Desenvolvimento de nanopartículas lipídicas e associação de iontoforese para administração transdérmica do lopinavir
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2020-03-30
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Universidade Federal de Goiás
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Introduction: Lopinavir (LPV) is one of the antiretrovirals used to combat the human immunodeficiency virus (HIV). It has low oral bioavailability, a complex therapeutic regimen, and adverse effects, which affect the efficiency of the therapy. Transdermal administration can circumvent or reduce these problems. However, it requires strategies that facilitate the permeation of the drug. It is believed that nanostructured lipid carriers (NLC) combined with iontophoresis can increase the permeation of LPV to the deeper layers of the skin to be absorbed systemically. Objective: Develop NLC containing LPV and evaluate the permeation of the drug with and without iontophoresis. Methodology: The analytical method was adapted and validated. The solubility of the drug in surfactants was evaluated to select those that most solubilize LPV. NLC with different concentrations of LPV (0.5 - 1.5 mg/mL) were produced. Full characterization was performed (mean diameter, polydispersity index (PdI), zeta potential, encapsulation efficiency (EE), recovery (REC), drug loading (DL), and morphology). Electrical stability studies of the drug and NLC were carried out, as well as studies of electronic paramagnetic resonance (EPR), release and permeation in vitro, with and without electric current. Results and discussion: The method was linear, precise, and accurate. The NLC was spherical (145.83 ± 5.229 to 179 ± 2.551 nm). The PdI and zeta potential indicated good homogeneity and stability of the NLC. EE was around 80%, and, therefore, particles with 1.5 mg/mL of LPV were selected for subsequent studies. The stability studies of NLC-LPV concerning electric current demonstrated that the application of iontophoresis significantly reduced EE. The EPR spectra showed a significant increase in the nanoparticles' stiffness when an electrical current was applied. The electrical current also significantly increased the drug release in 6 h study compared to studies without electrical current. These data demonstrate that the electric current is a trigger in the drug release since it increases the rigidity of the lipid matrix. Iontophoresis also significantly increased the permeation of LPV. With an electrical current, LPV quantification was 14,49 ± 3,98 and 21,85 ± 2,28 μg after cathodic and anodic iontophoresis. These permeation data are significantly higher than the drug's EC50 values for various strains of the virus, reported in the literature. Conclusion: The combination of iontophoresis with NLC enabled higher permeation of LPV and proved to be a promising strategy
for transdermal drug administration. However, in vivo, and pharmacokinetic studies are needed to assess the effectiveness of the strategy used in this study.
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MOURA, R. B. P. Desenvolvimento de nanopartículas lipídicas e associação de iontoforese para administração transdérmica do lopinavir. 2020. 55 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2020.