Polymeric micelles for delivery of poorly soluble drugs: preparation and anticancer activity in vitro of paclitaxel incorporated into mixed micelles based on poly(ethylene glycol)-lipid conjugate and positively charged lipids.

Abstract

Paclitaxel-loaded mixed polymeric micelles consisting of poly(ethylene glycol)-distearoyl phosphoethanolamine conjugates (PEG-PE), solid triglycerides (ST), and cationic Lipofectin lipids (LL) have been prepared. Micelles with the optimized composition (PEG-PE/ST/LL/paclitaxel = 12/12/2/1 by weight) had an average micelle size of about 100 nm, and zeta-potential of about -6 mV. Micelles were stable and did not release paclitaxel when stored at 4 degree C in the darkness (just 2.9% of paclitaxel have been lost after 4 months with the particle size remaining unchanged). The release of paclitaxel from such micelles at room temperature was also insignificant. However, at 37 degree C, approx. 16% of paclitaxel was released from PEG-PE/ST/LL/paclitaxel micelles in 72 h, probably, because of phase transition in the ST-containing micelle core. In vitro anticancer effects of PEG-PE/ST/LL/paclitaxel and control micelles were evaluated using human mammary adenocarcinoma (BT-20) and human ovarian carcinoma (A2780) cell lines. Paclitaxel in PEG-PE/ST/LL micelles demonstrated the maximum anti-cancer activity. Cellular uptake of fluorescently-labeled paclitaxel-containing micelles by BT-20 cells was investigated using a fluorescence microscopy. It seems that PEG-PE/ST/LL micelles, unlike micelles without the LL component, could escape from endosomes and enter the cytoplasm of BT-20 cancer cells thus increasing the anticancer efficiency of the micellar paclitaxel.

• Authors: Junping Wang, Dimitry Mongayt, Vladimir P Torchilin
• Journal: Journal of drug targeting (J Drug Target) Vol. 13 Issue 1 Pg. 73-80 (Jan 2005) ISSN: 1061-186X [Print] England
• PMID: 15848957 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Lipids
• Micelles
• Triglycerides
• Polyethylene Glycols
• Paclitaxel

Topics

• Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
• Chemistry, Pharmaceutical (methods)
• Drug Carriers (chemistry, metabolism, pharmacology)
• Drug Screening Assays, Antitumor (methods)
• Electrochemistry (methods)
• Humans
• Lipids (chemistry, pharmacology)
• Micelles
• Microscopy, Fluorescence (methods)
• Paclitaxel (pharmacology)
• Polyethylene Glycols (chemistry, metabolism, pharmacology)
• Solubility
• Triglycerides (pharmacology)
• Tumor Cells, Cultured