Development of Proniosome Gel Formulation for CHIKV Infection

Author:

Altay Benetti Ayça1ORCID,Thwin Ma Thinzar1ORCID,Suhaimi Ahmad2ORCID,Liang Ryan Sia Tze1,Ng Lisa Fong-Poh2,Lum Fok-Moon2ORCID,Benetti Camillo1ORCID

Affiliation:

1. Department of Pharmacy and Pharmaceutical Sciences, National University of Singapore, Singapore 117544, Singapore

2. A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore

Abstract

Given the increasing aging population and the rising prevalence of musculoskeletal diseases due to obesity and injury, urgent research is needed to formulate new treatment alternatives, as current options remain inadequate. Viruses can exacerbate arthritis and worsen symptoms in patients with pre-existing osteoarthritis. Over the past decade, the chikungunya virus (CHIKV) has emerged as a significant public health concern, especially in Asia and South America. Exploring natural products, such as berberine, has shown promise due to its anticatabolic, antioxidative, and anti-inflammatory effects. However, berberine’s low stability and bioavailability limit its efficacy. We hypothesized that encapsulating berberine into a proniosome gel, known for its ease of preparation and stability, could enhance its bioavailability and efficacy when applied topically, potentially treating CHIKV infection. Our investigation focused on how varying berberine loads and selected excipients in the proniosome gel influenced its physical properties, stability, and skin permeability. We also examined the biological half-life of berberine in plasma upon topical administration in mice to assess the potential for controlled and sustained drug release. Additionally, we analyzed the antioxidant stress activity and cell viability of HaCaT keratinocytes and developed a lipopolysaccharide-stimulated cell culture model to evaluate anti-inflammatory effects using pro-inflammatory cytokines. Overall, the research aims to transform the treatment landscape for arthritis by leveraging berberine’s therapeutic potential.

Funder

National University of Singapore

Singapore National Medical Council

Open-Fund Young Investigator Research Grant

Singapore Biomedical Research Council (BMRC) Central Research Fund

Publisher

MDPI AG

Reference80 articles.

1. World Health Organization (2024, June 03). Musculoskeletal Health Conditions. Available online: https://www.who.int/news-room/fact-sheets/detail/musculoskeletal-conditions.

2. Mayo Foundation for Medical Education and Research (2024, June 03). Osteoarthritis. Mayo Clinic. Available online: https://www.mayoclinic.org/diseases-conditions/osteoarthritis/symptoms-causes/syc-20351925.

3. (2024, June 03). Osteoarthritis in 2020 and beyond: A Lancet Commission. Available online: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32230-3/fulltext.

4. Centers for Disease Control and Prevention (2024, June 03). Osteoarthritis (OA). 27 July 2020, Available online: https://www.cdc.gov/arthritis/docs/oaagenda2020.pdf.

5. Pathak, H., Mohan, M.C., and Ravindran, V. (2024, June 03). Chikungunya Arthritis, Available online: www.cdc.gov/chikungunya/.

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