title: In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate.
abstract: BACKGROUND
  Copper has antimicrobial properties and has been studied for its activity against viruses, including HIV. Copper complexed within a phthalocyanine ring, forming copper (II) phthalocyanine sulfate (CuPcS), may have a role in microbicide development when used intravaginally.
  
  
  METHODS
  CuPcS toxicity was tested against cervical epithelial cells, TZM-BL cells, peripheral blood mononuclear cells (PBMC), and cervical explant tissues using cell viability assays. In vivo toxicity was assessed following intravaginal administration of CuPcS in female BALB/C mice and measured using a standardized histology grading system on reproductive tract tissues. Efficacy studies for preventing infection with HIV in the presence of various non-toxic concentrations of CuPcS were carried out in TZM-BL, PBMC, and cervical explant cultures using HIV-1BAL and various pseudovirus subtypes. Non-linear regression was applied to the data to determine the EC50/90 and CC50/90.
  
  
  RESULTS
  CuPcS demonstrated inhibition of HIV infection in PBMCs at concentrations that were non-toxic in cervical epithelial cells and PBMCs with EC50 values of approximately 50 μg/mL. Reproductive tract tissue analysis revealed no toxicity at 100 mg/mL. Human cervical explant tissues challenged with HIV in the presence of CuPcS also revealed a dose-response effect at preventing HIV infection at non-toxic concentrations with an EC50 value of 65 μg/mL.
  
  
  CONCLUSIONS
  These results suggest that CuPcS may be useful as a topical microbicide in concentrations that can be achieved in the female genital tract.
authors: Department of Infectious Disease, University of Illinois at Chicago, Chicago, IL, 60612, USA. Ashley.styczynski@gmail.com.|Department of Internal Medicine, George Washington University, Washington, DC, 20037, USA. Ashley.styczynski@gmail.com.|, 755 North Ave NE #1319, Atlanta, GA, 30306, USA. Ashley.styczynski@gmail.com.
authors: Ashley R
authors: AR
authors: Styczynski
authors: Department of Infectious Disease, University of Illinois at Chicago, Chicago, IL, 60612, USA. kanwar@uic.edu.
authors: Khandaker N
authors: KN
authors: Anwar
authors: Department of Infectious Disease, University of Illinois at Chicago, Chicago, IL, 60612, USA. sultanah@uic.edu.
authors: Habiba
authors: H
authors: Sultana
authors: Department of Infectious Disease, University of Illinois at Chicago, Chicago, IL, 60612, USA. aghanem@uic.edu.
authors: Abdelhamid
authors: A
authors: Ghanem
authors: Department of Infectious Disease, Rush University, Chicago, IL, 60612, USA. Nell_Lurain@rush.edu.
authors: Nell
authors: N
authors: Lurain
authors: Department of Infectious Disease, University of Illinois at Chicago, Chicago, IL, 60612, USA. jchua3@uic.edu.
authors: Aishi
authors: A
authors: Chua
authors: Department of Infectious Disease, University of Illinois at Chicago, Chicago, IL, 60612, USA. ghassemi@uic.edu.
authors: Mahmood
authors: M
authors: Ghassemi
authors: Department of Infectious Disease, University of Illinois at Chicago, Chicago, IL, 60612, USA. rmnovak@uic.edu.
authors: Richard M
authors: RM
authors: Novak
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000009:adverse effects / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009942:Organometallic Compounds / Q000009:adverse effects / Q000494:pharmacology*; D013431:Sulfates / Q000009:adverse effects / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D000891:Anti-Infective Agents, Local; D007211:Indoles; D009942:Organometallic Compounds; D013431:Sulfates; C015445:copper phthalocyanine