title: Therapeutic effect of folate-targeted and PEGylated phytosomes loaded with a mitomycin C-soybean phosphatidyhlcholine complex.
abstract: A mitomycin C (MMC)-soybean phosphatidyhlcholine complex loaded in phytosomes was previously reported for the purpose of developing a MMC drug delivery system (Mol. Pharmaceutics 2013, 10, 90-101), but this approach was limited by rapid elimination from the body and lack of target specificity. In this article, to overcome these limitations, MMC-soybean 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 ± 2.4 nm, a PDI of 0.143 ± 0.010, a zeta potential of -27.50 ± 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.
authors: Department of Biomaterials & Materials Science and Engineering, College of Materials, ‡Department of Pharmacy, School of Pharmaceutical Sciences, and §Department of Chemistry, College of Chemistry & Chemical Engineering, Xiamen University , Xiamen 361005, China.
authors: Yang
authors: Y
authors: Li
authors: Hongjie
authors: H
authors: Wu
authors: Mengmeng
authors: M
authors: Jia
authors: Fei
authors: F
authors: Cui
authors: Jinyan
authors: J
authors: Lin
authors: Xiangrui
authors: X
authors: Yang
authors: Yange
authors: Y
authors: Wang
authors: Lingfeng
authors: L
authors: Dai
authors: Zhenqing
authors: Z
authors: Hou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005492:Folic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013025:Glycine max / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011108:Polymers; C552831:poly(ethylene glycol)-folate; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D016685:Mitomycin; D005492:Folic Acid