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Thermosensitive and mucoadhesive pluronic-hydroxypropylmethylcellulose hydrogel containing the mini-CD4 M48U1 is a promising efficient barrier against HIV diffusion through macaque cervicovaginal mucus.

Abstract
To be efficient, vaginal microbicide hydrogels should form a barrier against viral infections and prevent virus spreading through mucus. Multiple particle tracking was used to quantify the mobility of 170-nm fluorescently labeled COOH-modified polystyrene particles (COOH-PS) into thermosensitive hydrogels composed of amphiphilic triblock copolymers with block compositions EOn-POm-EOn (where EO refers to ethylene oxide and PO to propylene oxide) containing mucoadhesive hydroxypropylmethylcellulose (HPMC). COOH-PS were used to mimic the size and the surface charge of HIV-1. Analysis of COOH-PS trajectories showed that particle mobility was decreased by Pluronic hydrogels in comparison with cynomolgus macaque cervicovaginal mucus and hydroxyethylcellulose hydrogel (HEC; 1.5% by weight [wt%]) used as negative controls. Formulation of the peptide mini-CD4 M48U1 used as an anti-HIV-1 molecule into a mixture of Pluronic F127 (20 wt%) and HPMC (1 wt%) did not affect its anti-HIV-1 activity in comparison with HEC hydrogel. The 50% inhibitory concentration (IC50) was 0.53 μg/ml (0.17 μM) for M48U1-HEC and 0.58 μg/ml (0.19 μM) for M48U1-F127-HPMC. The present work suggests that hydrogels composed of F127-HPMC (20/1 wt%, respectively) can be used to create an efficient barrier against particle diffusion in comparison to conventional HEC hydrogels.
AuthorsKawthar Bouchemal, Armelle Aka-Any-Grah, Nathalie Dereuddre-Bosquet, Loïc Martin, Vanessa Lievin-Le-Moal, Roger Le Grand, Valérie Nicolas, Davide Gibellini, David Lembo, Christian Poüs, Armand Koffi, Gilles Ponchel
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 59 Issue 4 Pg. 2215-22 (Apr 2015) ISSN: 1098-6596 [Electronic] United States
PMID25645853 (Publication Type: Journal Article)
CopyrightCopyright © 2015, American Society for Microbiology. All Rights Reserved.
Chemical References
  • Anti-HIV Agents
  • CD4 Antigens
  • Fluorescent Dyes
  • HIV Fusion Inhibitors
  • Hydrogels
  • PEO-PPO-PEO
  • Propylene Glycols
  • Poloxamer
  • Hypromellose Derivatives
  • Polyethylene Glycols
Topics
  • Animals
  • Anti-HIV Agents (chemical synthesis, pharmacology)
  • CD4 Antigens (chemistry, pharmacology)
  • Cervix Mucus (drug effects, virology)
  • Diffusion
  • Female
  • Fluorescent Dyes
  • HIV Fusion Inhibitors (chemical synthesis, pharmacology)
  • HIV Infections (prevention & control, virology)
  • HIV-1 (drug effects)
  • Humans
  • Hydrogels (chemical synthesis, chemistry, pharmacology)
  • Hypromellose Derivatives (chemical synthesis, chemistry, pharmacology)
  • Macaca fascicularis
  • Poloxamer (chemistry, pharmacology)
  • Polyethylene Glycols (chemistry, pharmacology)
  • Propylene Glycols (chemistry, pharmacology)
  • Rheology
  • Viscosity

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