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

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

Junping Wang  1 , Dimitry Mongayt, Vladimir P Torchilin
Affiliations

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

Junping Wang et al. J Drug Target. 2005 Jan.

Erratum in

  • J Drug Target. 2005 Jan;13(1):71

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.

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Figures

Figure 1
Figure 1
The effect of the ST content in mixed micelles on paclitaxel micellization efficiency.
Figure 2
Figure 2
The in vitro release of paclitaxel from mixed PEG-PE/ST/LL/paclitaxel (12/12/2/1 by weight) micelles in PBS, pH =7.4 at different temperatures.
Figure 3
Figure 3
The in vitro viability of A2780 cancer cells after the incubation with different paclitaxel preparations. See “Materials and methods section” for details.
Figure 4
Figure 4
The in vitro viability of BT-20 cancer cells after the incubation with different paclitaxel preparations. See “Materials and methods section” for details.
Figure 5
Figure 5
Light (left images in each pair) and fluorescent (right images in each pair) microscopy of BT-20 cells incubated with Rh-PE-labeled PEG-PE/ST/paclitaxel micelles and PEG-PE/ST/LL/paclitaxel micelles for 0.5, 2, and 4 h. Arrows on fluorescent microscopy images show: fluorescent endosomes in cells incubated with PEG-PEG-PE/ST/LL/paclitaxel micelles for 0.5 h and with PEG-PE/ST/paclitaxel micelles for 2 h; partially degraded endosomes in cells incubated with PEG-PE/ST/LL/paclitaxel micelles for 2 h; fused late endosomes in cells incubated with PEG-PE/ST/paclitaxel micelles for 4 h; small fluorescent structures in cells incubated with PEG-PE/ST/LL/paclitaxel micelles for 4 h. See “Materials and methods section” for details.
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