Biocompatible Hydrogels for Controlled Drug Release

Abstract

Hydrogels -- three-dimensional, water-swollen polymer networks -- are among the most versatile platforms for controlled drug delivery, offering tuneable release kinetics, injectable formulations, and stimuli-responsive behaviour matching diverse therapeutic requirements. This study developed and compared four hydrogel systems -- polyethylene glycol diacrylate (PEGDA) photocrosslinked, hyaluronic acid-tyramine (HA-Tyr) enzymatically crosslinked, alginate-calcium ionically crosslinked, and a thermoresponsive poly(N-isopropylacrylamide)/chitosan (PNIPAAm/CS) composite -- for sustained delivery of three model drugs: doxorubicin (DOX, small molecule chemotherapeutic, MW 543 Da), bevacizumab (BEV, monoclonal antibody, MW 149 kDa), and insulin (peptide, MW 5.8 kDa). Release kinetics over 28 days showed that HA-Tyr hydrogels achieved the most sustained DOX release (t50 = 8.4 +- 0.8 days; Korsmeyer-Peppas n = 0.72) with 84.2 +- 6.4% bioactivity retention, while PNIPAAm/CS provided optimal temperature-triggered pulsatile release (4.2-fold burst at 40degC vs 37degC). PEGDA hydrogels achieved the highest protein stability for bevacizumab (92.4 +- 3.8% binding activity at day 28) due to the inert PEG network minimising protein-polymer interactions. Alginate hydrogels demonstrated the fastest gelation (< 30 s) suitable for injectable depot formulations. In vivo evaluation in a subcutaneous tumour model (4T1 breast cancer, n = 8/group) showed that HA-Tyr/DOX hydrogels reduced tumour volume by 64.8 +- 8.4% versus 42.4 +- 10.2% for free DOX injection (p < 0.001). These results establish a quantitative hydrogel selection framework matching material properties to drug class and therapeutic requirements.