Cancer 2013 May (2)-14

 

2-Hydroxypropyl-β-cyclodextrin-modified SLN of paclitaxel for overcoming p-glycoprotein function in multidrug-resistant breast cancer cells.

J Pharm Pharmacol. 2013 Jan;65(1):72-8

Baek JS, Cho CW.

College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Yuseong-gu, Daejeon, South Korea.

Abstract

OBJECTIVES: This study aimed to evaluate the potential of solid lipid nanoparticles (SLNs) of paclitaxel (PTX) modified with a 2-hydroxypropyl-β-cyclodextrin system to enhance cellular accumulation of PTX into p-glycoprotein (p-gp)-expressing cells.

METHODS: The PTX-loaded-SLNs consisted of lipid (stearic acid) and surfactants (lecithin and poloxamer 188) and were then modified with 2-hydroxypropyl-β-cyclodextrin by a sonication method.

KEY FINDINGS:

In terms of cytotoxicity, PTX-loaded SLNs modified with 2-hydroxypropyl-β-cyclodextrin showed higher cytotoxicity than other formulations. In particular, the cellular uptake of PTX from PTX-loaded SLNs modified with 2-hydroxypropyl-β-cyclodextrin was about 5.8- and 1.5-fold higher than that from PTX solution and unmodified PTX-loaded SLNs in MCF-7/ADR cells, respectively. After a 4-h incubation, clear fluorescence images inside cells were observed over time. When PTX-loaded SLNs modified with 2-hydroxypropyl-β-cyclodextrin were incubated with MCF-7/ADR cells for 4 h, cellular uptake of PTX increased 1.7-fold versus that of PTX in the presence of verapamil.

CONCLUSIONS: These results suggest that optimized SLNs modified with 2-hydroxypropyl-β-cyclodextrin may have potential as an oral drug delivery system for PTX. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

PMID: 23215690

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