Desenvolvimento de nanopartículas híbridas para administração de paclitaxel por via intranasal.

Abstract

Malignant tumors of the central nervous system represent one of the main causes of cancer-related mortality, with glioblastoma multiforme standing out as a primary concern. The standard treatment, which includes surgical resection, radiotherapy, and chemotherapy with temozolomide, provides limited benefits due to the high recurrence rate and significant side effects. Paclitaxel emerges as a promising alternative; however, the blood-brain barrier hinders its application, and the use of nanoparticles has been investigated to overcome these limitations. This study aimed to prepare a hybrid nanoparticle loaded with paclitaxel and incorporate it into a thermosensitive hydrogel with suitable characteristics for nose-to-brain administration. To determine the optimized production conditions for the nanoparticle, different proportions of lipids and polymers, as well as surfactant concentrations, were tested. The nanoparticle was developed using the nanoprecipitation method followed by solvent evaporation. The results showed an average diameter of less than 200 nm, a straight particle size distribution, a zeta potential close to -30.0 mV, and a pH of around 6.0. The average encapsulation efficiency for the most promising formulation was 60%. Additionally, thermosensitive hydrogel formulations composed of different polymers and concentrations were evaluated using the cold solubilization method. After incorporating the nanoparticles, the gelation temperature was 35.6°C, with a rapid gelation time (35–41 seconds) at 37°C and (130 148 seconds) at 34°C, within the temperature range of the human nasal cavity. The formulations demonstrated a suitable spray profile for intranasal administration. The droplet size distribution profiles of the formulations resulted in a Dv50 value compatible with nasal spray products. The mucopenetration capacity of the formulations was demonstrated through interaction studies with mucin, a protein present in nasal cavity mucus. The developed formulations exhibited superior antiglioma activity compared to temozolomide when evaluated in the U87 tumor cell line. The results of this study are promising, suggesting that the developed formulation has the potential to deliver PTX for nose-to-brain applications targeting the treatment of brain tumors.