Transforming docetaxel delivery: lung-targeted polyphosphazene nanoparticles with enhanced safety profile

Abstract

Polyphosphazene–docetaxel conjugate (Polytaxel, PTX) represents a rationally engineered nanomedicine designed to address the limitations of conventional taxane chemotherapy. PTX exhibits improved aqueous solubility, controlled drug release, and favorable NOAEL (no observed adverse effect level) characteristics, making it a promising alternative to free docetaxel (DTX). In this study, we demonstrate that PTX achieves robust anti-tumor efficacy both in vitro and in vivo, while markedly reducing systemic toxicity compared to DTX. In an A549 xenograft mouse model, PTX suppressed tumor growth without inducing weight loss or mortality. Furthermore, in vivo metabolic profiling revealed a distinct biodegradation and clearance mechanism, with minimal generation of inactive or toxic metabolites. These results highlight the potential of PTX as a safe and effective drug delivery platform that combines enhanced therapeutic performance with reduced systemic burden, supporting its future clinical translation in cancer chemotherapy.