Phytosomes loaded with mitomycin C-soybean phosphatidylcholine complex developed for drug delivery.

Abstract

A novel formulation system of phytosomes loaded with mitomycin C-soybean phosphatidylcholine (MMC-SPC) complex (MMC-loaded phytosomes) was prepared by a solvent evaporation method combined with a nanoprecipitation technique for the purpose of development of an MMC drug delivery system. The MMC-loaded phytosomes were evaluated by average particle size, zeta-potential, and residual drug-loading content as well as an in vitro drug release profile. Furthermore, in vitro stability tests and in vitro/vivo biological evaluations of the MMC-loaded phytosomes were performed. DSC, FTIR, and XRD demonstrated that MMC interacted physically with SPC within the phytosomes. DLS and ELS described a dispersion with an average particle size of 210.87 nm, a narrow size distribution (PDI 0.251), and a zeta-potential of -33.38 mV. SEM, TEM, and AFM images showed that the MMC-loaded phytosomes were spherical and intact vesicles. In vitro stability tests demonstrated that the average particle size and residual drug-loading content of the MMC-loaded phytosomes had no evident change at different storage conditions. In vitro drug release profiles indicated biphasic behavior with an initial burst release, followed by a subsequent prolonged sustained release. In vitro cytotoxicity assays with H(22) cells showed that the MMC-loaded phytosomes had remarkable cytotoxicity. In vivo antitumor effect of the MMC-loaded phytosomes also revealed a dose-dependent and superior curative inhibitory effect on tumor growth without loss of body weight compared to free MMC. Histopathological analysis of specimens taken from tumor tissues indicated that MMC-loaded phytosomes had lethal effect to hepatoma cell. These findings suggested that the MMC-loaded phytosomes can serve as a promising and effective formulation for drug delivery and cancer therapy.

• Authors: Zhenqing Hou, Yang Li, Yuancan Huang, Chunxiao Zhou, Jinyan Lin, Yixiao Wang, Fei Cui, Shuifan Zhou, Mengmeng Jia, Shefang Ye, Qiqing Zhang
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 10 Issue 1 Pg. 90-101 (Jan 07 2013) ISSN: 1543-8392 [Electronic] United States
• PMID: 23194396 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Phosphatidylcholines
• Solvents
• Mitomycin

Topics

• Animals
• Antineoplastic Agents (administration & dosage, chemistry)
• Cell Line, Tumor
• Chemistry, Pharmaceutical (methods)
• Drug Delivery Systems (methods)
• Drug Stability
• Liver Neoplasms, Experimental (drug therapy)
• Male
• Mice
• Mitomycin (administration & dosage, chemistry)
• Nanotechnology (methods)
• Particle Size
• Phosphatidylcholines (administration & dosage, chemistry)
• Solubility
• Solvents (chemistry)
• Soybeans (chemistry)