Desenvolvimento e caracterização de micropartículas poliméricas contendo curcumina e piperina com potencial antioxidante em dislipidemias

Abstract

The use of phytopharmaceuticals for preventing and treating dyslipidemias shows remarkable interest in the pharmaceutical industry by reducing atherosclerosis events and other cardiovascular diseases. Curcumin (CUR) is a phenolic compound extracted from the rhizomes of Curcuma longa L. and shows high pharmacological potential by interacting with several molecular targets. Among its pharmacological activities, CUR presents strong evidence in the reduction of serum lipids and hepatoprotective action. However, it has photosensitivity and low bioavailability. Piperine (PIP) is an alkaloid found in fruits and roots of the species Piper nigrum L. and Piper longum L. This secondary metabolite has some pharmacological properties as reduction of fat, obesity, and blood lipid levels. It has a high degree of pungency, low water solubility and a promising effect to increase the bioavailability of other drugs. Considering the physicochemical limitations of CUR and PIP and the aim of increasing their bioavailability for use them in future lipid-lowering and hepatoprotective pharmaceutical formulations, the objective of this work was to develop, to characterize and to evaluate in vitro polymeric microparticles using Eudragit® S100 and RS30D by spray-drying technique. The formulations were prepared in ethanol:water (50:50, V/V) containing 0, 10 and 20% of pure drugs alone and/or in combination. Microparticles with suitable size (1.86 to 7.75 μm), yield (12.41 to 69.33%), and moisture (2.54 to 4.93%) were achieved. The drug was quantified using an analytical method by high performance liquid chromatography (HPLC). This method was specific, linear, precise, and exact. The Eudragit® S100 microparticles were spherical or semi-spherical in shape, presented smooth surface and some irregularities. The encapsulation efficiency was between 81.42 and 109.75%. For Eudragit® RS30D, erythrocyte-like structures and encapsulation efficiency between 84.65 and 102.5% were obtained. No free drug was found on the surface of any microparticle formulation. Fourier transform infrared spectroscopy (FTIR) did not show chemical bonds between drugs and polymers. The results obtained by X-ray diffraction (XRD) and thermal analysis (TGA) indicated drug amorphization comparing to pure CUR and PIP. In vitro tests showed no hemolytic effect and with antioxidant effect associated with lipid metabolism. Considering the results obtained, (meth)acrylic microparticle formulations containing CUR and PIP may be a feasible alternative for further in vivo assays in atherosclerosis model.