pH-Dependent Molecular Gate Mesoporous Microparticles for Biological Control of Giardia intestinalis

Abstract

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.

Controlled Delivery Formulations

“…The special volume includes three publications in which mesoporous silica particles have been used as a vehicle to reach a drug controlled release and a review about the possibilities of mesoporous materials in cancer treatment [1][2][3][4]. The publication by Harun et al [1] focused on the design, synthesis and characterization of a mesoporous formulation in order to improve the biopharmaceutical properties of the ruthenium polypyridyl complex [Ru(dppz)2PIP]2+ (dppz: dipyridophenazine, PIP: (2-(phenyl)imidazo [4,5-f][1,10]phenanthroline).…”

“…The work entitled "pH-Dependent Molecular Gate Mesoporous Microparticles for Biological Control of Giardia intestinalis" published by my research group in collaboration with Dr. Martinez-Mañez's group describes a new formulation of metronidazol encapsulated in mesoporous microparticles but, in this case, gated with a pH dependent molecular gate [2]. The new formulation allows drug delivery in duodenum, specifically reaching high drug concentrations in the place where a specific parasite is located.…”