Protein Hydrogels as a Thermoinduced Platform for Controlled Antibiotic Release
Oksana A. Mayorova1, Olga I. Gusliakova1, Valentina O. Plastun1; 1Saratov State University, Saratov, Russia
Abstract
Postoperative infectious complications remain a challenge in surgery due to the limited local bioavailability of systemically administered antibiotics and the associated risk of toxicity. Local prolonged release delivery systems can maintain therapeutic concentrations directly at the wound site, thereby enabling dose reduction and fewer adverse effects. The aim of this study was to develop and comprehensively characterize whey protein isolate (WPI) based hydrogels as a matrix for the controlled release of cefazolin in the treatment of local infections. Experiments revealed that WPI hydrogels exhibited biphasic release kinetics: an initial rapid burst of up to 40% within the first 6 hours, followed by a sustained prolonged release over 72 hours, which significantly outperformed the release profile of free cefazolin. Maximum cumulative concentration was achieved at 48 hours and remained stable thereafter. Furthermore, hydrogel swelling (a 2.1 fold increase in mass) correlated with partial matrix degradation; however, the structure remained intact for the initial 48 hours, which is critical for drug retention at the application site. Antimicrobial activity against S. aureus was assessed both by inhibition zone measurements (18–24 mm depending on concentration) and in liquid culture: hydrogels loaded with 5 and 10 mg/mL cefazolin induced killing of over 60% of the bacterial population within 24 hours, and the effect persisted for at least 48 hours, whereas the activity of free antibiotic dropped by 40% over the same period. Importantly, WPI hydrogels with cefazolin exhibited significantly lower cytotoxicity toward L929 fibroblasts compared to an equivalent dose of the free drug (less than 15% reduction in metabolic activity vs. 35% in the control), confirming the biocompatibility of the system. Thus, the developed hydrogels combine sustained release, robust antimicrobial activity against S. aureus, and low host cell toxicity. Given the availability and safety of WPI, this platform holds promise for clinical application in the local therapy of surgical infections.
This research was funded by the Russian Science Foundation (grant No. 26-74-10068).
Speaker
Oksana A. Mayorova
Saratov State University
Russia
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