Desenvolvimento, caracterização e estabilidade de carreadores lipídicos nanoestruturados de Cumarina visando o desenvolvimento de nanofármaco

Abstract

The coumarin (C) is a compound present in many medicinal plants typical of the northeastern region and has many proven pharmacological activities such as anti-inflammatory and antinociceptive. However, it has ready absorption and fast metabolism, characteristics that can hamper the development of pharmaceutical formulations from this molecule. Thus, encapsulation of C and use of formulations with controlled release can provide an alternative to overcome the problems in using it. Given that, the objective of this study was to develop, characterize and monitor the stability of a nanostructured lipid carrier C (CLNC). To this end, two formulations were made with different concentrations of lipid phase (5% to 10%) by high pressure homogenization in hot-technique using Precirol ATO5® and Miglyol 812® as the matrix forming lipids. The CLNC was characterized by the diameter (D), polydispersity index (PDI), the zeta potential (PZ), pH, content and encapsulation efficiency (EE). The suspensions obtained had samples collected at different homogenization cycles (1, 3 and 5 cycles), to be evaluated the influence of the number of cycles in the stability, accompanied by a period of 90 days. Right after the production, all samples showed homogeneous appearance and no signs of instability, however, from the 15th day, samples submitted for only one cycle (1C) and the one with the highest percentage of lipid phase and three cycles had precipitated. Although other formulations also remain stable, the CLNC-10% 5C was selected to continue with the characterization because of its higher concentrations of C and showed initial D of 176.9 ± 2.0 nm with an increase to 189.1 ± 2, 6. PDI remained in narrow distribution range (less than 0.2), the slightly acidic pH remained stable (around 4.77), the initial content 95.5% experienced a small decrease with storage time, achieving 85,8%, and EE was constant during the study days (approximately 65%). Given the above mentioned it was observed that the formulations were stable when employed a larger number of homogenization cycles, with low loss of C and constant EE. The CLNC-105C presented technological characteristics of interest and stability, being a product with potential for development of a nanomedicine with favorable pharmacokinetic characteristics for therapeutic use.