Rational design of paclitaxel prodrugs for facile preparation of in-situ therapeutic system in antitumor applications

Abstract

This study introduces a novel theoretical framework for designing paclitaxel (PTX) prodrugs, emphasizing the potential of hydrogel-encapsulated agents for in situ delivery. Despite paclitaxel's common use in chemotherapy, its clinical application is constrained by low aqueous solubility, hindering effective hydrogel formulations. We developed a simple yet efficient PTX-encapsulating hydrogel and synthesized various PTX prodrug derivatives, examining their self-assembly behaviors. The optimized hydrogel system demonstrated excellent therapeutic efficacy and minimal side effects in anti-tumor studies, with validation across multiple animal models. This research not only lays a foundation for PTX formulation design but also paves the way for its clinical application, underscoring our contributions to drug delivery.