ALOPESİ TEDAVİSİNDE KULLANILMAK ÜZERE ÜÇ BOYUTLU (3B) YAZICI İLE BARİSİTİNİB YÜKLÜ NANOSİSTEM İÇEREN MİKROİĞNELERİN TASARIMI VE İN VİTRO-EX VİVO DEĞERLENDİRİLMESİ

Abstract

Gür, B. Design and In Vitro-Ex Vivo Evaluation of microneedles containing Baricitinib Loaded Nanosystems Using 3D Printer for the Treatment of Alopecia, Hacettepe University Graduate School of Health Sciences Pharmaceutical Technology Doctor of Philosophy Thesis, Ankara, 2026. Alopecia areata (AA) is a chronic and relapsing autoimmune disorder targeting the hair follicle. To minimize the adverse effects associated with oral baricitinib (BAR) administration and enhance follicular targeting, BAR-loaded polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) nanoparticles and nanostructured lipid carriers (NLCs) were developed and incorporated into dissolving microneedles. The PCL, PLGA, and NLC systems optimized using a Box–Behnken experimental design had particle sizes of 173.1, 148.8, and 54.8 nm, respectively, with encapsulation efficiencies of 69.42%, 81.95%, and 90.26%. Nanocarrier-loaded PVP K30/PVA-based microneedles maintained structural integrity under 32 N, achieved 100% penetration through the first three layers of the Parafilm® M model, and completely dissolved in porcine skin within 30 min. In ex vivo studies using porcine ear skin, the highest follicular BAR deposition was observed with PLGA nanoparticles, whereas the highest 24-h cumulative permeation was obtained with NLCs. Microneedle application reduced BAR detection time in the receptor medium from 4 h to 30 min and increased follicular deposition by 1.69-, 1.93-, and 1.94-fold for the PCL, PLGA, and NLC systems, respectively. Among the microneedle formulations, follicular deposition was highest with PLGA NP-loaded microneedles (19.48%), followed by PCL NP-loaded microneedles (15.13%) and NLC-loaded microneedles (14.30%). Confocal microscopy images supported nanocarrier delivery to the epidermal and superficial dermal regions via the microneedle systems. In conclusion, the developed system was considered promising for local and follicular BAR targeting in the treatment of AA.