Nanohíbridos termoresponsivos contendo poloxaminas e Laponita como carreadores de Beta-Lapachona: plataforma para terapia anticâncer

Abstract

Tetronics® are copolymers that form micelles and have the ability to reversibly transition between the sol-gel phases according to their concentration, pH and temperature, and can be used in controlled release systems for drugs of low aqueous solubility. Tetronics® T904, T90R4 and T1304 were used for β-lapachone incorporation (BLPC), which was selected for its several biological activities, characterized in particular as anticancer and anti-inflammatory properties and by presenting a very low aqueous solubility (0.038 mg.ml -1 ), which limits its bioavailability and systemic administration. The synthetic hectorite Laponite RD® (LAP), which forms hydrogels, was added as a rheological modifier to aid in the physical-chemical stability of the micelles. The samples were prepared by varying from 1 to 20% the polymer concentrations and from 0 to 3%, that of Laponite. The parameters analyzed were: the increase in BLPC solubility, rheological behavior of the systems, particle size by dynamic light scattering, characterization by thermal analysis (TG and DSC) and infrared spectrometry, release profile and in vitro cytotoxicity in murine fibroblasts and human adenocarcinoma cells. Hybrid systems exhibited thermal stability and increased the solubility of BLPC more than 50 times with respect to water. There was evince of BLPC encapsulation in the micellar systems which promoted a controlled release of BLPC for 140 hours and were more efficient in killing cancer cells in in vitro assays than the free drug.