1. Mixed PEG-PE/Vitamin E Tumor-Targeted Immunomicelles as Carriers for Poorly Soluble Anti-Cancer Drugs: Improved Drug Solubilization and Enhanced In Vitro Cytotoxicity
- Author
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Rishikesh M. Sawant, Rupa R. Sawant, and Vladimir P. Torchilin
- Subjects
Drug ,Time Factors ,Paclitaxel ,Cell Survival ,media_common.quotation_subject ,Chemistry, Pharmaceutical ,Pharmaceutical Science ,Micelle ,Article ,Polyethylene Glycols ,chemistry.chemical_compound ,Mice ,Drug Stability ,Cell Line, Tumor ,PEG ratio ,medicine ,Animals ,Technology, Pharmaceutical ,Vitamin E ,Particle Size ,Cytotoxicity ,Micelles ,media_common ,Drug Carriers ,Dose-Response Relationship, Drug ,Hydrolysis ,Phosphatidylethanolamines ,Antibodies, Monoclonal ,General Medicine ,Antineoplastic Agents, Phytogenic ,In vitro ,Nucleosomes ,Biochemistry ,chemistry ,Solubility ,Camptothecin ,Drug carrier ,Biotechnology ,medicine.drug - Abstract
Two poorly soluble, potent anticancer drugs, paclitaxel and camptothecin, were successfully solubilized by mixed micelles of polyethylene glycol-phosphatidyl ethanolamine (PEG-PE) and vitamin E. Drug containing micelles were additionally modified with anti-nucleosome monoclonal antibody 2C5 (mAb 2C5), which can specifically bring micelles to tumor cells in vitro. The optimized micelles had an average size of about 13-to-22 nm and the immuno-modification of micelles did not significantly change it. The solubilization of both drugs by the mixed micelles was more efficient than by micelles made of PEG-PE alone. Solubilization of camptothecin in micelles prevented also the hydrolysis of active lactone form of the drug to inactive carboxylate form. Drug loaded mixed micelles and mAb 2C5-immunomicelles demonstrated significantly higher in vitro cytotoxicity than free drug against various cancer cell lines.
- Published
- 2008