Asymmetric poly(ethylene glycol)-b-polylactide-b-poly(ethylene glycol) triblock copolymer micelles for dual delivery of paclitaxel and cisplatin: in vitro release, degradation, and biological evaluation

Recent advances in polymeric nanocarriers have highlighted the potential of amphiphilic block copolymers for the simultaneous delivery of chemotherapeutic agents with different physicochemical properties. In this study, asymmetric poly(ethylene glycol)-b-polylactide-b-poly(ethylene glycol) (PEG- b -PLA- b -PEG) triblock copolymers were synthesized via ring-opening polymerization, end-group functionalization, and click coupling, and subsequently evaluated as biodegradable nanocarriers for the co-delivery of paclitaxel (PTX) and cisplatin (CDDP). The copolymers were characterized by 1 H nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). Self-assembly in aqueous media yielded spherical micelles with uniform size distributions, as confirmed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The micelles exhibited efficient encapsulation of PTX and CDDP with high drug-loading capacities and encapsulation efficiencies. Hydrolytic degradation studies conducted at 37 °C for 45 days revealed progressive cleavage of the ester bond, reduction in molecular weight, and gradual disintegration of the micellar structure. In vitro release studies of single- and dual-drug-loaded micelles demonstrated sustained release of both drugs over time. Analysis of the release data using the Korsmeyer–Peppas model provided insight into the release behavior and suggested contributions from both diffusion and polymer degradation processes. The biocompatibility of the unloaded triblock copolymer micelles was assessed through cytocompatibility, hemocompatibility, and zebrafish embryo assays, which indicated low intrinsic toxicity and minimal hemolytic activity. Collectively, these results demonstrate that PEG- b -PLA- b -PEG triblock copolymer micelles can be recognized as biodegradable carriers capable of dual-drug encapsulation and sustained release, providing a useful platform for further investigation of combination drug delivery systems. Graphical abstract Asymmetric PEG- b -PLA- b -PEG triblock copolymers were synthesized and self-assembled into uniform micelles capable of co-encapsulating Paclitaxel and Cisplatin. The micellar architecture provided controlled degradation and synchronized dual-drug release over 45 days. The combination of tunable structure, sustained release, and excellent biocompatibility highlights these triblock copolymer micelles as efficient nanocarriers for combinational cancer therapy