Open Access2‐Hydroxypropyl‐ β ‐cyclodextrin‐modified SLN of paclitaxel for overcoming p‐glycoprotein function in multidrug‐resistant breast cancer cells
Author(s) -
Baek JongSuep,
Cho CheongWeon
Publication year - 2013
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/j.2042-7158.2012.01578.x
Subject(s) - paclitaxel , chemistry , cytotoxicity , sonication , poloxamer , solid lipid nanoparticle , cyclodextrin , p glycoprotein , hydroxypropyl cellulose , pharmacology , drug delivery , multiple drug resistance , chromatography , biochemistry , chemotherapy , in vitro , medicine , organic chemistry , surgery , antibiotics , copolymer , polymer
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.