Publication Database

Tofacitinib loaded squalenyl nanoparticles for targeted follicular delivery in inflammatory skin diseases (2020)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Christmann, Rebekka

Ho, Duy-Khiet

Wilzopolski, Jenny (WE 14)

Lee, Sangeun

Koch, Marcus

Loretz, Brigitta

Vogt, Thomas

Bäumer, Wolfgang (WE 14)

Schaefer, Ulrich F.

Lehr, Claus-Michael

Quelle

Pharmaceutics

Bandzählung: 12

Heftzählung: 12

Seiten: 1131

ISSN: 1999-4923

Sprache

Englisch

Verweise

URL (Volltext): https://www.mdpi.com/1999-4923/12/12/1131

DOI: 10.3390/pharmaceutics12121131

Pubmed: 33255225

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.