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Preparation and evaluation of paclitaxel-loaded PEGylated immunoliposome



Preparation and evaluation of paclitaxel-loaded PEGylated immunoliposome



Journal of Controlled Release 120(3): 169-177



A sterically stabilized paclitaxel-loaded liposome tailored to target human breast cancer cells was developed, thereby promoting the efficiency of intracellular delivery of paclitaxel through receptor-mediated endocytosis. Results indicated that the targeting moiety (thiolated Herceptin) was successfully coupled to the distal reactive maleimide terminus of the poly (ethylene glycol)-phospholipid conjugate as well as being incorporated in the liposomal bilayers. The particle size of the PEGylated immunoliposome was maintained at about 200 nm. Confocal microscopy studies showed that the PEGylated immunoliposome was uptaken into the interior of the tumor cell through the receptor-mediated endocytosis pathway. The PEGylated immunoliposome showed substantially higher cellular uptake than the PEGylated liposome in cancer cells (BT-474 and SK-BR-3) over-expressing human epidermal growth factor receptor 2 (HER2) at 37 degrees C, while no difference was found in low HER2 expressing cells (MDA-MB-231) nor at low temperature (4 degrees C). Pharmacokinetics of paclitaxel in the PEGylated immunoliposome was compared with that in Taxol and in the PEGylated liposome in rats. The circulating time of paclitaxel in the PEGylated immunoliposome was prolonged compared to Taxol while slightly shortened than that in the PEGylated liposome. Therefore, the paclitaxel-loaded PEGylated immunoliposome using Herceptin could serve as a promising model for future tumor specific cancer therapy of HER2 over-expressing breast cancers.

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Accession: 016733038

Download citation: RISBibTeXText

PMID: 17586082

DOI: 10.1016/j.jconrel.2007.05.011


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