Desenvolvimento e caracterização físico-química de lipossomas contendo cabazitaxel

Abstract

Cabazitaxel is a clinically approved drug for the treatment of metastatic castration-resistant prostate cancer. However, the drug molecule is lipophilic and has unfavorable pharmacokinetics, limiting clinical success. Thus, pharmaceutical nanotechnology emerges as a viable alternative to circumvent the limitations of treatment with cabazitaxel, allowing increased stability, sustained drug release, improved pharmacokinetics and passive increase in tumor uptake, resulting in improved therapeutic efficacy with reduced Side effects. In the present work, the objective is the development and physicochemical characterization of liposomes with long circulation time containing cabazitaxel. For this purpose, a qualitative by design development strategy was used, with a box-benhken factorial planning tool, with the determination of relevant independent variables for the encapsulation of cabazitaxel, such as type of lipid, drug/lipid ratio and percentage molar concentration, adopting as dependent variables particle size, polydispersity index, evaluated by dynamic light scattering and encapsulation efficiency, quantified by UV-spectrophotometry. The nanoparticles produced by hydration of the lipid film had a particle size of 136 ± 2.21 nm, polydispersity index 0.335 ± 0.006, zeta potential -10.9 ± 0.49 mV and encapsulation efficiency of 93.78 ± 0.51 %. The physicochemical characterizations of DSC and FTIR allowed to conclude that cabazitaxel is in the amorphous state or molecularly dispersed in the liposomal matrix and the atomic force microscopy indicated the morphology of the liposomes as lipid vesicles without roughness. Finally, the dissolution study showed the slow and sustained release of the drug, the release profile found was compared to different kinetic models of release, and the Weibull model was considered more adequate. In conclusion, the developed system has appropriate physicochemical characteristics for the delivery of cabazitaxel, whose potential application in the treatment of prostate cancer will be evaluated in in vitro and in vivo studies.