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

• Published in: Pharmaceutical research 2014-05, Vol.31 (5), p.1106-1119
• Main Authors: Mendes, Lívia Palmerston, Gaeti, Marilisa Pedroso Nogueira, de Ávila, Paulo Henrique Marcelino, de Sousa Vieira, Marcelo, dos Santos Rodrigues, Bruna, de Ávila Marcelino, Renato Ivan, dos Santos, Lílian Cristina Rosa, Valadares, Marize Campos, Lima, Eliana Martins
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Blood Vessels - metabolism; Cells; Chromatography, High Pressure Liquid; Drug Delivery Systems; Genistein - administration & dosage; Genistein - therapeutic use; Male; Medical Law; Mice; Microscopy, Electron, Transmission; Nanoparticles; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - pathology; Paclitaxel - administration & dosage; Paclitaxel - therapeutic use; Pharmacology/Toxicology; Pharmacy; Research Paper; Tumors
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-013-1234-x

ABSTRACT Purpose 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. Method 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. Results Entrapment efficiency for both drugs in the nanoparticles was approximately 98%. Average particle diameter was 150 nm with a monomodal distribution. In vitro assays showed distinct temporal drug release profiles for each drug. The dose of 0.2 mg/kg/day of PTX resulted in 11% tumor inhibition, however the association of 12 mg/kg/day of GEN promoted 44% tumor inhibition and a 58% decrease in VEGF levels. Conclusions 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.