Acta Scientific Pharmaceutical Sciences (ASPS)(ISSN: 2581-5423)

Research Article Volume 7 Issue 2

Evaluation of Topical Microbicides for their Acute Toxicities and Ability to Induce Proinflammatory Cytokines TNF-a, IL-1b, IL-6 and IL-8 in Peripheral Blood Mononuclear Cells and Macrophages

Aladin A Siddig1, Olivier M Tchimou1, Mohammad N Uddin2 and Kwame G Yeboah3*

1University of Charleston School of Pharmacy, Charleston, West Virginia, USA
2Mercer University College of Pharmacy and Health Sciences, Atlanta, Georgia, USA
3Harding University College of Pharmacy, Search, Arkansas, USA

*Corresponding Author: Kwame G Yeboah, Harding University College of Pharmacy, Search, Arkansas, USA.

Received: November 22, 2022; Published: January 10, 2022

Abstract

Purpose: Topical Microbicides have been used as vaginal microbicides in clinical trials as anti-HIV-1 products. The objectives of this project were to evaluate selected popular topical microbicide drug products for their acute toxicities to colorectal epithelial cells and primary immune cells such as Peripheral Blood Mononuclear Cells (PBMC) and Macrophages and to further determine if these microbicide products could induce genital tract inflammation via extra production of pro-inflammatory cytokines such as TNF-a, IL-1b, IL-6 and IL-8.

Methodology: Toxicities of Nonoxynol-9, KY jelly, CAP, PRO2000 (4%), PRO2000 (0.5%), UC781(1%), UC781(0.1%) and VenaGelTM microbicides were determined by cellular viability of colorectal adenocarcinoma cells (CaCo2), the model vaginal epithelial cell and the vaginal tract primary immune cells of peripheral blood mononuclear cells (PBMCs) and Macrophages by culturing them for 24-hours in the presence of serial dilutions of products or placebo. Products and placebo dilutions that gave culture viabilities of ≥60% compared to control cultures were considered as nontoxic

Results: The results indicated safety and low toxicity of these microbicides in terms of cytokine release. Furthermore, it showed that usage of these microbicides as anti-HIV formulation will not trigger cytokine release. However, IL-8 has shown relatively higher levels for all microbicides tested in toxic and nontoxic formulation. This indicated that microbicides induced the release of IL-8 and could trigger the recruitment of HIV-1 susceptible cells and increase HIV-1 replication.

Keywords: Nonoxynol-9; KY Jelly; CAP; Cytokines; TNF-a; IL-1b; IL-6 and IL-8

References

  1. UNAIDS Data (2021).
  2. Hladik F and Doncel, GF. “Preventing mucosal HIV transmission with topical microbicides: Challenges and opportunities”. Antiviral Research 88S (2010): 53-59.
  3. Tesoriero JM., et al. “COVID-19 outcomes among persons living with or without diagnosed HIV infection in New York State”. JAMA Network Open2 (2021).
  4. Dezzutti CS., et al. “In vitro Comparison of Tropical Microbicides for Prevention of Human Immunodeficiency Virus Type 1 Transmission”. Antimicrobial Agents and Chemotherapy 48.10 (2004): 3834-3844.
  5. Baeten JM., et al. “Topical Microbicides in HIV Prevention: State of the Promise”. Annual Review of Medicine71 (2020): 361-377.
  6. Stone A. “Microbicides: A new approach to preventing HIV and other sexually transmitted infections”. Nature Reviews 1 (2002): 977-985.
  7. Turpin JA. “Consideration and development of topical microbicides to inhibit the sexual transmission of HIV”. Expert Opinion on Investigational Drugs8 (2005): 1077-1097.
  8. Singh O., et al. “Microbicides for the treatment of sexually transmitted HIV infections”. Journal of Pharmaceutics (Cairo) (2014): 352425.
  9. Doncel GF and Clark MR. “Preclinical evaluation of anti-HIV microbicide products: New models and biomarkers”. Antiviral Research 88S (2010): S10-S18.
  10. Taha TE., et al. “Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV”. AIDS 12 (1998): 1699-1706.
  11. Marziano M., et al. “Monitoring CaCo-2 to enterocyte-like cells differentiation by means of electric impedance analysis on printed sensors”. Biochimica Biophysica Acta-General Subjects 1863.5 (2019): 893-902.
  12. Maguire RA., et al. “Comparison of microbicides for efficacy in protecting mice against vaginal challenge and herpes simplex virus type 2, cytotoxicity, antibacterial properties, and sperm immobilization”. Sexually Transmitted Diseases 28 (2001): 259-265.
  13. Kelly CG and Shattock RJ. “Specific microbicides in the prevention of HIV infection”. Journal of Internal Medicine 6 (2011): 509-519.
  14. Abdool Karim SS and Baxter C. “Overview of microbicides for the prevention of human immunodeficiency virus”. Best Practice and Research Clinical Obstetrics and Gynaecology4 (2012): 427-439.
  15. Fogh J., et al. “Absence of HeLa cell contamination in 169 cell lines derived from human tumors”. Journal of National Cancer Institute 58 (1977): 209-214.
  16. Belec F., et al. “Proinflammatory cytoking expression in cervicovaginal secretions of normal and HIV-infected women”. Cytokine 7.6 (1995): 568-574.
  17. Lushbaugh WB., et al. “Use of intravaginal microbicides to prevent acquisition of Trichomonas vaginalis infection in Lactobacilus-penetrated, estrogenized young mice”. American Journal of Tropical Medicine and Hygiene 63 (2000): 284-289.
  18. Nutan and Gupta SK. “Microbicide: a new hope for HIV prevention”. Indian Journal of Medical Research6 (2011): 939-949.
  19. Bourinbaiar AS and Fruhstorfer EC. “The efficacy of nonoxymol-9 from and in vitro point of view”. AIDS 10 (1996): 558-559.
  20. Zacharopoulos VR and Phillips DM. “Vaginal formulations of carrageen protect mice from herpes simplex virus infection”. Clinical and Diagnostic Laboratory Immunology 4 (1997): 465-468.
  21. Sullivan PS., et al. “Human immunodeficiency virus (HIV) subtype surveillance of African-born persons at risk for group O and group N HIV infections in the United States”. The Journal of Infectious Diseases 2 (2000): 463-469.
  22. Niruthisard S., et al. “The effects of frequent nonoxynol-9 use on the vaginal and cervical mucosa”. Sexually Transmitted Diseases3 (1991): 176-179.
  23. Stafford MK., et al. “Safety study of Nonoxynol-9 as a vaginal microbicide: Evidence of adverse effects”. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology4 (1998): 327-331.
  24. Mayer KH., et al. “Safety and tolerability of vaginal PRO 2000 gel in sexually active HIV-uninfected and abstinent HIV-infected women”. AIDS 17 (2021): 321-329.
  25. Hladik F., et al. “Dendritic cell-T-cell interactions support coreceptor-independent human immunodeficiency virus type-1 transmission in the human genital tract”. Journal of Virology 73 (1999): 5833-5842.
  26. Neurath AR., et al. “Anti-HIV-1 activity of cellulose phthalate: Synergy with soluble CD4 and induction of “dead-end” gp41 six-helix bundles”. BMC Infectious Diseases 2 (2002): 6.
  27. Zeitlin L., et al. “Tests of Buffergel for contraception and prevention of sexually transmitted diseases in animal models”. Sexually Transmitted Diseases 28 (2001): 417-423.
  28. Fichorova RN., et al. “Anti-human immunodeficiency virus type 1 microbicide cellulose acetate 1,2-bezendicarboxylate in a human in vitro model of vaginal inflammation”. Antimicrobial Agents and Chemotherapy1 (2005): 323-335.
  29. Fichorova RN., et al. “The molecular basis of nomoxynol-9-induced vaginal inflammation and its possible relevance to human immunodeficiency virus type transmission”. Journal of Infectious Diseases4 (2001): 418-428.
  30. Ayehunie S., et al. “Organotypic human vaginal-ectocervical tissue model for irrigation irritation studies of spermicides, microbicides, and feminine-care products”. Toxicology in Vitro 20 (2006): 689-698.
  31. Neurath AR., et al. “Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120”. BMC Infectious Diseases 1 (2001): 17.
  32. Skoler-Karpoff S., et al. “Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomized, double-blind, placebo-controlled trial”. The Lancet9654 (2008): 1977-1987.
  33. Roberts L., et al. “Genital tract inflammation during early HIV-1 infection predicts higher plasma viral load set point in women”. The Journal of Infectious Disease2 (2012): 194-203.

Citation

Citation: Kwame G Yeboah., et al. “Evaluation of Topical Microbicides for their Acute Toxicities and Ability to Induce Proinflammatory Cytokines TNF-a, IL-1b, IL-6 and IL-8 in Peripheral Blood Mononuclear Cells and Macrophages". Acta Scientific Pharmaceutical Sciences 7.2 (2023): 23-36.

Copyright

Copyright: © 2022 Kwame G Yeboah., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.




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