Desenvolvimento e caracterização de nanocápsulas poliméricas contendo isradipino com potencial efeito neuroprotetor

Abstract

Isradipine, a calcium channel blocker which belongs to the class of dihydropyridines, presents a neuroprotective mechanism associated with an inhibition of the progression of neurodegenerative diseases. The main challenge is to become this drug able to cross the blood-brain barrier in therapeutic concentrations. In this way, polymeric nanocapsules show an interesting application for providing drugs in the central nervous system, followed by the controlled release of these drugs at this site. In this sense, this work aims to develop and characterize nanocapsules containing isradipine, using the blend of poly(ε-caprolactone) (PCL), 10000 g.mol-1, and polyethylene glycol (PEG), 6000 g.mol-1, and polysorbate 80 coating, in order to improve the availability of this drug in the central nervous system. The polymeric nanocapsules containing isradipine were successfully prepared by the interfacial deposition of the preformed polymer procedure and were subsequently coated with polysorbate 80. The formulation was characterized by morphological and surface analyzes, particle size and zeta potential, as well as spectroscopic and thermal analyzes. In order to measure the amount of drug encapsulated, an analytical method was developed and validated employing an ultra-high performance liquid chromatography followed by an ultraviolet wavelength detection. The nanoparticulate systems presented a spherical shape with a smooth and regular surface and average particle size of 251.3 nm, polydispertion index of 0.239 and zeta potential of -36.7 mV. The X-ray diffraction pattern confirmed that the encapsulation method was efficient and the drug primarily is in molecular dispersion in the oily nucleus of the nanocapsules. The Fourier transform infrared spectrum ensured that the nanoencapsulation process did not result in chemical bonds between the isradipine and the polymers. Thermal analysis demonstrated that the formulation is stable up to 86 °C. The formulation presented an encapsulation efficiency greater than 98% and the analytical method employed proved to be selective, linear for the suggested range, precise, accurate and robust, and capable of quantifying nanoencapsulated isradipine in polymeric systems, providing reliable results. Therefore, the results provide an experimental basis in order to make feasible the use the blend of PCL-PEG nanocapsules containing isradipine, coated with polysorbate 80, as an alternative for drug releasing in the central nervous system.