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

• Published in: AAPS PharmSciTech 2023-01, Vol.24 (1), p.53-53, Article 53
• Main Authors: Li, Haigang, Yao, JiPeng, Guo, Yong, Huo, JingJing, Zhang, Haijuan, Zhang, Zengtao, Zhao, Jinlong, Zhang, Chun
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Chitosan - metabolism; Drug Carriers - metabolism; Mice; Nanoparticles; Particle Size; Permeability; Pharmacology/Toxicology; Pharmacy; Research Article; Skin - metabolism; Skin Absorption
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-023-02509-8

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 8 h (D 8 ) and permeability coefficient (P f ) 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 8 h 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 230 μg/mL (0.08 μM) 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.