title: 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.
authors: Université Paris-Sud, Institut Galien Paris Sud, UMR CNRS 8612, Faculté de Pharmacie, Châtenay-Malabry, France kawthar.bouchemal@u-psud.fr.
authors: Kawthar
authors: K
authors: Bouchemal
authors: Université Paris-Sud, Institut Galien Paris Sud, UMR CNRS 8612, Faculté de Pharmacie, Châtenay-Malabry, France Université Félix Houphouet Boigny-Cocody, UFR des Sciences Pharmaceutiques et Biologiques, Laboratoire de Pharmacie Galénique, Biopharmacie et Législation, Abidjan, Côte d'Ivoire.
authors: Armelle
authors: A
authors: Aka-Any-Grah
authors: CEA, iMETI, Division of Immuno-Virology, Fontenay-aux Roses, France.
authors: Nathalie
authors: N
authors: Dereuddre-Bosquet
authors: CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Gif sur Yvette, France.
authors: Loïc
authors: L
authors: Martin
authors: Antiparasitic Chemotherapy, UMR CNRS 8076, Faculté de Pharmacie, Châtenay-Malabry, France.
authors: Vanessa
authors: V
authors: Lievin-Le-Moal
authors: CEA, iMETI, Division of Immuno-Virology, Fontenay-aux Roses, France.
authors: Roger
authors: R
authors: Le Grand
authors: Université Paris-Sud, IFR 141, Faculté de Pharmacie, Châtenay-Malabry, France.
authors: Valérie
authors: V
authors: Nicolas
authors: Department of Pathology and Diagnostic, Microbiology and Virology Unit, University of Verona, Verona, Italy.
authors: Davide
authors: D
authors: Gibellini
authors: University of Turin, Department of Clinical and Biological Sciences, S. Luigi Gonzaga Hospital Regione Gonzole, Orbassano, Turin, Italy.
authors: David
authors: D
authors: Lembo
authors: Biochimie et Biologie Cellulaire-JE2493, Université Paris-Sud, IFR 141, Faculté de Pharmacie, Châtenay-Malabry, France.
authors: Christian
authors: C
authors: Poüs
authors: Université Félix Houphouet Boigny-Cocody, UFR des Sciences Pharmaceutiques et Biologiques, Laboratoire de Pharmacie Galénique, Biopharmacie et Législation, Abidjan, Côte d'Ivoire.
authors: Armand
authors: A
authors: Koffi
authors: Université Paris-Sud, Institut Galien Paris Sud, UMR CNRS 8612, Faculté de Pharmacie, Châtenay-Malabry, France.
authors: Gilles
authors: G
authors: Ponchel
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015704:CD4 Antigens / Q000737:chemistry* / Q000494:pharmacology*; D002582:Cervix Mucus / Q000187:drug effects* / Q000821:virology*; D004058:Diffusion; D005260:Female; D005456:Fluorescent Dyes; D023581:HIV Fusion Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015658:HIV Infections / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D065347:Hypromellose Derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008252:Macaca fascicularis; D020442:Poloxamer / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D011409:Propylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D012212:Rheology; D014783:Viscosity
chemical_list: D019380:Anti-HIV Agents; D015704:CD4 Antigens; D005456:Fluorescent Dyes; D023581:HIV Fusion Inhibitors; D020100:Hydrogels; C116176:PEO-PPO-PEO; D011409:Propylene Glycols; D020442:Poloxamer; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols
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