Preparation of Pixantrone/Poly(γ-glutamic acid) Nanoparticles through Complex Self-Assembly for Oral Chemotherapy

Abstract

A facile and green approach is reported to construct pixantrone/poly(γ-glutamic acid) nanoparticles (PIX/γ-PGA NPs) as an oral drug delivery system through the complex self-assembly of polyelectrolyte γ-PGA and the anticancer drug pixantrone dimaleate (PDM). The complex self-assembly behavior is investigated in detail. The results demonstrate that PDM can interact with γ-PGA to conveniently form NPs and the size of NPs can be controlled by adjusting the solution volume ratio of PDM to γ-PGA. These NPs illustrate their pH-dependent release behavior, efficient cellular uptake and enhanced drug efficacy through an in vitro release study, flow cytometry, CLSM analysis and the MTT assay. In summary, PIX/γ-PGA NPs may serve as a promising oral drug delivery system for cancer therapy. PIX/γ-PGA NPs are prepared by mixing anionic γ-PGA and the anticancer drug PDM in water. They exhibit pH-dependent release behavior under the simulated environment of the gastrointestinal tract. In vitro studies show that PIX/γ-PGA NPs can be effectively internalized by Lovo cancer cells and display potent anticancer efficacy. The IC50 of PIX/γ-PGA NPs is 0.40μgmL-1. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.