Desenvolvimento tecnológico de nanopartículas poliméricas contendo colecalciferol

Abstract

Vitamin D is a lipid-soluble compound of plant origin (vitamin D2 or ergocalciferol) or animal (vitamin D3 or cholecalciferol), responsible for calcium homeostasis, in addition to a pleiotropic effect. The major source of cholecalciferol for humans is the skin exposure to solar radiation. Vitamin D deficiency is considered a global health problem being that, hypovitaminosis D can be corrected by skin exposure to sunlight, food or oral administration of cholecalciferol. Currently the skin exposure to sunlight is limited and the amount ingested through the diet is not enough and oral replacement may present flaws, due to poor adherence of the patient to the treatment. Thus, in order to elaborate modified release systems, and to protect the drug due it’s lability, resulting in a more stable formulation, the objective of this work was to obtain and characterize suspensions of polymeric nanoparticles, for administration by the transdermal route of the cholecalciferol. Therefore, the formulations were obtained and performed the physical-chemical characterization through: medium size, zeta potential, polydispersity index, pH, suspension stability, vitamin D encapsulation efficiency, field scanning electron microscopy, diffraction X-ray spectroscopy, differential scanning calorimetry, thermogravimetric analysis and in vitro study of skin permeation study. An analytical method was developed and validated by high-performance liquid chromatographfor quantification of the drug. Polymeric nanoparticles were prepared by the nanoprecipitation technique using the poly (ƹ-caprolactone) polymer, with 0.100 g of cholecalciferol, in the ratio of polymer: drug (2: 1).The formulation had mean particle size of 269.1 nm, zeta potential of -33.0 mV, polydispersity index less than 0.22, and pH 6.0. The formulation of cholecalciferol with poly (ƹ-caprolactone) was stable after 60 days of storage. The encapsulation efficiency was approximately 98%, the images obtained by scanning electron microscopy revealed spherical shape with smooth surface and homogeneity of the nanoparticles. The results obtained by X-ray diffraction reveal a decrease in the crystallinity of the drug encapsulated in the nanostructured system. Fourier transform infrared spectroscopy was identified by bands that there were no chemical interactions between the drug and the polymer used, but the encapsulation of cholecalciferol was demonstrated. Thermogravimetric analysis revealed the melting peaks of the drug and polymer and also the temperatures of their degradation. The result of the in vitro skin permeation demonstrated the polymeric nanoparticles 21.5% cholecalciferol permeation. Thus, the use of polymeric nanoparticles can be a promising strategy in the replacement of cholecalciferol through topical application to promote appropriate levels to the human health.