title: Griffithsin-Modified Electrospun Fibers as a Delivery Scaffold To Prevent HIV Infection.
abstract: Despite current prophylactic strategies, sexually transmitted infections (STIs) remain significant contributors to global health challenges, spurring the development of new multipurpose delivery technologies to protect individuals from and treat virus infections. However, there are few methods currently available to prevent and no method to date that cures human immunodeficiency virus (HIV) infection or combinations of STIs. While current oral and topical preexposure prophylaxes have protected against HIV infection, they have primarily relied on antiretrovirals (ARVs) to inhibit infection. Yet continued challenges with ARVs include user adherence to daily treatment regimens and the potential toxicity and antiviral resistance associated with chronic use. The integration of new biological agents may avert some of these adverse effects while also providing new mechanisms to prevent infection. Of the biologic-based antivirals, griffithsin (GRFT) has demonstrated potent inhibition of HIV-1 (and a multitude of other viruses) by adhering to and inactivating HIV-1 immediately upon contact. In parallel with the development of GRFT, electrospun fibers (EFs) have emerged as a promising platform for the delivery of agents active against HIV infection. In the study described here, our goal was to extend the mechanistic diversity of active agents and electrospun fibers by incorporating the biologic GRFT on the EF surface rather than within the EFs to inactivate HIV prior to cellular entry. We fabricated and characterized GRFT-modified EFs (GRFT-EFs) with different surface modification densities of GRFT and demonstrated their safety and efficacy against HIV-1 infection in vitro We believe that EFs are a unique platform that may be enhanced by incorporation of additional antiviral agents to prevent STIs via multiple mechanisms.
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Tiffany N
authors.initials: TN
authors.lastname: Grooms
authors.affiliation: Department of Biochemistry, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Hung R
authors.initials: HR
authors.lastname: Vuong
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Tyo
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Danial A
authors.initials: DA
authors.lastname: Malik
authors.affiliation: Department of Bioengineering, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Lee B
authors.initials: LB
authors.lastname: Sims
authors.affiliation: Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Carli P
authors.initials: CP
authors.lastname: Whittington
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, USA.|Center for Predictive Medicine, University of Louisville, Louisville, Kentucky, USA.|Owensboro Cancer Research Program at University of Louisville James Graham Brown Cancer Center, Owensboro, Kentucky, USA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Palmer
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, USA N.Matoba@louisville.edu Jill.Steinbach@louisville.edu.|Owensboro Cancer Research Program at University of Louisville James Graham Brown Cancer Center, Owensboro, Kentucky, USA.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Matoba
authors.affiliation: Department of Bioengineering, University of Louisville, Louisville, Kentucky, USA N.Matoba@louisville.edu Jill.Steinbach@louisville.edu.|Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, USA.|Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.|Center for Predictive Medicine, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Steinbach-Rankins
mesh_terms: D020418:Algal Proteins / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002584:Cervix Uteri / Q000166:cytology; D016503:Drug Delivery Systems / Q000379:methods*; D055664:Electrochemical Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D037121:Plant Lectins / Q000737:chemistry / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014621:Vagina / Q000166:cytology; D053585:Virus Attachment / Q000187:drug effects*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D020418:Algal Proteins; D000998:Antiviral Agents; D037121:Plant Lectins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008156:Luciferases; D001616:beta-Galactosidase; C499654:griffithsin protein, Griffithsia