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

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...

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Main Authors: Karamot O. Oyediran, Ibilola M. Cardoso-Daodu, Peace Ofonabasi Bassey, Deborah A. Ogundemuren, Ridwan Muhammed, Olusola E. Ojo, Andrew N. Amenaghawon, Chukwuemeka P. Azubuike, Rachna Agarwal, Kondoru Haritha, Margaret O. Ilomunaya
Format: Article
Language:English
Published: Elsevier 2025-12-01
Series:Pharmaceutical Science Advances
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Online Access:http://www.sciencedirect.com/science/article/pii/S2773216925000170
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author Karamot O. Oyediran
Ibilola M. Cardoso-Daodu
Peace Ofonabasi Bassey
Deborah A. Ogundemuren
Ridwan Muhammed
Olusola E. Ojo
Andrew N. Amenaghawon
Chukwuemeka P. Azubuike
Rachna Agarwal
Kondoru Haritha
Margaret O. Ilomunaya
author_facet Karamot O. Oyediran
Ibilola M. Cardoso-Daodu
Peace Ofonabasi Bassey
Deborah A. Ogundemuren
Ridwan Muhammed
Olusola E. Ojo
Andrew N. Amenaghawon
Chukwuemeka P. Azubuike
Rachna Agarwal
Kondoru Haritha
Margaret O. Ilomunaya
author_sort Karamot O. Oyediran
collection DOAJ
description 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 Box-Behnken 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 ​± ​0.65 ​cP, flux 9806 μg/cm2/h for TNF with a drug release of 119, 205.6 μg/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.
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spelling doaj-art-2739d446564c4e558b49e14091e12eff2025-08-20T03:33:08ZengElsevierPharmaceutical Science Advances2773-21692025-12-01310007910.1016/j.pscia.2025.100079Artificial neural network guided optimization of tenofovir and Cyanovirin-N multipurpose preventive hydrogel formulation developed using the Box Behnken design modelKaramot O. Oyediran0Ibilola M. Cardoso-Daodu1Peace Ofonabasi Bassey2Deborah A. Ogundemuren3Ridwan Muhammed4Olusola E. Ojo5Andrew N. Amenaghawon6Chukwuemeka P. Azubuike7Rachna Agarwal8Kondoru Haritha9Margaret O. Ilomunaya10Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, PMB 12003, Lagos, Nigeria; Corresponding author.Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, PMB 12003, Lagos, NigeriaDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, PMB 12003, Lagos, NigeriaDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, PMB 12003, Lagos, NigeriaDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, PMB 12003, Lagos, Nigeria; MEDAFRICA GMP Laboratory, Faculty of Pharmacy University of Lagos, PMB 12003, Lagos, NigeriaDepartment of Metallurgical and Materials Engineering, Faculty of Engineering, University of Lagos, Lagos, NigeriaDepartment of Chemical Engineering, Faculty of Engineering, University of Benin, Benin City, NigeriaDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, PMB 12003, Lagos, NigeriaBhabha Atomic Research Centre Mumbai, 400085, India; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, 400 094, IndiaBhabha Atomic Research Centre Mumbai, 400085, India; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, 400 094, IndiaDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, PMB 12003, Lagos, Nigeria; MEDAFRICA GMP Laboratory, Faculty of Pharmacy University of Lagos, PMB 12003, Lagos, Nigeria; Corresponding author. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, PMB 12003, Lagos, Nigeria.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 Box-Behnken 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 ​± ​0.65 ​cP, flux 9806 μg/cm2/h for TNF with a drug release of 119, 205.6 μg/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.http://www.sciencedirect.com/science/article/pii/S2773216925000170Box Behnken designArtificial neural networkHydrogelsCyanovirin-NTenofovirFlux
spellingShingle Karamot O. Oyediran
Ibilola M. Cardoso-Daodu
Peace Ofonabasi Bassey
Deborah A. Ogundemuren
Ridwan Muhammed
Olusola E. Ojo
Andrew N. Amenaghawon
Chukwuemeka P. Azubuike
Rachna Agarwal
Kondoru Haritha
Margaret O. Ilomunaya
Artificial neural network guided optimization of tenofovir and Cyanovirin-N multipurpose preventive hydrogel formulation developed using the Box Behnken design model
Pharmaceutical Science Advances
Box Behnken design
Artificial neural network
Hydrogels
Cyanovirin-N
Tenofovir
Flux
title Artificial neural network guided optimization of tenofovir and Cyanovirin-N multipurpose preventive hydrogel formulation developed using the Box Behnken design model
title_full Artificial neural network guided optimization of tenofovir and Cyanovirin-N multipurpose preventive hydrogel formulation developed using the Box Behnken design model
title_fullStr Artificial neural network guided optimization of tenofovir and Cyanovirin-N multipurpose preventive hydrogel formulation developed using the Box Behnken design model
title_full_unstemmed Artificial neural network guided optimization of tenofovir and Cyanovirin-N multipurpose preventive hydrogel formulation developed using the Box Behnken design model
title_short Artificial neural network guided optimization of tenofovir and Cyanovirin-N multipurpose preventive hydrogel formulation developed using the Box Behnken design model
title_sort artificial neural network guided optimization of tenofovir and cyanovirin n multipurpose preventive hydrogel formulation developed using the box behnken design model
topic Box Behnken design
Artificial neural network
Hydrogels
Cyanovirin-N
Tenofovir
Flux
url http://www.sciencedirect.com/science/article/pii/S2773216925000170
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