Abstract

Stimuli-responsive drug delivery systems are urgently required for injectable site-specific delivery and release of drugs in a controlled manner. For this purpose, we developed novel pH-sensitive, biodegradable, and antimicrobial hydrogels from bio-macromolecule pectin, polyvinylpyrrolidone (PVP), 3-aminopropyl (diethoxy)methyl silane (3-APDEMS), and sepiolite clay via blending and solution casting technique. The purified sepiolite (40 um) was functionalized with 3-APDEMS crosslinker (ex-situ modification) followed by hydrogels fabrication. FTIR and SEM confirmed crosslinked structural integrity and rod-like morphology of hydrogels respectively. The swelling properties of hydrogels could be controlled by varying the concentration of modified clay in pectin/PVP blends. Moreover, the decrease in pH increased the swelling of hydrogels indicating the pH-responsiveness of hydrogels. All hydrogels were degraded after 21 days in phosphate buffer saline pH 7.4 (human blood pH). In-vitro cytotoxicity against 3T3 mouse fibroblast cell line analysis confirmed cytocompatibility of all hydrogels. Ceftriaxone sodium (CTX-S) was selected as a model drug. The release profile of the hydrogel showed 91.82% release in PBS for 2 h in a consistent and controlled manner. The chemical structure of the drug remained intact during and after release confirmed through UV-Visible spectroscopy. Overall, these hydrogels could be used as potential scaffolds for future biomedical applications.

Highlights

  • Conventional methods of drug delivery lead to the diffusion of drugs evenly throughout the body causing considerable damage to normal cells while reducing bioavailability

  • The drug release pattern of ceftriaxone sodium (CTX-S) was investigated in phosphate buffer saline (PBS), simulated gastric fluid (SGF), and simulated intestinal fluid (SIF) via UV-vis spectroscopy

  • Reported method has been followed to modify sepiolite clay with 3-APDEMS (Shafiq et al, 2012). 3-APDEMS was used as the characteristic bifunctional crosslinker; its silanol groups reacted with -OH of sepiolite during modification and -NH2 with polymer matrix during hydrogel fabrication via condensation

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Summary

INTRODUCTION

Conventional methods of drug delivery lead to the diffusion of drugs evenly throughout the body causing considerable damage to normal cells while reducing bioavailability. Polymeric chains crosslink to develop microporous three-dimensional semi-interpenetrating networks (semi-IPNs) called hydrogel by penetrating at least one suitable linear or branched polymer (Liu et al, 2003; Mishra et al, 2008; Sivagangi Reddy et al, 2016; Rinoldi et al, 2021) Polysaccharides and their derivatives are among the ideal candidates for smart hydrogel formation due to stimuli-responsive behavior, reducing dose frequency, nontoxicity, stability, biocompatibility, biodegradability, easy availability, and cost-effectiveness (Roy et al, 2010; Sharma and Ahuja, 2011). According to the best of our knowledge, the modification of sepiolite with 3-APDEMS, development of pectin/PVP/modified clay based hydrogels and their use for the delivery and controlled release of ceftriaxone sodium (CTX-S) has not been reported yet. The drug release pattern of CTX-S was investigated in phosphate buffer saline (PBS), simulated gastric fluid (SGF), and simulated intestinal fluid (SIF) via UV-vis spectroscopy

Materials
Modification of Sepiolite With 3-APDEMS
Fabrication of Hydrogels
Swelling Studies
FTIR Analysis
In-vitro Degradation
Antimicrobial Analysis
Cytotoxicity Studies
2.10 Ceftriaxone Sodium (CTX-S Antibiotic Drug) Loading and Release Analysis
2.11 Chemical Activity
RESULTS AND DISCUSSION
FTIR Analysis of Functionalized Sepiolite
Morphological Analysis of Hydrogels via SEM
Swelling Response of Hydrogels in Water
Effect of pH on Swelling of Hydrogels
Effect of Ionic Concentration on Swelling of Hydrogels
Release Analysis of CTX-S
Chemical Activity
CONCLUSION
DATA AVAILABILITY STATEMENT
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