Multipurpose Tenofovir Disoproxil Fumarate Electrospun Fibers for the Prevention of HIV-1 and HSV-2 Infections in Vitro

Overview

Journal Int J Pharm

Specialties Chemistry
Pharmacology

Date 2017 Aug 12

PMID 28797967

Citations 12

Authors

Kevin M Tyo

Hung R Vuong

Danial A Malik

Lee B Sims

Houda Alatassi

Jinghua Duan

Walter H Watson

Jill M Steinbach-Rankins

Affiliations

Soon will be listed here.

Abstract

Sexually transmitted infections affect hundreds of millions of people worldwide. Both human immunodeficiency virus (HIV-1 and -2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir disoproxil fumarate (TDF), exhibited sustained-release for up to 4 weeks, and provided complete in vitro protection against HSV-2 and HIV-1 for 24h and 1 wk, respectively, based on the doses tested. In vitro cell culture and EpiVaginal tissue tests confirmed the safety of fibers in vaginal and cervical cells, highlighting the potential of PLGA and PLCL EFs as multipurpose next-generation drug delivery vehicles.

Citing Articles

Electrospun nanofibers: Focus on local therapeutic delivery targeting infectious disease.

Kyser A, Fotouh B, Harris V, Patel R, Maners C, Frieboes H J Drug Deliv Sci Technol. 2025; 104.

PMID: 39802685 PMC: 11720493. DOI: 10.1016/j.jddst.2024.106520.

Development and characterization of formulations based on combinatorial potential of antivirals against genital herpes.

Gaikwad M, George A, Sivadas A, Karunakaran K, N S, Byradeddy S Naunyn Schmiedebergs Arch Pharmacol. 2024; .

PMID: 39347802 DOI: 10.1007/s00210-024-03468-y.

Mesh and layered electrospun fiber architectures as vehicles for Lactobacillus acidophilus and Lactobacillus crispatus intended for vaginal delivery.

Minooei F, Kanukunta A, Mahmoud M, Gilbert N, Lewis W, Lewis A Biomater Adv. 2023; 154:213614.

PMID: 37659215 PMC: 10873095. DOI: 10.1016/j.bioadv.2023.213614.

Rapid-dissolving electrospun nanofibers for intra-vaginal antibiotic or probiotic delivery.

Minooei F, Gilbert N, Zhang L, Sarah NeCamp M, Mahmoud M, Kyser A Eur J Pharm Biopharm. 2023; 190:81-93.

PMID: 37479065 PMC: 10530173. DOI: 10.1016/j.ejpb.2023.07.009.

Strategic actions to advance multipurpose prevention technologies in low- and middle-income countries.

Young Holt B, van der Straten A, Barker T, Chirenje Z, Cameron A, Scott C Front Reprod Health. 2023; 5:1150857.

PMID: 37465533 PMC: 10351869. DOI: 10.3389/frph.2023.1150857.

References

Galvin S, Cohen M . The role of sexually transmitted diseases in HIV transmission. Nat Rev Microbiol. 2004; 2(1):33-42. DOI: 10.1038/nrmicro794. View

Ham A, Ugaonkar S, Shi L, Watson Buckheit K, Lakougna H, Nagaraja U . Development of a combination microbicide gel formulation containing IQP-0528 and tenofovir for the prevention of HIV infection. J Pharm Sci. 2012; 101(4):1423-35. DOI: 10.1002/jps.23026. View

Agrahari V, Putty S, Mathes C, Murowchick J, Youan B . Evaluation of degradation kinetics and physicochemical stability of tenofovir. Drug Test Anal. 2014; 7(3):207-13. PMC: 4278957. DOI: 10.1002/dta.1656. View

PLATT E, Wehrly K, Kuhmann S, Chesebro B, Kabat D . Effects of CCR5 and CD4 cell surface concentrations on infections by macrophagetropic isolates of human immunodeficiency virus type 1. J Virol. 1998; 72(4):2855-64. PMC: 109730. DOI: 10.1128/JVI.72.4.2855-2864.1998. View

Fichorova R, Tucker L, Anderson D . The molecular basis of nonoxynol-9-induced vaginal inflammation and its possible relevance to human immunodeficiency virus type 1 transmission. J Infect Dis. 2001; 184(4):418-28. DOI: 10.1086/322047. View

Thigpen M, Kebaabetswe P, Paxton L, Smith D, Rose C, Segolodi T . Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012; 367(5):423-34. DOI: 10.1056/NEJMoa1110711. View

Baeten J, Donnell D, Ndase P, Mugo N, Campbell J, Wangisi J . Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012; 367(5):399-410. PMC: 3770474. DOI: 10.1056/NEJMoa1108524. View

Abdool Karim Q, Abdool Karim S, Frohlich J, Grobler A, Baxter C, Mansoor L . Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010; 329(5996):1168-74. PMC: 3001187. DOI: 10.1126/science.1193748. View

Grooms T, Vuong H, Tyo K, Malik D, Sims L, Whittington C . Griffithsin-Modified Electrospun Fibers as a Delivery Scaffold To Prevent HIV Infection. Antimicrob Agents Chemother. 2016; 60(11):6518-6531. PMC: 5075055. DOI: 10.1128/AAC.00956-16. View

10.

Owen D, Katz D . A vaginal fluid simulant. Contraception. 1999; 59(2):91-5. DOI: 10.1016/s0010-7824(99)00010-4. View

11.

Ball C, Krogstad E, Chaowanachan T, Woodrow K . Drug-eluting fibers for HIV-1 inhibition and contraception. PLoS One. 2012; 7(11):e49792. PMC: 3509119. DOI: 10.1371/journal.pone.0049792. View

12.

Huang C, Soenen S, Van Gulck E, Vanham G, Rejman J, Van Calenbergh S . Electrospun cellulose acetate phthalate fibers for semen induced anti-HIV vaginal drug delivery. Biomaterials. 2011; 33(3):962-9. DOI: 10.1016/j.biomaterials.2011.10.004. View

13.

Nel A, Smythe S, Young K, Malcolm K, McCoy C, Rosenberg Z . Safety and pharmacokinetics of dapivirine delivery from matrix and reservoir intravaginal rings to HIV-negative women. J Acquir Immune Defic Syndr. 2009; 51(4):416-23. DOI: 10.1097/qai.0b013e3181acb536. View

14.

Fichorova R, Mendonca K, Yamamoto H, Murray R, Chandra N, Doncel G . A quantitative multiplex nuclease protection assay reveals immunotoxicity gene expression profiles in the rabbit model for vaginal drug safety evaluation. Toxicol Appl Pharmacol. 2015; 285(3):198-206. DOI: 10.1016/j.taap.2015.02.017. View

15.

Beyrer C, Baral S, van Griensven F, Goodreau S, Chariyalertsak S, Wirtz A . Global epidemiology of HIV infection in men who have sex with men. Lancet. 2012; 380(9839):367-77. PMC: 3805037. DOI: 10.1016/S0140-6736(12)60821-6. View

16.

Doncel G, Chandra N, Fichorova R . Preclinical assessment of the proinflammatory potential of microbicide candidates. J Acquir Immune Defic Syndr. 2006; 37 Suppl 3:S174-80. View

17.

Blakney A, Krogstad E, Jiang Y, Woodrow K . Delivery of multipurpose prevention drug combinations from electrospun nanofibers using composite microarchitectures. Int J Nanomedicine. 2014; 9:2967-78. PMC: 4069153. DOI: 10.2147/IJN.S61664. View

18.

Asvadi N, Dang N, Davis-Poynter N, Coombes A . Evaluation of microporous polycaprolactone matrices for controlled delivery of antiviral microbicides to the female genital tract. J Mater Sci Mater Med. 2013; 24(12):2719-27. DOI: 10.1007/s10856-013-5010-6. View

19.

Chew S, Hufnagel T, Lim C, Leong K . Mechanical properties of single electrospun drug-encapsulated nanofibres. Nanotechnology. 2011; 17(15):3880-3891. PMC: 2597803. DOI: 10.1088/0957-4484/17/15/045. View

20.

Dayal M, Wheeler J, Williams C, Barnhart K . Disruption of the upper female reproductive tract epithelium by nonoxynol-9. Contraception. 2003; 68(4):273-9. DOI: 10.1016/s0010-7824(03)00178-1. View