摘要：

A system to deliver bioactive calcium phosphate nanoparticles (about 60 nm, loaded with nucleic acids) across the stomach into the colon was developed by freezeヾrying the nanoparticles in the presence of the cryoprotectant trehalose, incorporation into gelatin capsules, and coating the capsules with an enteric polymer. These capsules were stable at pH 1 (stomach conditions) and dissolved at pH 7.1 (colon conditions). The nanoparticles were released after about 60–120 min at pH 7.1. Cell culture experiments with HeLa and Cacocells showed an uptake of the nanoparticles, a transfection with EGFP〆ncoding plasmid DNA, and a gene﹕ilencing with anti〦GFP siRNA. From a variety of enteric coating polymers, the systems cellulose acetate phthalate (CAP), hydroxypropylmethylcellulose〦udragit L100, and hydroxypropylmethylcellulose﹑olyvinylalcohol〦udragit L100 were the most suitable to accomplish the desired biological effect. The presented method is applicable for colon therapy, e. g. for an oral administration of bioactive nanoparticles which are sensitive to acidic conditions. Bioactive calcium phosphate nanoparticles can be delivered to the colon inside polymerヽoated gelatin capsules that survive the acidic stomach conditions. They are delivering their cargo (nucleic acids) for local gene delivery, i. e. transfection or gene silencing. This opens the way for an oral delivery of acid﹕ensitive nanoparticle for local gene transfer to regulate local protein synthesis via upor downregulation.

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