title: Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine.
abstract: OBJECTIVE
  To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(ε-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine.
  
  
  METHODS
  Dapivirine-loaded nanoparticles with different surface properties were produced using three surface modifiers: poloxamer 338 NF (PEO), sodium lauryl sulfate (SLS) and cetyl trimethylammonium bromide (CTAB). The ability of nanoparticles to promote intracellular drug delivery was assessed in different cell types relevant for vaginal HIV transmission/microbicide development. Also, antiretroviral activity of nanoparticles was determined in different cell models, as well as their cytotoxicity.
  
  
  RESULTS
  Dapivirine-loaded nanoparticles were readily taken up by different cells, with particular kinetics depending on the cell type and nanoparticles, resulting in enhanced intracellular drug delivery in phagocytic cells. Different nanoparticles showed similar or improved antiviral activity compared to free drug. There was a correlation between increased antiviral activity and increased intracellular drug delivery, particularly when cell models were submitted to a single initial short-course treatment. PEO-PCL and SLS-PCL nanoparticles consistently showed higher selectivity index values than free drug, contrasting with high cytotoxicity of CTAB-PCL.
  
  
  CONCLUSIONS
  These results provide evidence on the potential of PCL nanoparticles to affect in vitro toxicity and activity of dapivirine, depending on surface engineering. Thus, this formulation approach may be a promising strategy for the development of next generation microbicides.
authors.affiliation: Laboratory of Pharmaceutical Technology, LTF/CICF Faculty of Pharmacy, University of Porto, Rua Aníbal Cunha, 164, 4050-047, Porto, Portugal. j.dasneves@gmail.com
authors.forename: José
authors.initials: J
authors.lastname: das Neves
authors.forename: Johan
authors.initials: J
authors.lastname: Michiels
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Ariën
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
authors.forename: Mansoor
authors.initials: M
authors.lastname: Amiji
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Bahia
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001692:Biological Transport; D018938:Caco-2 Cells; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D005260:Female; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D051379:Mice; D053758:Nanoparticles; D036103:Nanotechnology; D020442:Poloxamer / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry* / Q000633:toxicity; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D019380:Anti-HIV Agents; D002593:Cetrimonium Compounds; D004337:Drug Carriers; D011091:Polyesters; D011743:Pyrimidines; D013501:Surface-Active Agents; D020442:Poloxamer; C016240:polycaprolactone; D012967:Sodium Dodecyl Sulfate; C481671:Dapivirine; D000077286:Cetrimonium
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