Development and Characterization of Brain Targeted Niosomal Formulations of Emtricitabine to treat HIV Associated CNS Disorders

Abstract

Formulations of drug-free niosomes were prepared by four different methods (Thin layer evaporation-vortex, Thin layer evaporation-paddle, Reverse phase evaporation method and Proniosome method) using two surfactants, Span 60 and Span 40 with cholesterol and Solulan C24. Variations were made in the molar ratios and the total concentration of lipid components. Among all the formulations niosomes prepared by TLE-vortex and TLE-paddle methods produced narrow sized niosomal dispersions. It was found that vesicles formulated with Span alone yielded comparatively larger niosomes than those with cholesterol and Solulan added to it. Since, small unilamellar vesicles exhibit prolonged plasma concentrations with more entrapment of aqueous phase compared with that of large unilamellar and multilamellar vesicles, two widely used size reduction methods (sonication and size extrusion) were carried out. Among the two methods of size reduction employed, probe sonication was found to be more satisfactory in reducing the vesicle size by approximately two times than that of size extrusion method for all formulations. The suitability of the drug at different hydration temperatures was evaluated by subjecting the drug solution to 65±50C and 90±50C. The results showed that the drug is stable and can be subjected to such temperatures. Based on the results of mean particle size, formulations containing Span 60 and Span 40 with a total molar concentration of 38mM in the molar ratio of Span: CHL : SOL : NPG as 50 : 40 : 10 : 10 prepared by TLE-vortex and TLE-paddle were selected as the optimized formulations. The NPG drug-free niosomes were prepared by varying the hydration temperatures of 65±50C and 90±50C and the hydration temperature was optimized to 65±50C. Emtricitabine is nucleoside reverse transcriptase inhibitor used in the treatment of HIV patients. The drug is an intermediate CNS penetrating drug. So, the effective concentration of the drug required to reduce the viral load in the CSF of HIV patients is not attained.