Core-matched encapsulation of an oleate prodrug into nanostructured lipid carriers with high drug loading capability to facilitate the oral delivery of docetaxel.

Autor: Sun B; School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China., Luo C; School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China., Li L; School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China., Wang M; School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China., Du Y; School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China., Di D; School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China., Zhang D; School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China., Ren G; School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China., Pan X; Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23220, USA., Fu Q; School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China., Sun J; School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China; Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Electronic address: sunjin66@21cn.com., He Z; School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Electronic address: hezhonggui@vip.163.com.
Jazyk: angličtina
Zdroj: Colloids and surfaces. B, Biointerfaces [Colloids Surf B Biointerfaces] 2016 Jul 01; Vol. 143, pp. 47-55. Date of Electronic Publication: 2016 Mar 02.
DOI: 10.1016/j.colsurfb.2016.02.065
Abstrakt: Nanostructured lipid carriers (NLC) have been considered as promising vehicles for oral delivery of taxanes, such as docetaxel (DTX). However, the low drug loading capability (∼5%, w/w) has greatly limited their clinical application. In response to this challenge, a novel lipophilic oleate prodrug of DTX (DTX-OA) was synthesized and efficiently encapsulated in NLC using core-match technology, in which liquid lipid (OA) was used as core matrix to enhance compatibility with DTX-OA. DTX-OA-NLC showed uniform particle size of about 100nm with markedly high drug loading capability (∼23% of DTX, w/w) compared with DTX-NLC (∼5%, w/w). Besides, DTX-OA-NLC showed better colloidal stability and slower drug release property compared with DTX-NLC. The prepared NLC could be accumulated more easily in MDCK cells than drug solution, and clathrin-mediated endocytosis was the main endocytosis pathway. In situ single-pass intestinal perfusion (SPIP) and intestinal biodistribution studies demonstrated the improved membrane permeability and intestinal wall bioadhesion of NLCs. The bioavailability of DTX-OA-NLC showed 4.04-fold and 2.06-fold higher than DTX solution and DTX-NLC, respectively. These results suggest that the core-matched prodrug-NLC is a promising platform to facilitate the oral delivery of DTX.
(Copyright © 2016. Published by Elsevier B.V.)
Databáze: MEDLINE
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