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Preparation, characterizations, and in vitro metabolic processes of paclitaxel-loaded discoidal recombinant high-density lipoproteins.

Discoidal recombinant high-density lipoproteins (d-rHDLs) are attractive candidates for anticancer agents because of their favorable biocompatibility, biodegradability, and receptor-mediated endocytosis. Paclitaxel (PTX)-loaded d-rHDLs (P-d-rHDLs) were prepared by thin-film dispersion/detergent dialysis methods in this study. To investigate metabolic processes that P-d-rHDLs probably encounter in circulation, influences of lecithin-cholesterol acyltransferase (LCAT) on structural and compositional changes of P-d-rHDLs were studied in vitro. The shape of P-d-rHDLs converted from discoid into sphere, particle size increased, and cholesteryl ester (CE) generated simultaneously, which were referred to as remodeling behaviors. In vitro releases tests showed that release rate of PTX from P-d-rHDLs became faster when LCAT was added to P-d-rHDLs suspensions. Human breast cancer cells' cytotoxicity and cellular uptake of P-d-rHDLs were higher than liposomes and Taxol, and decreased in the presence of LCAT. Explorations of above phenomena found that drug entrapment did not influence remodeling processes induced by LCAT, whereas there was drug leakage occurring in remodeling processes. Therefore, drug leakage resulting from remodeling processes under the action of LCAT should be paid more attentions to when using d-rHDLs as drug vehicles for anticancer drugs. This study first focuses on metabolic processes of drug carriers and elucidates them through in vitro tests.