Preparation of Conotoxin-Encapsulated Chitosan Nanoparticles and Evaluation of Their Skin Permeability.

Abstract

μ-Conotoxin CnIIIC (conotoxin, CTX)-loaded chitosan nanoparticles (CTX-NPs) were prepared using the ionic cross-linking method. The CTX-NPs were spherical and well with a polydispersity index of 0.292 ± 0.039, drug loading efficiency of 25.9 ± 1.2%, and encapsulation efficiency of 95.6 ± 1.3%. In vitro release studies showed that the release behavior of CTX-NPs in a pH 5.0 acetate buffer followed zero-order kinetics. In vitro transdermal experiments using Franz diffusion cells mounted with mouse abdominal skin demonstrated that the cumulative intradermal deposition amount of CTX per unit area in 8h (D8) and permeability coefficient (Pf) of CTX loaded on CTX-NPs were 2.30- and 7.71-times that of the CTX solution. In vivo transdermal experiments in mice showed that the amount of CTX deposited in the skin after 8h of CTX saline administration was significantly lower than that of CTX deposited in the skin after administration of CTX-NPs. In vitro fluorescence labeling transdermal studies through Franz diffusion cells mounted with mouse abdominal skin indicated that CTX-NPs aggregated at hair follicles. Skin irritation tests in mice indicated that the irritation due to CTX-NPs was negligible. The cytotoxicity experiment showed that the viability of Balb/c 3T3 cells with CTX-NPs containing 230μg/mL (0.08μM) CTX was greater than 75%. CTX-NPs increase intradermal deposition of CTX by accumulating in hair follicles, which has positive implications for transdermal penetration of CTX.