Desenvolvimento e avaliação de formulação transdérmica contendo vitamina D3 nanoestruturada

Abstract

Vitamin D3 is synthesized in the skin on exposure to ultraviolet irradiation. Another source of the molecule is through diet. Nowadays the vitamin D deficiency is increasing worldwide; however, it presents variable oral bioavailability, which makes supplementation difficult. Vitamin D is critical for calcium homeostasis and bone health, in addition, potential extra skeletal actions have been proposed (actions in the immune system, cardiovascular system and carcinogenesis). Thus, the aim of this study was to develop an innovative transdermal formulation containing vitamin D3. For this, nanostructured lipid carriers containing vitamin D3 were produced, by the high shear homogenization and ultrasonication techniques. The nanoparticles were characterized in terms of particle size, polydispersity index, zeta potential, encapsulation efficiency, stability and morphology. In addition, cytotoxicity of the nanoparticle was evaluated in murine fibroblast cell culture. The nanostructured lipid carrier produced and the vitamin D3 (raw material) were incorporated separately into a transdermal vehicle, forming two formulations. The developed emulsions, as well as the nanoparticle, were evaluated in relation to vitamin D3 degradation, in vitro release and ex vivo permeation. The nanoparticles presented particle size suitable for topical application (192.5 ± 10.5 nm), narrow size distribution (polydispersity index = 0.13 ± 0.04), spherical shape and high absolute zeta potential value (29.0 ± 0.6 mV). Their particle size and polydispersity index remained unaltered for 15 days in refrigerator storage and for at least 30 days in storage at room temperature and 32 °C. Moreover, vitamin D3 was efficiently encapsulated in the nanoparticle (Entrapment efficiency = 99.75 ± 0.03%). The vitamin D3 nanoparticle led to decreased cytotoxicity of the molecule, to murine fibroblast (L929) cell at tested conditions. In the refrigerator storage, the nanoparticle maintained its vitamin D3 content for 7 days. The vitamin D3 emulsion (raw material) led to a decrease in the degradation under temperature of 32 °C when compared to the raw material. The incorporation of the nanoparticle in the transdermal vehicle led to a decrease in vitamin D3 degradation at all temperatures tested, when compared to the nanoparticle alone. Among the formulations, the nanoparticle was able to release the largest amount of vitamin D3. All formulations followed the Higuchi diffusion kinetic model. Both transdermal emulsions were able to promote the permeation of vitamin D3 according to daily nutritional requirements.