Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine

J. das Neves, J. Michiels, K.K. Ariën, G. Vanham, M. Amiji, M.F. Bahia, B. Sarmento

Research output: Contribution to journalA1: Web of Science-article

Abstract

PURPOSE: To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(epsilon-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.
Original languageEnglish
JournalPharmaceutical Research
Volume29
Issue number6
Pages (from-to)1468-1484
Number of pages17
ISSN0724-8741
DOIs
Publication statusPublished - 2012

Keywords

  • Viral diseases
  • HIV
  • AIDS
  • Drug development
  • Microbicides
  • HAART
  • Antiretrovirals
  • Drug activity
  • Dapivirine
  • Assessment
  • Intracellular
  • Cytotoxicity
  • Nanoparticles

Fingerprint

Dive into the research topics of 'Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine'. Together they form a unique fingerprint.

Cite this