RESUMO
Hexagonal liquid crystals and supramolecular polymers from meglumine-based supra-amphiphiles were developed as drug delivery systems to be applied on the skin. The influence of fatty acid unsaturation on the structure and mechanical properties was evaluated. Moreover, we have investigated the system biocompatibility and how the type of water could influence its bioadhesive properties. Meglumine-oleic acid (MEG-OA) was arranged as hexagonal liquid crystals at 30-70â¯wt% water content, probably due to its curvature and increased water solubility. Meglumine-stearic acid (MEG-SA) at 10-80â¯wt% water content self-assembled as a lamellar polymeric network, which can be explained by the low mobility of MEG-SA in water due to hydrophobic interactions between fatty acid chains and H-bonds between meglumine and water molecules. Both systems have shown suitable mechanical parameters and biocompatibility, making them potential candidates to encapsulate therapeutic molecules for skin delivery. Moreover, a strong positive correlation between the amount of unfrozen bound water in meglumine-based systems and the bioadhesion properties was observed. This work shows that a better understanding of the physicochemical properties of a drug delivery system is extremely important for the correlation with the desired biological response and, thus, improve the product performance for biomedical applications.
Assuntos
Sistemas de Liberação de Medicamentos , Meglumina/química , Pele/química , Tensoativos/química , Água/química , Adesão Celular , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Meglumina/síntese química , Meglumina/farmacologia , Tamanho da Partícula , Relação Estrutura-Atividade , Propriedades de Superfície , Tensoativos/síntese química , Tensoativos/farmacologia , ViscosidadeRESUMO
The need for daily parenteral administration represents one of the most serious limitations in the clinical use of pentavalent antimonials against leishmaniasis. In this work, we investigated the ability of beta-cyclodextrin to enhance the oral absorption of antimony and to promote the oral efficacy of meglumine antimoniate against experimental cutaneous leishmaniasis. The occurrence of interactions between beta-cyclodextrin and meglumine antimoniate was demonstrated through the changes induced in the spin lattice relaxation times of protons in both compounds. When free and complexed meglumine antimoniate were given orally to Swiss mice, plasma antimony levels were found to be about three times higher for the meglumine antimoniate-beta-cyclodextrin complex than for the free drug. Antileishmanial efficacy was evaluated in BALB/c mice experimentally infected with Leishmania amazonensis. Animals treated daily with the complex (32 mg of Sb/kg of body weight) by the oral route developed significantly smaller lesions than those treated with meglumine antimoniate (120 mg of Sb/kg) and control animals (treated with saline). The effectiveness of the complex given orally was equivalent to that of meglumine antimoniate given intraperitoneally at a twofold-higher antimony dose. The antileishmanial efficacy of the complex was confirmed by the significantly lower parasite load in the lesions of treated animals than in saline-treated controls. This work reports for the first time the effectiveness of an oral formulation for pentavalent antimonials.