title: Chitosan and Kappa-Carrageenan Vaginal Acyclovir Formulations for Prevention of Genital Herpes. In Vitro and Ex Vivo Evaluation.
abstract: Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Polysaccharides, such as chitosan and carrageenan, which have good binding capacity with mucosal tissues, are now included in vaginal delivery systems. Marine polymer-based vaginal mucoadhesive solid formulations have been developed for the controlled release of acyclovir, which may prevent the sexual transmission of the herpes simplex virus. Drug release studies were carried out in two media: simulated vaginal fluid and simulated vaginal fluid/simulated seminal fluid mixture. The bioadhesive capacity and permanence time of the bioadhesion, the prepared compacts, and compacted granules were determined ex vivo using bovine vaginal mucosa as substrate. Swelling processes were quantified to confirm the release data. Biocompatibility was evaluated through in vitro cellular toxicity assays, and the results showed that acyclovir and the rest of the materials had no cytotoxicity at the maximum concentration tested. The mixture of hydroxyl-propyl-methyl-cellulose with chitosan- or kappa-carrageenan-originated mucoadhesive systems that presented a complete and sustained release of acyclovir for a period of 8-9 days in both media. Swelling data revealed the formation of optimal mixed chitosan/hydroxyl-propyl-methyl-cellulose gels which could be appropriated for the prevention of sexual transmission of HSV.
authors.affiliation: Departamento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid, Spain. mdelpilarss@gmail.com.
authors.forename: María-Pilar
authors.initials: MP
authors.lastname: Sánchez-Sánchez
authors.affiliation: Departamento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid, Spain. aracelimartin@ucm.es.
authors.forename: Araceli
authors.initials: A
authors.lastname: Martín-Illana
authors.affiliation: Departamento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid, Spain. rruizcar@ucm.es.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ruiz-Caro
authors.affiliation: Departamento Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid, Spain. naber@ucm.es.
authors.forename: Paulina
authors.initials: P
authors.lastname: Bermejo
authors.affiliation: Departamento Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid, Spain. mjabad@farm.ucm.es.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Abad
authors.affiliation: Departamento Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid, Spain. rubencarrohernan@gmail.com.
authors.forename: Rubén
authors.initials: R
authors.lastname: Carro
authors.affiliation: Departamento Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid, Spain. lmbedoya@ucm.es.
authors.forename: Luis-Miguel
authors.initials: LM
authors.lastname: Bedoya
authors.affiliation: Instituto de Cerámica y Vidrio, Consejo Superior de Investigaciones Científicas, 28049-Madrid, Spain,. aitanath@icv.csic.es.
authors.forename: Aitana
authors.initials: A
authors.lastname: Tamayo
authors.affiliation: Instituto de Cerámica y Vidrio, Consejo Superior de Investigaciones Científicas, 28049-Madrid, Spain,. jrubio@icv.csic.es.
authors.forename: Juan
authors.initials: J
authors.lastname: Rubio
authors.affiliation: Departamento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Vida s/n, 15782 Santiago de Compostela, Spain. anxordes@gmail.com.
authors.forename: Anxo
authors.initials: A
authors.lastname: Fernández-Ferreiro
authors.affiliation: Departamento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Vida s/n, 15782 Santiago de Compostela, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Otero-Espinar
authors.affiliation: Departamento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid, Spain. mdveiga@ucm.es.
authors.forename: María-Dolores
authors.initials: MD
authors.lastname: Veiga
mesh_terms: D000212:Acyclovir / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D006558:Herpes Genitalis / Q000188:drug therapy*; D006801:Humans
chemical_list: D002351:Carrageenan; D048271:Chitosan; D000212:Acyclovir
keywords: acyclovir controlled release; chitosan; cytotoxicity; ex vivo bioadhesion; genital herpes; kappa-carrageenan; swelling behaviour; vaginal mucoadhesive formulations