Nanostructured lipid carriers promote percutaneous absorption and hair follicle targeting of tofacitinib for treating alopecia areata

• DOI: 10.1016/j.jconrel.2024.06.060
• Publication Date: 2024-07-04T13:24:24Z
• Authors: Qibin Li; Yameng Wang; Qing Guo; Jie Cao; Yangjun Feng; Xue Ke
• Keywords: Drug Carriers; Mice, Inbred C3H; Alopecia Areata; Swine; Skin Absorption; Lipids; Nanostructures; Mice; Pyrimidines; Piperidines; Liposomes; Animals; Nanoparticles; Female; Hair Follicle

Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8+NKG2D+T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata.