PMID- 25700657
OWN - NLM
STAT- MEDLINE
DCOM- 20160111
LR  - 20220408
IS  - 1878-7568 (Electronic)
IS  - 1742-7061 (Linking)
VI  - 18
DP  - 2015 May
TI  - Precise engineering of dapivirine-loaded nanoparticles for the development of 
      anti-HIV vaginal microbicides.
PG  - 77-87
LID - S1742-7061(15)00070-7 [pii]
LID - 10.1016/j.actbio.2015.02.007 [doi]
AB  - Polymeric nanoparticles (NPs) have the potential to provide effective and safe 
      delivery of antiretroviral drugs in the context of prophylactic anti-HIV vaginal 
      microbicides. Dapivirine-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) NPs were 
      produced by an emulsion-solvent evaporation method, optimized for colloidal 
      properties using a 3-factor, 3-level Box-Behnken experimental design, and 
      characterized for drug loading, production yield, morphology, thermal behavior, 
      drug release, in vitro cellular uptake, cytotoxicity and pro-inflammatory 
      potential. Also, drug permeability/membrane retention in well-established HEC-1-A 
      and CaSki cell monolayer models as mediated by NPs was assessed in the absence or 
      presence of mucin. Box-Behnken design allowed optimizing monodisperse 170nm 
      drug-loaded NPs. Drug release experiments showed an initial burst effect up to 
      4h, followed by sustained 24h release at pH 4.2 and 7.4. NPs were readily taken 
      up by different genital and macrophage cell lines as assessed by fluorescence 
      microscopy. Drug-loaded NPs presented lower or at least similar cytotoxicity as 
      compared to the free drug, with up to around one-log increase in half-maximal 
      cytotoxic concentration values. In all cases, no relevant changes in cell 
      pro-inflammatory cytokine/chemokine production were observed. Dapivirine 
      transport across cell monolayers was significantly decreased when mucin was 
      present at the donor side with either NPs or the free drug, thus evidencing the 
      influence of this natural glycoprotein in membrane permeability. Moreover, drug 
      retention in cell monolayers was significantly higher for NPs in comparison with 
      the free drug. Overall, obtained dapivirine-loaded PLGA NPs possess interesting 
      technological and biological features that may contribute to their use as novel 
      safe and effective vaginal microbicides.
CI  - Copyright (c) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights 
      reserved.
FAU - das Neves, Jose
AU  - das Neves J
AD  - INEB - Instituto de Engenharia Biomedica, Universidade do Porto, Porto, Portugal; 
      CESPU, Instituto de Investigacao e Formacao Avancada em Ciencias e Tecnologias da 
      Saude, Gandra PRD, Portugal; Instituto de Investigacao e Inovacao em Saude, 
      Universidade do Porto, Portugal. Electronic address: j.dasneves@ineb.up.pt.
FAU - Sarmento, Bruno
AU  - Sarmento B
AD  - INEB - Instituto de Engenharia Biomedica, Universidade do Porto, Porto, Portugal; 
      CESPU, Instituto de Investigacao e Formacao Avancada em Ciencias e Tecnologias da 
      Saude, Gandra PRD, Portugal; Instituto de Investigacao e Inovacao em Saude, 
      Universidade do Porto, Portugal.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150217
PL  - England
TA  - Acta Biomater
JT  - Acta biomaterialia
JID - 101233144
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Anti-Infective Agents)
RN  - 0 (Chemokines)
RN  - 0 (Pyrimidines)
RN  - TCN4MG2VXS (Dapivirine)
SB  - IM
MH  - Animals
MH  - Anti-HIV Agents/chemistry/*pharmacology
MH  - Anti-Infective Agents/chemistry/*pharmacology
MH  - Cell Death/drug effects
MH  - Cell Membrane Permeability/drug effects
MH  - Cell Survival/drug effects
MH  - Chemokines/metabolism
MH  - Drug Liberation
MH  - Endocytosis/drug effects
MH  - Female
MH  - HeLa Cells
MH  - Humans
MH  - Hydrodynamics
MH  - Inflammation/pathology
MH  - Mice
MH  - Nanoparticles/*chemistry
MH  - Nanotechnology/*methods
MH  - Particle Size
MH  - Pyrimidines/*pharmacology
MH  - RAW 264.7 Cells
MH  - Temperature
MH  - Vagina/*drug effects
OTO - NOTNLM
OT  - Cytotoxicity
OT  - Mucin
OT  - Poly(d,l-lactic-co-glycolic acid)
OT  - Response surface methodology
OT  - Vaginal drug delivery
EDAT- 2015/02/24 06:00
MHDA- 2016/01/12 06:00
CRDT- 2015/02/22 06:00
PHST- 2014/10/23 00:00 [received]
PHST- 2014/12/27 00:00 [revised]
PHST- 2015/02/10 00:00 [accepted]
PHST- 2015/02/22 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2016/01/12 06:00 [medline]
AID - S1742-7061(15)00070-7 [pii]
AID - 10.1016/j.actbio.2015.02.007 [doi]
PST - ppublish
SO  - Acta Biomater. 2015 May;18:77-87. doi: 10.1016/j.actbio.2015.02.007. Epub 2015 
      Feb 17.