TY  - JOUR
U1  - Wissenschaftlicher Artikel
A1  - Christmann, Rebekka
A1  - Ho, Duy-Khiet
A1  - Wilzopolski, Jenny
A1  - Lee, Sangeun
A1  - Koch, Marcus
A1  - Loretz, Brigitta
A1  - Vogt, Thomas
A1  - Bäumer, Wolfgang
A1  - Schaefer, Ulrich F.
A1  - Lehr, Claus-Michael
T1  - Tofacitinib loaded squalenyl nanoparticles for targeted follicular delivery in inflammatory skin diseases
JF  - Pharmaceutics
N2  - 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.
KW  - targeted drug delivery
KW  - hair follicle
KW  - invivo allergic dermatitis mous model
KW  - follicular delivery
KW  - interfollicular delivery
KW  - nanoparticles
KW  - squalene
Y1  - 2020
UN  - https://nbn-resolving.org/urn:nbn:de:bsz:291:415-3078
SN  - 1999-4923
SS  - 1999-4923
U6  - https://doi.org/10.3390/pharmaceutics12121131
DO  - https://doi.org/10.3390/pharmaceutics12121131
VL  - 12
SP  - 1131
EP  - 1-17
ER  -