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

J Drug Target. 2005 Jan;13(1):73-80. doi: 10.1080/10611860400011935.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

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