Fabrication of PEGylated elastic bilosomes as a potentially effective transdermal delivery of celecoxib for management of osteoarthritis: In vitro characterization, statistical optimization, Ex vivo and In vivo assessments

Abstract

Celecoxib (CLX) is a potent non-steroidal anti-inflammatory drug (NSAID) that is utilized to manage osteoarthritis (OA). CLX has low oral bioavailability due to its extensive first-pass effect and low water solubility. Moreover, long-term treatment regimens with oral NSAIDs cause systemic side effects. This study aimed to develop PEGylated elastic bilosomes (PEBs) for transdermal delivery of CLX to avoid all its drawbacks and enhance its therapeutic efficacy. CLX-PEBs were prepared utilizing a thin-film hydration technique based on a 2⁴ full factorial design. The optimized PEB (OPEB) formula is composed of PEGylated surfactant (Brij® 721), Span 60: Cholesterol (5:3), and 5 mg sodium cholate. It showed the minimum vesicle size (167.40 ± 2.39 nm) and polydispersity index (0.371 ± 0.008), and the maximum entrapment efficiency (86.12 ± 1.27 %), zeta potential (−39.20 ± 4.94 mV), and % released after 24 h (66.97 ± 2.75 %). The OPEB formula was converted to OPEB gel that was subjected to ex vivo permeation and in vivo assessments. The OPEB gel boosted CLX permeation with 1.75 and 3.27-fold compared to conventional bilosomal gel and free celecoxib gel, respectively. The in vivo studies revealed that the OPEB gel achieved a significant reduction in the right knee joint edema, knee joint degradation-related biomarkers, TGF-β, IGF-1, and pro-inflammatory mediators compared to oral suspension and drug gel. Histopathological data confirmed the reduction in osteoarthritic deterioration and the maintenance of joint integrity, indicating the efficacy of association in cartilage regeneration. Therefore, PEBs might be regarded as a potentially effective approach for transdermal delivery of CLX to manage OA. The promising outcomes of our OPEB gel in the rat osteoarthritis model highlight the need for further human clinical studies to assess the OPEB gel's safety and efficacy as a potential alternative dosage form to existing osteoarthritis therapies.