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Design and Evaluation of Continentalic Acid Encapsulated Transfersomal Gel and Profiling of its Anti-arthritis Activity

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Abstract

Rheumatoid arthritis restricts the physical ability of patients and increases the disease burden; therefore, research has always been focused on evaluating better therapeutic options. The present research aimed to design Continentalic acid (CA)–loaded transfersomes (CA-TF) embedded in Carbopol gel containing permeation enhancer (PE) for the treatment of rheumatoid arthritis. CA-TF was developed via a modified thin film hydration method and incorporated into Carbopol 934 gel containing Eucalyptus oil (EO) as PE. The fabricated CA-TF showed particle size of < 140 nm with spherical geometry, optimal encapsulation efficiency (EE), and sustained drug release pattern. CA-TF-gel along with PE (CA-TF-PE-gel) showed better ex vivo skin penetration than plain CA gel and CA-TF-gel without PE. In vivo evaluation supported improved therapeutic outcomes of CA-TF-PE-gel in terms of behavioral findings, arthritic index, and histological findings whereas biochemical assays and pro-inflammatory cytokines (TNF-α and IL-1β) showed a significant decrease in their levels. Furthermore, immunohistochemistry assay for Nrf2 and HO-1 signaling pathways showed significant improvement in the expression of the Nrf2, and HO-1 proteins to depict improvement in arthritic condition in the animal model. CA-TF-PE-gel significantly delivered CA to the diseased target site via a topical route with promising therapeutic outcomes displayed in the CFA-induced arthritic model.

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Funding

The Higher Education Commission of Pakistan provided financial support for this work through the NRPU grant (No. 9272/Federal/NRPU/R&D/HEC/2017).

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Authors and Affiliations

  1. Department of Pharmacy, Quaid-I-Azam University, Islamabad, 45320, Pakistan

    Muhammad Waseem Akram, Danish Mazhar, Iqra Afzal, Ahmad Zeb, Qurat Ul Ain, Salman Khan & Hussain Ali

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  1. Muhammad Waseem Akram
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  2. Danish Mazhar
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Contributions

Muhammad Waseem Akram: methodology, experimental work, visualization, data curation, writing original draft; Danish Mazhar: assisted in preparation, data curation, data arrangement, manuscript editing and review; Iqra Afzal: data curation, manuscript editing, review; Ahmad Zeb: investigation, assisted in animal studies and visualization; Qurat Ul Ain: validation, characterization, and manuscript editing; Salman Khan: validation, data curation, in vivo data designing; Hussain Ali: conceptualization, project administration, supervision, data curation, manuscript editing. All authors read and approved the manuscript.

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Correspondence to Hussain Ali.

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Patent Declaration

An application with application no. 405/2022 and receipt No. 220345433 has been submitted for patent approval to IPO-Pakistan (Intellectual Property Organization of Pakistan).

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Akram, M.W., Mazhar, D., Afzal, I. et al. Design and Evaluation of Continentalic Acid Encapsulated Transfersomal Gel and Profiling of its Anti-arthritis Activity. AAPS PharmSciTech 24, 192 (2023). https://doi.org/10.1208/s12249-023-02648-y

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