pH-Dependent Molecular Gate Mesoporous Microparticles for Biological Control of <i>Giardia intestinalis</i>
Isabel González-Alvarez,
Verónica Vivancos,
Carmen Coll,
Bárbara Sánchez-Dengra,
Elena Aznar,
Alejandro Ruiz-Picazo,
Marival Bermejo,
Félix Sancenón,
María Auxiliadora Dea-Ayuela,
Marta Gonzalez-Alvarez,
Ramón Martínez-Máñez
Affiliations
Isabel González-Alvarez
Department of Engineering, Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, Elche. San Juan Campus, 03550 San Juan, Spain
Verónica Vivancos
Department of Engineering, Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, Elche. San Juan Campus, 03550 San Juan, Spain
Carmen Coll
Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico, Universitat Politècnica de València and Universitat de València, Camino de Vera s/n, 46022 Valencia, Spain
Bárbara Sánchez-Dengra
Department of Engineering, Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, Elche. San Juan Campus, 03550 San Juan, Spain
Elena Aznar
Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico, Universitat Politècnica de València and Universitat de València, Camino de Vera s/n, 46022 Valencia, Spain
Alejandro Ruiz-Picazo
Department of Engineering, Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, Elche. San Juan Campus, 03550 San Juan, Spain
Marival Bermejo
Department of Engineering, Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, Elche. San Juan Campus, 03550 San Juan, Spain
Félix Sancenón
Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico, Universitat Politècnica de València and Universitat de València, Camino de Vera s/n, 46022 Valencia, Spain
María Auxiliadora Dea-Ayuela
Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, C/Santiago Ramón y Cajal, s/n, Alfara del Patriarca, 46115 Valencia, Spain
Marta Gonzalez-Alvarez
Department of Engineering, Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, Elche. San Juan Campus, 03550 San Juan, Spain
Ramón Martínez-Máñez
Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico, Universitat Politècnica de València and Universitat de València, Camino de Vera s/n, 46022 Valencia, Spain
Giardiasis is a parasitism produced by the protozoa Giardia intestinalis that lives as trophozoite in the small intestine (mainly in the duodenum) attached to the intestinal villus by means of billed discs. The first line treatment is metronidazole, a drug with high bioavailability, which is why to obtain therapeutic concentrations in duodenum, it is necessary to administer high doses of drug to patients with the consequent occurrence of side effects. It is necessary to developed new therapeutical approaches to achieve a local delivery of the drug. In this sense, we have developed gated mesoporous silica microparticles loaded with metronidazole and with a molecular gate pH dependent. In vitro assays demonstrated that the metronidazole release is practically insignificant at acidic pHs, but in duodenum conditions, the metronidazole delivery from the microparticles is effective enough to produce an important parasite destruction. In vivo assays indicate that this microparticulate system allows to increase the concentration of the drug in duodenum and reduce the concentration in plasma avoiding systemic effects. This system could be useful for other intestinal local treatments in order to reduce doses and increase drug availability in target tissues.