Obtenção de micelas poliméricas mistas carreadoras de paclitaxel.

Abstract

Our research group developed previously distearoylphosphatidylethanolamine- polyethyleneglycol (DSPE-PEG2000) polymeric micelles carrying PTX which showed promising physicochemical and biological characteristics for aplication in cancer treatment. Aiming to continuing studying these systems, the development of mixed polymeric micelles emerged as an interesting approach to possibly improve some of its properties and overcome limitations observed for the conventional micelle formulation. The objective of this study was to obtain and characterize, under the physicochemical aspect, mixed micelle formulations containing DSPE-PEG2000 and poly-Ɛ-caprolactone-polyethylene glycol (PCL5000-PEG5000) in molar ratios of 99.5:0.5 and 99:1, respectively, with appropiate characteristics for carrying PTX. The mixed micelles exhibited a mean diameter of 10,7 ± 1,4 nm and a zeta potential of -4,2 ± 1,7 mV, the highest loading efficiencies were obtained for formulations containing 1.0 mg/mL of PTX (> 82%). The results obtained by SAXS suggested that variations in the copolymer molar ratio and PTX concentration impacted structural organization parameters such as aggregation number, density of PEG chains and sizes of core and shell radius. These alterations indicated improvement in the mixed micelle loading capacity (maximum 1 mg/mL of PTX) when compared with the DSPE-PEG2000 formulation (maximum 0.6 mg/mL of PTX). Thermal analysis techniques allowed to study the effect of the PCL5000-PEG5000 presence in the mixed micellar system, a decrease in melting enthalpy value and a impact on decomposition phenomena was observed. Compared to the conventional micelle formulation, an increase in the amount of drug retained after seven days was observed in an aqueous environment, however, it was found that the copolymer insertion did not represent an important effect of stability improvement over 60 days. The in vitro release study showed a sustained profile with a release of about 60% PTX in 48 hours in a aqueous medium containing sodium salicylate. It was not possible to observe difference in the release profile of the mixed micelle formulation containing 0.5% PCL5000-PEG5000 when compared to the DSPE-PEG2000 formulation, in addition, the formulation similar to Taxol® presented the slower release profile. Finally, these findings suggested that the mixed polymeric micelle system is a promising PTX carrier, which showed improved physicochemical characteristics when compared to the conventional micellar system.