RESUMO
The present work aimed to evaluate different Liquid Crystal Mesophases (LCM) as transdermal drug delivery systems (TDDS) for nifedipine (NFD), a lipophilic drug model. The formulations composed of water, Citrus sinensis essential oil (CSEO), PPG-5-CETETH-20, and Olive oil ester PEG-7 were obtained and characterized by polarized light microscopy (PLM), rheology, small-angle x-ray scattering (SAXS), Fourier transform infrared coupled with an attenuated total reflection accessory (FTIR-ATR) and in vitro assays: bioadhesion, drug release, skin permeation, and retention tests. As a result, changes in component proportions led to several transparent viscous systems with an anisotropic profile. PLM and SAXS proved the presence of lamellar (S1), hexagonal (S3), and lamellar + hexagonal (S2) LCM, and rheology showed a high viscoelasticity profile. LCMs were able to adhere to the skin, and S2 achieved higher adhesion strength. NFD (5 mg/mL) has not modified the organization of LCMs. Results also showed that S3 promoted higher permeation and retention and higher disorganization of stratum corneum lipids, which is the main permeation-enhancing mechanism. Thus, the formulations obtained can carry and improve drug delivery through the skin and are promising TDDS for lipophilic drug administration, such as NFD.
Assuntos
Cristais Líquidos , Preparações Farmacêuticas , Espalhamento a Baixo Ângulo , Cristais Líquidos/química , Difração de Raios X , Administração Cutânea , PeleRESUMO
Nifedipine is a potent anti-hypertensive, which is poorly orally bioavailable on account of first-pass metabolism, short half-life, and low water solubility. This study aimed to develop a microemulsified system with low surfactant concentration and to evaluate the influence of microemulsion (ME) phase behavior on skin permeation of nifedipine, as drug model. Thereafter, MEs were obtained using PPG-5-CETETH-20, oleic acid, and phosphate buffer at pH 5.0. The selected MEs were isotropic, with droplet diameters less than 10 nm, polydispersity index < 0.25, and pH between 5.0 and 5.2. MEs presented low viscosity and Newtonian behavior. SAXS results confirmed bicontinuous and oil-in-water (o/w) MEs formation. The presence of the drug promoted only very slight modifications in the ME structure. The MEs presented ability to deliver nifedipine via the transdermal route when in comparison with the control. Nevertheless, the skin permeated and retained amounts from the o/w and bicontinuous formulations did not differ significantly. The ATR-FTIR demonstrated that both formulations promoted fluidization and disorganization of lipids and increased the drug diffusion and partition coefficients in the skin. In conclusion, PPG-5-CETETH-20 MEs obtained proved to be effective skin permeation enhancers, acting by rising the coefficients of partition and diffusion of the nifedipine in the skin.
Assuntos
Nifedipino , Pele , Administração Cutânea , Emulsões/química , Nifedipino/metabolismo , Espalhamento a Baixo Ângulo , Pele/metabolismo , Tensoativos/química , Água/química , Difração de Raios XRESUMO
Aedes aegypti is currently a major public health problem. This mosquito is responsible for the spread of infectious diseases that have been causing epidemics worldwide. Surfactant-stabilized systems, such as microemulsions, liquid-crystalline precursors and liquid crystals, are promising sustained delivery formulations of hydrophilic and hydrophobic substances. These systems are biocompatible water-soluble reservoirs for N-tosylindole exhibiting biological activity against Aedes aegypti Linn. (Diptera: Culicidae) larvae. The ternary diagram displayed four regions: microemulsion (ME), liquid crystal (LC), emulsion (EM) and phase separation (PS). PLM and SAXS distinguished microemulsions, lamellar and hexagonal phase liquid crystals. The system had a lethal concentration of 50% (LC50 = 0.1 ppm, 0.36 µM) lower than pure N-tosylindole (0.24 ppm, 0.88 µM), which has limitations in aqueous media. Furthermore, the formulation displayed no toxicity to Artemia sp., a non-target organism. The system exhibited excellent larvicidal activity as an alternative to commercial larvicides that have shown resistance and toxicity to the environment by Ae. aegypti larvae due to prolonged use. In addition, a two-fold increase in potency was observed.
Assuntos
Aedes , Inseticidas , Animais , Indóis , Inseticidas/química , Inseticidas/farmacologia , Larva , Extratos Vegetais/química , Espalhamento a Baixo Ângulo , Compostos de Tosil , Difração de Raios XRESUMO
This study aims to develop in situ microemulsion-gel (ME-Gel) obtained from hydroxypropyl methylcellulose (HPMC) films for transdermal administration of Zidovudine (AZT). Firstly, HPMC films containing propylene glycol (PG) and eucalyptus oil (EO) were obtained and characterized. Later, a pseudo-ternary phase diagram composed of water, EO, tween 80 and PG was obtained and one microemulsion (ME) with a similar proportion of the film components was obtained. ME was transformed in ME-Gel by the incorporation of HPMC. Finally, HPMC films were hydrated with Tween 80 solution to yield in situ ME-Gel and its effect on AZT skin permeation was compared with HPMC film hydrated with water (F5hyd). The results showed that the ME and ME-Gel presented a droplet size of 16.79 and 122.13⯵m, respectively, polydispersity index (PDI) < 0.39 and pH between 5.10 and 5.40. The incorporation of HPMC resulted in viscosity about 2 times higher than the use of ME. The presence of AZT did not alter the formulation properties. The in situ ME-Gel promoted a two-fold increase in the permeated amount of AZT compared to F5hyd. The results suggest that it was possible to obtain an ME-Gel in situ from HPMC films and that its effect on transdermal permeation of AZT was significant.