Síntese de nanopartículas híbridas como sistema vetorizado para entrega tópica de compostos ativos : experimentos e modelagem matemática

Abstract

Human skin is an attractive option for applying active compounds that minimize adverse effects due to low systemic exposure when compared with other routes of administration. These compounds can permeate the skin layer by the intercellular, intracellular and follicular routes resulting in a topical and/or transdermal delivery. The delivery of active compounds via nanotechnology-based systems may revolutionize the treatment of several disorders including the ones related with the skin. Among these systems, liposomes, and biocompatible and bioabsorbable polymeric nanoparticles, are the technologies with the greatest growth in the field. Therefore, it is ideal to look for mechanisms that couple the mechanical advantages of polymeric nanoparticles with the biomimetic characteristics of liposomes. The aim of this work is to study the synthesis and behavior of hybrid nanoparticles comprising a polymeric core (PLGA) coated by a mixture of lipids (HSPC:CHOL:DSPE-PEG) functionalized to ligand molecules. Initially, it is proposed the conjugation of vitamin D on the surface of the hybrid nanoparticles to target them for specific receptors (VDR) present on melanocytes and melanoma cells. Subsequently, the synthesis of a RGD peptide is carried out aiming to verify the possibility of applying the same methodology for targeting more specific receptors of these cells. Seeking a greater understanding about how the drug is released from these nanoparticles, in vitro experiments of drug release are conducted. In addition, an explicit analytical solution of the mathematical model proposed by Baker-Lonsdale is proposed in order to obtain information regarding the transport phenomena that controls the drug release. Finally, it is proposed a skin permeation mathematical model with boundary conditions adapted for the target nanoparticles.