Hyaluronic-Acid-Functionalized Tofacitinib Loaded Transethosomes for Targeted Drug Delivery in Rheumatoid Arthritis.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2025-02-17 Epub Date: 2025-01-28 DOI:10.1021/acsabm.4c01743

Pavani Chowdary, Eswara Rao Puppala, Chandra Lekha Putta, Jagapathi Rao Maddila, Vishnu Pulavarthy, V V S Rajendra Prasad, Aravind Kumar Rengan

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引用次数: 0

Abstract

The Janus kinase inhibitor tofacitinib (TOF) is an FDA-approved drug for rheumatoid arthritis (RA) treatment, but its long-term oral use leads to significant systemic side effects. The present research aimed to conquer these challenges by formulating hyaluronic-acid-coated transethosomes (HA-TOF-TE), a novel system for targeted, topical delivery of TOF to reduce systemic toxicity and improve therapeutic efficacy. Transethosomes were synthesized via the cold sonication technique with HA functionalization enabling CD44 receptor-mediated targeting of inflamed synovial tissue. Optimized TOF-TE and HA-TOF-TE formulations showed particle sizes of 199.08 ± 4.2 and 151.5 ± 5.4 nm, zeta potentials of -27.1 ± 0.75 and -34.10 ± 0.89 mV, and entrapment efficiencies of 81.16 ± 0.84% and 79.19 ± 2.65%, respectively. The gels were assessed through in vitro drug release, ex vivo permeability, and in vivo effectiveness experiments using Freund's complete adjuvant (CFA) model. Ex vivo studies showed 2.02-fold and 1.61-fold increments in flux for TOF-TE and HA-TOF-TE, respectively, with superior skin retention for HA-TOF-TE. In vivo efficacy confirmed HA-TOF-TE's significant (P < 0.001) anti-inflammatory effect on arthritic rat paws, outperforming TOF-TE and FD gels. Cytokine analysis showed notable reductions in serum IL-1, IL-6, and PGE-2 levels after HA-TOF-TE treatment, closely approximating control values. Additionally, mRNA analysis demonstrated marked decreases in IL-6, CD44, and collagen II expression, indicating HA-TOF-TE's potential as an effective, targeted RA treatment, addressing the challenges of conventional TOF therapy and minimizing systemic side effects.

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464

期刊介绍： ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.