Characterization ex vivo skin permeation and pharmacological studies of ibuprofen lysinate-chitosan-gold nanoparticles

Abstract

Chitosan-gold nanoparticles (CS-AuNPs), at different molar ratios (1:1, 1:2, 1:4 and 1:6) of chloroauric acid (HAuCl4) to chitosan (CS), were prepared at room temperature. The CS-AuNP 1:6 ratio showed pronounced physical stability. The results indicated a shift in wavelength of maximum absorbance (λmax) as the CS-AuNPs ratio changes from 1:1 to 1:6. The mean particle size and zeta potential for the optimal CS-AuNPs molar ratio1:6 were 37.5 nm and +40.5 mV, respectively. The chemical interaction of ibuprofen lysinate (IBL) with the surface of CS-AuNPs was then investigated to develop a novel skin delivery system with enhanced pharmacological activity. It was demonstrated that at IBL concentration (>4.5 mg/ml) a significant change in the composition of the surface of the CS-AuNPs (1:6) was detected leading to a tremendous decrease in the zeta potential and an increase in the aggregate particle size. The negatively charged carboxylate groups of IBL could neutralize the positively charged surface of the CS-AuNPs and hence leading to a significant decrease in the repulsion between the aggregates. Accordingly, zeta potential values drastically decreased which resulted in particle coagulation. Intermolecular interactions between the IBL and CS at the surface of CS-AuNPs were detected with several experimental techniques such as particle size, zeta potential, surface tension and FTIR. Fortunately, a rapid and significant increase in skin permeation of IBL (3 mg/ml) loaded CS-AuNPs was also detected which was several times faster than that of CS/IBL complex, or single IBL (control). The pharmacological activity was also evaluated using Eddy's hotplate method and carrageenan-induced edema model on mice and the results indicated significant enhancement in the analgesic and anti-inflammatory effects of IBL (3 mg/ml) loaded CS-AuNPs.