Encapsulamento de rivastigmina em nanopartículas de P(MMA-co-AA) funcionalizadas para tratamento de doenças neurodegenerativas

Abstract

The Alzheimer disease is a terminal illness that is associated mostly with aging. For this reason a significant growth of the number of patients is expected to take place in the forthcoming decades. The medications currently used exert adverse effects and great difficulty to cross the blood-brain barrier, where the target is located. Rivastigmine is widely used in early and moderate phases of the disease. For this reason, the present work proposes the encapsulation of this drug in functionalized P(MMA-co-AA) nanoparticles for site-specific delivery. The comonomer content was varied between 7.5wt% and 15wt% in the reaction medium, leading to incorporation of 3 to 5% in copolymer. Despite the high encapsulation efficiencies (above 70wt%), 0.5wt% of the drug was suffient to provoke interaction between the reaction media and the drug. The best conformation attained was 205.63 mg encapsulated in P(MMA-co-AA) 7.5wt%. Bio conjugation technique were used satisfactorily to functionalize polymer particles and both the copolymer composition and drug content did not affect the process. The cytotoxic concentration obtained was shown to be similar for all tested formulations and lower than clinical trial concentrations (1400 μg nanoparticle / mL and 50 μg rivastigmine / mL). High permeability through cell membrane was obtained in all cases, even when bioconjugation with TAT was not performed. Thus, it is possible to assume the potential use of these nanoparticles as carriers of rivastigmine through physiological barriers.