Hybrid Organomineral Carriers for Therapeutic Proteins

Abstract

—Drug delivery systems are developed to provide a necessary concentration and prolonged effect of the active substance in the organism. Orally administered protein preparations require a protection from the proteolysis in the gastrointestinal tract. Biocompatible hydrophilic polysaccharides in the composition of the matrix are especially promising, since they do not irritate the intestine and are gradually cleaved by specific glycosidases, releasing a therapeutic agent. The introduction of an insoluble porous mineral matrix into the composition of the carrier allows us to increase the concentration of the therapeutic agent in the matrix without a significant increase in the volume of the drug tablet form. In this work, a new original organomineral carrier was created based on heat-treated crushed clinoptilolite zeolite in combination with natural polysaccharides of red algae (agar–agar, agarose, and carrageenan). Granular and finely dispersed clinoptilolites in the composition of the matrix are loaded with a promising therapeutic agent (Bacillus pumilus ribonuclease (binase)), which shows a selective cytotoxicity to tumor cells. It was established that both granular and finely dispersed zeolites in a complex with polysaccharides retain the protein better as compared with pure zeolites and provide a gradual complete release of the enzyme in 18 h; at the same time, binase retains a catalytic activity and causes apoptosis in up to 23.8% of the population of HuTu80 human duodenal adenocarcinoma cells. Data obtained substantiate the prospects of designing dosage forms based on the studied organomineral carriers.