Artificial neural network guided optimization of tenofovir and Cyanovirin-N multipurpose preventive hydrogel formulation developed using the Box Behnken design model

Abstract

Tenofovir (TNF) is an antiretroviral drug that has being used as a topical microbicide to prevent human immunodeficiency virus transmission (HIV). Cyanovirin-N (CV-N) is a lectin protein that can bind to the HIV envelope glycoprotein and inhibit viral entry. The combination of TNF and CV-N may have synergistic effects and enhance the efficacy of microbicide. The aim of this study was to develop and optimize composite hydrogel formulations containing 1%TNF and 0.0005% CV-N using Box Behnken Design. A three-factor, three-level BoxBehnken design was employed to investigate the effects of the concentrations of PEG₂₀₀₀, sodium carboxyl methylcellulose (NaCMC), and calcium chloride on the release of Tenofovir, flux, and mucoadhesion. The mucoadhesion was evaluated by measuring the percent mucin adsorption while flux and release kinetics were evaluated using the Franz cell diffusion method. The optimal hydrogel formulation was found to contain 4% NaCMC, 2% PEG2000 and 1% CaCl₂. The hydrogel had a pH of 4.5±0.017, a viscosity of 275600±0.65cP, flux 9806μ g/cm²/h for TNF with a drug release of 119, 205.6μ g/cm². The TNF gel exhibited a pseudoplastic rheological behavior with 96.3% muco-adhesion. The study successfully developed an optimized TNF/CV-N mucoadhesive hydrogel, highlighting its potential as an on-demand multipurpose prevention technology (MPT) for HIV. The formulation was optimized to ensure good drug release, flux and mucoadhesion. The optimized hydrogel offers a convenient, effective method for preventing sexually transmitted infections (STIs), addressing critical challenges in drug delivery and user adherence while advancing public health strategies for STIs.

Keywords

Box Behnken design / Artificial neural network / Hydrogels / Cyanovirin-N / Tenofovir / Flux

CRediT authorship contribution statement

Karamot O. Oyediran: Writing - review & editing, Writing - original draft, Visualization, Validation, Resources, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Ibilola M. Cardoso-Daodu: Writing - review & editing. Peace Ofonabasi Bassey: Writing - review & editing. Deborah A. Ogundemuren: Writing - review & editing, Conceptualization. Ridwan Muhammed: Writing - review & editing. Olusola E. Ojo: Visualization. Andrew N. Amenaghawon: Writing - original draft, Methodology, Data curation. Chukwuemeka P. Azubuike: Writing - review & editing, Supervision. Rachna Agarwal: Writing - review & editing, Conceptualization. Kondoru Haritha: Writing - review & editing. Margaret O. Ilomunaya: Writing - review & editing, Supervision, Resources, Methodology, Conceptualization.

Consent for publication

Not applicable.

Availability of data and material

The datasets used during the current study are available from the corresponding author on request.

Declaration of generative AI in scientific writing

The authors acknowledge the use of Image J, Canva, DPI converter to enhance images in this manuscript. ChatGPT was also used to summarize certain sentences. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.

Cyanovirin-N was generously supplied by the BARC group, Mumbai, India. Financial support and access to Electospinnig equipment was provided by the MEDAFRICA GMP Laboaratory, Faculty of Pharmacy University of Lagos Nigeria.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgement

Cyanovirin-N was generously supplied by the BARC group, Mumbai, India. Financial support and access to the NLI Electrospinnig equipment was provided by the MEDAFRICA GMP Laboratory, Faculty of Pharmacy University of Lagos Nigeria. The authors acknowledge the support of the entire staff of Pharmaceutics and Pharmaceutical technology, Faculty of Pharmacy, University of Lagos

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.pscia.2025.100079.

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