Tofacitinib Loaded Squalenyl Nanoparticles for Targeted Follicular Delivery in Inflammatory Skin Diseases

Abstract

Tofacitinib (TFB), a Janus kinase inhibitor, has shown excellent success off-label in treating various dermatological diseases, especially alopecia areata (AA). However, TFB’s safe and targeted delivery into hair follicles (HFs) is highly desirable due to its systemic adverse effects. Nanoparticles (NPs) can enhance targeted follicular drug delivery and minimize interfollicular permeation and thereby reduce systemic drug exposure. In this study, we report a facile method to assemble the stable and uniform 240 nm TFB loaded squalenyl derivative (SqD) nanoparticles (TFB SqD NPs) in aqueous solution, which allowed an excellent loading capacity (LC) of 20%. The SqD NPs showed an enhanced TFB delivery into HFs compared to the aqueous formulations of plain drug in an ex vivo pig ear model. Furthermore, the therapeutic efficacy of the TFB SqD NPs was studied in a mouse model of allergic dermatitis by ear swelling reduction and compared to TFB dissolved in a non-aqueous mixture of acetone and DMSO (7:1 v/v). Whereas such formulation would not be acceptable for use in the clinic, the TFB SqD NPs dispersed in water illustrated a better reduction in inflammatory effects than plain TFB’s aqueous formulation, implying both encouraging good in vivo efficacy and safety. These findings support the potential of TFB SqD NPs for developing a long-term topical therapy of AA.

Advanced Skin Antisepsis: Application of UVA-Cleavable Hydroxyethyl Starch Nanocapsules for Improved Eradication of Hair Follicle-Associated Microorganisms

“…Numerous previous studies show the possibility of penetration of spherical nanoparticles into hair follicles inducing an enhanced follicular transport of therapeutics [ 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ] and subsequent triggering of release by various external as well as internal trigger mechanisms. Several physical trigger mechanisms, based on diffusion [ 71 ] or infrared light [ 46 ] as well as chemical trigger mechanisms based on pH [ 72 , 73 ] or proteolysis [ 74 , 75 ] were demonstrated in previous studies.…”

Self-Assembled Amphiphilic Starch Based Drug Delivery Platform: Synthesis, Preparation, and Interactions with Biological Barriers

“…As the StNPs were aimed for various routes of administration, their stability in different pH environments such as the acidic gastric pH (1–3), the skin pH (4.5–5), , or the more common neutral pH (7.4) was a requirement for this DDS. We investigated the StNPs characteristics after 24 h incubation at some representative pH values including 2, 5, and 7.…”

Real‐world experience and long‐term evaluation of tofacitinib in refractory alopecia areata: A prospective, open‐label, single‐center study in Asian Arab population

“…Topical tofacitinib offers a safer alternative approach for patients in whom systemic tofacitinib is contraindicated or undesired. Recently, enhanced intradermal delivery of tofacitinib has been investigated with dissolving microneedle arrays 25 and squalenyl nanoparticles 26 . These innovative approaches may help to improve follicular drug delivery and minimize interfollicular permeation thereby reducing systemic drug exposure.…”