NDLI: Polymeric Nanoparticles Affect the Intracellular Delivery, Antiretroviral Activity and Cytotoxicity of the Microbicide Drug Candidate Dapivirine

Content Provider	Springer Nature Link
Author	das Neves, José Michiels, Johan Ariën, Kevin K. Vanham, Guido Amiji, Mansoor Bahia, Maria Fernanda Sarmento, Bru
Copyright Year	2011
Abstract	To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(ε-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine.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.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.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.
Starting Page	1468
Ending Page	1484
Page Count	17
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	29
Issue Number	6
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2011-11-10
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacy Medical Law Pharmacology/Toxicology Biomedical Engineering Biochemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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