Site-Specific Drug Delivery Using Injectable pH-Responsive Biopolymeric Hydrogel: Instant Crosslinking and Shear Thinning

Abstract

Injectable hydrogels provide enhanced targeting capabilities, and their minimally invasive administration makes them promising drug carriers. However, concerns related to biodegradability and biocompatibility may restrict their effectiveness. To overcome these limitations, a pH-responsive, injectable, shear-thinning hydrogel has been developed using modified carboxymethyl cellulose (m-CMC) and modified chitosan (m-CS). The hydrogel has been synthesized by cross-linking the amine groups of m-CS with the aldehyde groups of m-CMC. The resultant hydrogel exhibits rapid gelation within 60 s at physiological temperature and forms a dynamic network through Schiff base and electrostatic interactions, enabling shear-thinning behavior. The incorporation of m-CMC and m-CS into the hydrogel backbone enhances biocompatibility, hemocompatibility, biodegradability, and antioxidant properties. The ease of injectability allows for minimally invasive administration and prolonged drug retention at the target site, thereby improving the efficiency of site-specific drug delivery. Additionally, the hydrogel exhibits potential antibacterial characteristics against Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria. The pH-responsive nature of the m-CMC/m-CS hydrogel enables the controlled release of a model drug (diclofenac sodium, DS) at the target site under physiological conditions, thereby improving therapeutic efficacy.