Biocompatible HA-PBA/PVA Dual-Network Hydrogel Composite System: A Promising Localized Therapeutic Platform for Bladder Cancer.

Abstract

Bladder cancer is among the most common malignancies of the urinary system and is characterized by high recurrence rates and unsatisfactory clinical outcomes. Current therapeutic strategies are limited by inadequate local efficacy, rapid drug loss caused by the bladder microenvironment, and systemic toxicity associated with conventional chemotherapy. In this study, we developed a localized therapeutic platform for bladder cancer based on a hyaluronic acid-phenylboronic acid/poly(vinyl alcohol) (HA-PBA/PVA) dual-network hydrogel incorporating liposomes co-loaded with resveratrol (Res) and gemcitabine (Gem). The hydrogel system was designed to provide sustained local drug delivery and improved intravesical retention. Physicochemical characterization demonstrated favorable injectability, self-healing capacity, mechanical stability, and pH-responsive sustained-release behavior. The embedded liposomes exhibited a uniform nanoscale size distribution and high drug encapsulation efficiency. In vitro studies showed that the composite hydrogel displayed good biocompatibility and significantly inhibited MB49 bladder cancer cell proliferation, induced apoptosis, and suppressed migration and invasion. In vivo evaluation further demonstrated favorable biosafety and enhanced antitumor efficacy of the hydrogel-based local delivery system. These findings indicate that the HA-PBA/PVA hydrogel-liposome composite system is a promising localized therapeutic strategy for bladder cancer.