Biodegradable polymersomes as carriers and release systems for paclitaxel using Oregon Green® 488 labeled paclitaxel...

Oregon Green® 488 labeled paclitaxel (Flutax) loaded biodegradable polymersomes (Flutax-Ps) based on methoxy poly(ethylene glycol)-b-poly(d,l-lactide) (mPEG-PDLLA), methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) or a mixture of the block copolymers (50:50, w/w) were prepared (abbreviated as Flutax-Ps (L), Flutax-Ps (C) and Flutax-Ps (LC), respectively). For the formation of the Ps, the corresponding block copolymers and Flutax were dissolved in THF and the THF solution was injected into an aqueous phase. Flutax-Ps with a size less than 150nm were obtained, which had Flutax entrapment efficiencies higher than 55% (polymer concentration: 1mg/ml; Flutax concentration up to 100μg/ml). A sustained and complete release of Flutax was observed for Flutax-Ps (L) over one month with no initial burst. Flutax was released much slower from Ps (C) than from Ps (L) (49.9% after one month), which is probably due to differences in the crystallinity and rate of degradation of the consisting copolymers. The release rate of Flutax from Ps (LC) was in between those of Ps (L) and Ps (C). The in vitro cytotoxicity of Flutax-Ps (L) using cultured SKBR3 breast cancer cells was compared with that of empty Ps (L) and a Cremophor® EL/ethanol formulation (50:50, v/v) with Flutax (FCE) or without Flutax (CE). At a Flutax concentration of 5μg/ml, about 67% reduction in the viability of SKBR3 cells was observed for Flutax-Ps (L) after 3days exposure, while the FCE formulation reduced the cell viability for more than 90% under the same conditions. Empty Ps (L) showed a low toxicity of about 10% and the CE formulation exhibited a cytotoxicity higher than 54% without Flutax, indicating that the high reduction in SKBR3 cell viability for FCE is associated with the toxicity of the Cremophor® EL formulation.