In vitro Study on Synergistic Interactions Between Free and Encapsulated Q-Griffithsin and Antiretrovirals Against HIV-1 Infection

Farnaz Minooei,1 Joel R Fried,1 Joshua L Fuqua,2– 4 Kenneth E Palmer,3– 5 Jill M Steinbach-Rankins2– 5 1Department of Chemical Engineering, University of Louisville Speed School of Engineering, Louisville, KY, USA; 2Department of Bioengineering, University of Louisville...

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Autores principales:	Minooei F, Fried JR, Fuqua JL, Palmer KE, Steinbach-Rankins JM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	griffithsin nanoparticles electrospun fibers antiretrovirals synergy hiv-1 prevention microbicide Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1d9444939ae2415880bfd7ad7c0a423b
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spelling	oai:doaj.org-article:1d9444939ae2415880bfd7ad7c0a423b2021-12-02T16:00:02ZIn vitro Study on Synergistic Interactions Between Free and Encapsulated Q-Griffithsin and Antiretrovirals Against HIV-1 Infection1178-2013https://doaj.org/article/1d9444939ae2415880bfd7ad7c0a423b2021-02-01T00:00:00Zhttps://www.dovepress.com/in-vitro-study-on-synergistic-interactions-between-free-and-encapsulat-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Farnaz Minooei,1 Joel R Fried,1 Joshua L Fuqua,2– 4 Kenneth E Palmer,3– 5 Jill M Steinbach-Rankins2– 5 1Department of Chemical Engineering, University of Louisville Speed School of Engineering, Louisville, KY, USA; 2Department of Bioengineering, University of Louisville Speed School of Engineering, Louisville, KY, USA; 3Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA; 4Center for Predictive Medicine, University of Louisville, Louisville, KY, USA; 5Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USACorrespondence: Jill M Steinbach-RankinsDepartment of Bioengineering, University of Louisville Speed School of Engineering, 505 S. Hancock St., Room 623, Louisville, KY, 40202, USATel +1 502-852-5486Email jmstei01@louisville.eduIntroduction: Human immunodeﬁciency virus (HIV) remains a persistent global challenge, impacting 38 million people worldwide. Antiretrovirals (ARVs) including tenofovir (TFV), raltegravir (RAL), and dapivirine (DAP) have been developed to prevent and treat HIV-1 via different mechanisms of action. In parallel, a promising biological candidate, griffithsin (GRFT), has demonstrated outstanding preclinical safety and potency against HIV-1. While ARV co-administration has been shown to enhance virus inhibition, synergistic interactions between ARVs and the oxidation-resistant variant of GRFT (Q-GRFT) have not yet been explored. Here, we co-administered Q-GRFT with TFV, RAL, and DAP, in free and encapsulated forms, to identify unique protein-drug synergies.Methods: Nanoparticles (NPs) were synthesized using a single or double-emulsion technique and release from each formulation was assessed in simulated vaginal fluid. Next, each ARV, in free and encapsulated forms, was co-administered with Q-GRFT or Q-GRFT NPs to evaluate the impact of co-administration in HIV-1 pseudovirus assays, and the combination indices were calculated to identify synergistic interactions. Using the most synergistic formulations, we investigated the effect of agent incorporation in NP-fiber composites on release properties. Finally, NP safety was assessed in vitro using MTT assay.Results: All active agents were encapsulated in NPs with desirable encapsulation efficiency (15– 100%), providing &sim; 20% release over 2 weeks. The co-administration of free Q-GRFT with each free ARV resulted in strong synergistic interactions, relative to each agent alone. Similarly, Q-GRFT NP and ARV NP co-administration resulted in synergy across all formulations, with the most potent interactions between encapsulated Q-GRFT and DAP. Furthermore, the incorporation of Q-GRFT and DAP in NP-fiber composites resulted in burst release of DAP and Q-GRFT with a second phase of Q-GRFT release. Finally, all NP formulations exhibited safety in vitro.Conclusions: This work suggests that Q-GRFT and ARV co-administration in free or encapsulated forms may improve efficacy in achieving prophylaxis.Keywords: griffithsin, nanoparticles, electrospun fibers, antiretrovirals, synergy, HIV-1 prevention, microbicideMinooei FFried JRFuqua JLPalmer KESteinbach-Rankins JMDove Medical Pressarticlegriffithsinnanoparticleselectrospun fibersantiretroviralssynergyhiv-1 preventionmicrobicideMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 1189-1206 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	griffithsin nanoparticles electrospun fibers antiretrovirals synergy hiv-1 prevention microbicide Medicine (General) R5-920
spellingShingle	griffithsin nanoparticles electrospun fibers antiretrovirals synergy hiv-1 prevention microbicide Medicine (General) R5-920 Minooei F Fried JR Fuqua JL Palmer KE Steinbach-Rankins JM In vitro Study on Synergistic Interactions Between Free and Encapsulated Q-Griffithsin and Antiretrovirals Against HIV-1 Infection
description	Farnaz Minooei,1 Joel R Fried,1 Joshua L Fuqua,2– 4 Kenneth E Palmer,3– 5 Jill M Steinbach-Rankins2– 5 1Department of Chemical Engineering, University of Louisville Speed School of Engineering, Louisville, KY, USA; 2Department of Bioengineering, University of Louisville Speed School of Engineering, Louisville, KY, USA; 3Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA; 4Center for Predictive Medicine, University of Louisville, Louisville, KY, USA; 5Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USACorrespondence: Jill M Steinbach-RankinsDepartment of Bioengineering, University of Louisville Speed School of Engineering, 505 S. Hancock St., Room 623, Louisville, KY, 40202, USATel +1 502-852-5486Email jmstei01@louisville.eduIntroduction: Human immunodeﬁciency virus (HIV) remains a persistent global challenge, impacting 38 million people worldwide. Antiretrovirals (ARVs) including tenofovir (TFV), raltegravir (RAL), and dapivirine (DAP) have been developed to prevent and treat HIV-1 via different mechanisms of action. In parallel, a promising biological candidate, griffithsin (GRFT), has demonstrated outstanding preclinical safety and potency against HIV-1. While ARV co-administration has been shown to enhance virus inhibition, synergistic interactions between ARVs and the oxidation-resistant variant of GRFT (Q-GRFT) have not yet been explored. Here, we co-administered Q-GRFT with TFV, RAL, and DAP, in free and encapsulated forms, to identify unique protein-drug synergies.Methods: Nanoparticles (NPs) were synthesized using a single or double-emulsion technique and release from each formulation was assessed in simulated vaginal fluid. Next, each ARV, in free and encapsulated forms, was co-administered with Q-GRFT or Q-GRFT NPs to evaluate the impact of co-administration in HIV-1 pseudovirus assays, and the combination indices were calculated to identify synergistic interactions. Using the most synergistic formulations, we investigated the effect of agent incorporation in NP-fiber composites on release properties. Finally, NP safety was assessed in vitro using MTT assay.Results: All active agents were encapsulated in NPs with desirable encapsulation efficiency (15– 100%), providing &sim; 20% release over 2 weeks. The co-administration of free Q-GRFT with each free ARV resulted in strong synergistic interactions, relative to each agent alone. Similarly, Q-GRFT NP and ARV NP co-administration resulted in synergy across all formulations, with the most potent interactions between encapsulated Q-GRFT and DAP. Furthermore, the incorporation of Q-GRFT and DAP in NP-fiber composites resulted in burst release of DAP and Q-GRFT with a second phase of Q-GRFT release. Finally, all NP formulations exhibited safety in vitro.Conclusions: This work suggests that Q-GRFT and ARV co-administration in free or encapsulated forms may improve efficacy in achieving prophylaxis.Keywords: griffithsin, nanoparticles, electrospun fibers, antiretrovirals, synergy, HIV-1 prevention, microbicide
format	article
author	Minooei F Fried JR Fuqua JL Palmer KE Steinbach-Rankins JM
author_facet	Minooei F Fried JR Fuqua JL Palmer KE Steinbach-Rankins JM
author_sort	Minooei F
title	In vitro Study on Synergistic Interactions Between Free and Encapsulated Q-Griffithsin and Antiretrovirals Against HIV-1 Infection
title_short	In vitro Study on Synergistic Interactions Between Free and Encapsulated Q-Griffithsin and Antiretrovirals Against HIV-1 Infection
title_full	In vitro Study on Synergistic Interactions Between Free and Encapsulated Q-Griffithsin and Antiretrovirals Against HIV-1 Infection
title_fullStr	In vitro Study on Synergistic Interactions Between Free and Encapsulated Q-Griffithsin and Antiretrovirals Against HIV-1 Infection
title_full_unstemmed	In vitro Study on Synergistic Interactions Between Free and Encapsulated Q-Griffithsin and Antiretrovirals Against HIV-1 Infection
title_sort	in vitro study on synergistic interactions between free and encapsulated q-griffithsin and antiretrovirals against hiv-1 infection
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/1d9444939ae2415880bfd7ad7c0a423b
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In vitro Study on Synergistic Interactions Between Free and Encapsulated Q-Griffithsin and Antiretrovirals Against HIV-1 Infection

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