Pectin-based hydrogel loaded with polymeric nanocapsules for the cutaneous delivery of tacrolimus: A targeted approach for the treatment of psoriasis

Author(s)

Gomes, G. S. ; Benin, T. ; Ferreira, E. C. J. ; Palma, V. M. ; Alves, A. C. S. ; Visioli, F. ; Longhi, M. S. ; Pohlmann, A. R. ; Guterres, S. S. ; Frank, L. A.

• Document type: Journal article
• Source: JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY; v. 99, p. 13-pg., 2024-07-24.

Abstract

This study aimed to develop a novel pectin-based hydrogel (PEC) incorporating nanocapsules-loaded tacrolimus (NCtac), named PEC-NCtac, as a potential strategy for psoriasis treatment. Blank nanocapsules (NC), PEC, PECNC, non-encapsulated tacrolimus (TAC), and the commercial TAC ointment (Tacroz (R)) were used as controls. The objectives involved physicochemical characterizing PEC-NCtac, assessing its cytotoxicity and anti-inflammatory effects, comparing adhesiveness with controls, determining skin penetration and permeation, and evaluating irritation potential. PEC-NCtac had an unimodal size distribution by laser diffraction (mean diameter of 250 nm and polydispersity -SPAN- of 1.68), drug content of 0.81 mg g- 1 (HPLC), and pH of 4.51 (potentiometry). The nanoformulation had no significant impact on the viability of HaCat cells and CD4+ T cells when tested 24 h after treatment, with both cell types maintaining nearly 100% viability. Treatment with NCtac resulted in a reduction in the pro-inflammatory cytokine IL-17A (p < 0.05). Adhesion studies revealed that PEC-NC showed a 1.9-fold higher force work compared to PEC. The combined effect of individual adhesion of NC and PEC when associated (PEC-NC) was evident in both healthy and injured skin (Healthy skin = 73 mN mm; Injured skin = 251 mN mm). PEC-NCtac allowed a decrease in skin drug permeation in the epidermis of injured skin compared to Tacroz (R) (40 % vs. 70 %, respectively). PEC-NCtac exhibited non-irritating activity in the HET-CAM/CAM-TBS model, while TAC demonstrated slight irritant activity. Furthermore, PEC-NCtac showed superior anti-inflammatory effects compared to TAC (75.0 % vs. 58 %, P value = 0.03). Summarizing, PEC-NCtac appears promising for topical treatment, demonstrating enhanced adhesion, skin penetration, safety profile, and anti-inflammatory activity. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants