May 1, 2023 1

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.

May 1, 2023 6

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

May 1, 2023 10

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

May 1, 2023 11

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.

May 1, 2023 13

XRD and SEM study

XRD of pristine PEG and hydrogel

SEM image of porous structure

of hydrogel

SEM image ofFiller loaded

hydrogel

May 1, 2023 14

pH reversibility (switch on-off behavior) of the gels Sw

ell R

atio

May 1, 2023

Yield% =

Gel% =

Sol% = 100 – Gel%

Rs= Rs= swelling ratioWs = weight of swollen hydrogelsWd = weight of dried hydrogels

15

Effect of reaction variables on synthesis

Effect of medium salinity and pH

Concentration(M) pH

May 1, 2023

Effect of reaction variables

17

Gel time (m

in)

Gel time (m

in)

Swel

l rati

o

Gel time (m

in)

Swel

l rati

o

Swel

l rati

o

May 1, 2023 18

1st order swelling kinetics: SRt=

Swelling kinetics study of hydrogels

May 1, 2023 19

Case I

Anomalous

Case II

Mechanism behind swelling

May 1, 2023 20

De-swelling of hydrogels

Free water

Interstitial water

Bound water

May 1, 2023 21

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

May 1, 2023 23

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