Therapeutic Effect of Folate-Targeted and PEGylated Phytosomes Loaded with a Mitomycin C鈥揝oybean Phosphatidyhlcholine Complex

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• 作者：Yang Li ; Hongjie Wu ; Mengmeng Jia ; Fei Cui ; Jinyan Lin ; Xiangrui Yang ; Yange Wang ; Lingfeng Dai ; Zhenqing Hou
• 刊名：Molecular Pharmaceutics
• 出版年：2014
• 出版时间：September 2, 2014
• 年：2014
• 卷：11
• 期：9
• 页码：3017-3026
• 全文大小：504K
• ISSN：1543-8392

文摘

A mitomycin C (MMC)鈥搒oybean phosphatidyhlcholine complex loaded in phytosomes was previously reported for the purpose of developing a MMC drug delivery system (Mol. Pharmaceutics 2013, 10, 90鈥?01), but this approach was limited by rapid elimination from the body and lack of target specificity. In this article, to overcome these limitations, MMC鈥搒oybean phosphatidyhlcholine complex-loaded phytosomes (MMC-loaded phytosomes) as drug carriers were surface-functionalized with folate-PEG (FA-PEG) to achieve reduced toxicity and a superior MMC-mediated therapeutic effect. For this purpose, FA was conjugated to DSPE-PEG-NH₂, and the resultant DSPE-PEG-FA was introduced into the lipid moiety of the phytosomes via a postinsertion technique. The prepared FA-PEG-functionalized MMC-loaded phytosomes (FA-PEG-MMC-loaded phytosomes) have a particle size of 201.9 卤 2.4 nm, a PDI of 0.143 卤 0.010, a zeta potential of 鈭?7.50 卤 1.67 mV, a spherical shape, and sustained drug release. The remarkable features of FA-PEG-MMC-loaded phytosomes included increased cellular uptake in HeLa cells and higher accumulation in H₂₂ tumor-bearing mice over that of the PEG-MMC-loaded phytosomes. Furthermore, FA-PEG-MMC-loaded phytosomes were associated with enhanced cytotoxic activity in vitro and an improved antitumor effect in vivo compared to that resulting from free MMC injection. These results suggest that FA-PEG-MMC-loaded phytosomes may be useful drug delivery systems for widening the therapeutic window of MMC in clinical trials.

Keywords:

mitomycin C; drug delivery; tumor targeting; cancer therapy; phytosomes