"Desenvolvimento de nanopartículas lipídicas sólidas contendo ácido retinóico e ácido láurico para o tratamento tópico da acne vulgaris"

Abstract

Topical therapy is the first choice in the treatment of mild to moderate acne and all-trans retinoic acid (tretinoin, RA) is one of the most used drugs. However, its topical application is followed by high incidence of side-effects, including erythema and irritation. Solid lipid nanoparticles (SLN) are an interesting alternative to reduce side-effects without compromising efficacy. On the other hand, combination of retinoids and antimicrobials represents an innovative approach in topical therapy of acne, and, recently, lauric acid (LA), a fatty acid present in sebum, has shown strong activity against Propionibacterium acnes. This work aims to develop SLN loaded with RA and LA. The influence of stearylamine (SA), a lipophilic amine, over the characteristics of SLN was investigated. SLN were prepared by the hot melt homogenization method using an emulsification-ultrasound. The mean particle diameter was similar for the three levels of SA evaluated (0, 0.2 and 0.4%) and zeta potential increased according to the level of SA. Encapsulation Eficiency (EE) of the acids was evaluated 0 and 15 days after preparation. EE of RA and LA was high at initial time for the three levels of SA. However, a significant decrease for EE of RA was observed 15 days later in SLN with 0% of SA. SLN loaded with RA and LA were characterized by Differential Scanning Calorimetry (DSC) and X-ray Diffraction (XRD). The DSC thermograms and XRD diffractograms showed integration of RA and LA to the lipid matrix of SLN, suggesting that LA was able to disrupt the lipid matrix, allowing the increased EE of RA. The in vitro growth inhibitory activity was evaluated for Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis. SLN loaded with RA and LA inhibited the growth of the evaluated microorganisms, with important role of the positive charge of SA. In summary, it was demonstrated that SLN loaded with LA facilitate the incorporation of RA and the presence of SA is important to ensure good stability of encapsulation. Moreover, SLN loaded with RA and LA show potential antimicrobial activity, representing an interesting alternative for topical treatment of acne vulgaris. Keywords: Acne vulgaris, topical therapy, solid lipid nanoparticles, retinoic acid, lauric acid.