remove Free of leachable impurities Easy to fabricate and sterilize
Introduction
Hydrogels
1894• First coined the term hydrogel by van Bemmelen
1958• PVA hydrogels via gamma irradiation by Danno
1960• P(HEMA) gel for biological use by Wichterle & Lim
1968• Poly(NIPAM) solution displaying temp. dependent phase transition By Heskins & coworkers
1990• PNIPAM hydrogel via redox initiated polymerization by Otake & Inomata
1995• Natural-synthetic hybrid hydrogels by Cascone et al.
1997• Temperature responsive PEG-PLA hydrogels by Jeong et al.
2001• PEG hydrogels via Michael addition by Elbert et al.
2006• PEG hydrogels via click chemistry by Ossipov et al.
Literature Reviews
2010• Age of smart hydrogels begins with hybrid fillers
2010• Graphene oxide/PVA hydrogels for controlled release by Bai et al.
2012• Drug delivery from PHPMC matrix by Peppas et al.
2014• pH-responsive poly(itaconic acid-co-vinylpyrrolidone) hydrogel by Peppas et al.
2016• Shape memory acrylamide-DNA hydrogel by Hu et al.
Cond…
J. Mat. Chem. B, 3.18, 2015, 3654-3676.
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Drug delivery, scaffolds, food preservation, biosensors Study cell and tissue physiology Large water content and rubbery consistency makes hydrogels great
mimics for living tissue
Scope and motivations
Scope and motivations
Aim is to develop a high swelling hydrogel based on Poly(AA-co-NVP) copolymer hydrogel which is a vehicle for drug release in controlled fashion.
Sequential semi-IPN based on this polymer can enhance gel strength and better swelling in psychological pH.
Developing hydrogel with withstanding drastic pH fluctuations.
Sustained release:
Any dosage form that provides medication over an extended time
Timed release, prolonged release etc.
Controlled release:
Denotes that the system is able to provide some actual therapeutic control, whether this be of a temporal nature, spatial nature, or both
Terminology
With traditional administration, the drug active must remain between a maximum blood level value which may represent a toxic level and a minimum value below which the drug is no longer effective
With controlled administration, the blood levels are constant between the desired maximum and minimum for an extended period of time
Traditional vs. Controlled Release Drug Dosing
Origin Natural
Synthetic
Water content or degree of swelling Low swelling
Medium swelling
High swelling
Superabsorbent
Porosity Nonporous
Microporous
Macroporous
Superporous
Cross-linking Chemical (covalent bonding)
Physical (non-covalent bonding)
Biodegradability Biodegradable
Nondegradable
Classification of hydrogels on account of various criteria
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Chemical hydrogels Physical hydrogels
▪ Hydrogen bonding
▪ Hydrophobic interaction
▪ Crystallinity
▪ Stereocomplex formation
▪ Ionic complexation
Covalently crosslinked Noncovalently crosslinked
Thermoset hydrogels Thermoplastic hydrogels
Volume phase transition Sol-gel phase transition
Reliable shape stability and memory
Limited shape stability and memory
Hydrogel Fabrication
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Polymerization of water soluble monomers in the presence of bi- or multifunctional cross-linking agent
+
Monomer Crosslinker
Vinyl group-containing water-soluble polymers
Copolymerization
Polymerization
Hydrogel network
or
Chemical crosslinking
Hydrogel Fabrication
One self-made study: Reaction Scheme for hydrogel preparation
Ref: Ganguly, Sayan, and Narayan C. Das. "Synthesis of a novel pH responsive phyllosilicate loaded polymeric hydrogel based on poly (acrylic acid-co-N-vinylpyrrolidone) and polyethylene glycol for drug delivery: modelling and kinetics study for the sustained release of an antibiotic drug." RSC Advances 5.24 (2015): 18312-18327.
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XRD and SEM study
XRD of pristine PEG and hydrogel
SEM image of porous structure
of hydrogel
SEM image ofFiller loaded
hydrogel
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pH reversibility (switch on-off behavior) of the gels Sw
ell R
atio
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Yield% =
Gel% =
Sol% = 100 – Gel%
Rs= Rs= swelling ratioWs = weight of swollen hydrogelsWd = weight of dried hydrogels
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Effect of reaction variables on synthesis
Effect of medium salinity and pH
Concentration(M) pH
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Effect of reaction variables
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Gel time (m
in)
Gel time (m
in)
Swel
l rati
o
Gel time (m
in)
Swel
l rati
o
Swel
l rati
o
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1st order swelling kinetics: SRt=
Swelling kinetics study of hydrogels
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Case I
Anomalous
Case II
Mechanism behind swelling
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De-swelling of hydrogels
Free water
Interstitial water
Bound water
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Formation of hydrogel and drug loading
x
xComplexed Small
mesh size low pH
Uncomplexed
Increased mesh
size high pH
H2C C
CH3
C O
O-
H2C C
CH3
-OOC
Protect drug
Release drug
Complexation and pH responsive hydrogels
Stomach pH ~2
H2C C
CH3
C O
H2C C
CH3
HOOCHO
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Drug release and Peppas model
𝑭 𝑫=𝒎𝑫𝒕
𝒎𝑫𝒆=𝑲𝑲𝑷 𝒕𝒏
mDt amount of drug released at time tmDe are and infinity (at equilibrium)KKP = Peppas constantn = drug release exponent
n
0.5 1.0
0.5 – 1.0Case I
Anomalous transport
Case II
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