Effect of molecular weight of PGG–paclitaxel conjugates on in vitro and in vivo efficacy

Polymeric prodrugs are one of the most promising chemotherapeutic agent delivery approaches, displaying unique drug release profiles, serum stability, formulation flexibility, and reduced drug resistance. One of the most important aspects of a polymeric prodrug, albeit a less-extensively studied one, is the polymer's molecular weight, which affects particle formation, drug release and PK/PD profiles, drug stability, and cell uptake; these factors in turn affect the prodrug's maximum tolerated dose and anticancer efficacy. Poly(l-γ-glutamylglutamine) (PGG) is a linear polymer designed to improve the therapeutic index of attached drugs. In this study we selected poly(l-γ-glutamylglutamine)–paclitaxel (PGG–PTX), as a model system for the methodical investigation into the effects of the poly(l-γ-glutamylglutamine) backbone molecular weight on its pharmacological performance. The polymeric prodrug was characterized by NMR, DLS and GPC–MALS, and its anticancer activity in vitro and in vivo was assessed. Herein we present data which provide valuable insight into improving anticancer polymer-based prodrug design and development.

Graphical abstractPoly(l-γ-glutamylglutamine)–paclitaxel was designed to improve the therapeutic index of the parent drug. As a model system we investigated the effects of the backbone molecular weight on its pharmacological performance.Figure optionsDownload full-size imageDownload high-quality image (95 K)Download as PowerPoint slide