Multicompartimental Nanoparticles for Co-Encapsulation and Multimodal Drug Delivery to Tumor Cells and Neovasculature

Abstract

The purpose of this work was the development of a multicompartimental nanocarrier for the simultaneous encapsulation of paclitaxel (PTX) and genistein (GEN), associating antiangiogenic and cytotoxic properties in order to potentiate antitumoral activity. Polymeric nanocapsules containing PTX were obtained by interfacial deposition of preformed polymer and coated with a phospholipid bilayer entrapping GEN. Physical-chemical and morphological characteristics were characterized, including size and size distribution, drug entrapment efficiency and drug release profile. In vivo studies were performed in EAT bearing Swiss mice. Entrapment efficiency for both drugs in the nanoparticles was approximately 98%. Average particle diameter was 150nm with a monomodal distribution. In vitro assays showed distinct temporal drug release profiles for each drug. The dose of 0.2mg/kg/day of PTX resulted in 11% tumor inhibition, however the association of 12mg/kg/day of GEN promoted 44% tumor inhibition and a 58% decrease in VEGF levels. Nanoparticles containing GEN and PTX with a temporal pattern of drug release indicated that the combined effect of cytotoxic and antiangiogenic drugs present in the formulation contributed to the overall enhanced antitumor activity of the nanomedicine.