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Calcium phosphate nanoparticles (diameter about 60 nm, triple‐shell) were loaded with nucleic acids (DNA or siRNA) for local gene therapy in the colon. To avoid the oral administration where a passage through the stomach is necessary, the nanoparticles were incorporated into custom‐made hard‐fat suppositories after freeze‐drying with trehalose. After melting the suppository at 37°C, the nanoparticles were released and well dispersed in cell culture medium. They retained their bioactivity as shown by in vitro cell culture studies with the model cell line HeLa and the colon cancer cell line Caco‐2. The nanoparticles were easily taken up by both cell types and also efficient for transfection and gene silencing, as shown with the model protein eGFP. This opens a way for local gene therapy in the colon. [ABSTRACT FROM AUTHOR]

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‐drying 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 Caco‐2 cells showed an uptake of the nanoparticles, a transfection with EGFP‐encoding plasmid DNA, and a gene‐silencing with anti‐EGFP siRNA. From a variety of enteric coating polymers, the systems cellulose acetate phthalate (CAP), hydroxypropylmethylcellulose‐Eudragit L100, and hydroxypropylmethylcellulose‐polyvinylalcohol‐Eudragit 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. [ABSTRACT FROM AUTHOR]

Two ways to deliver ultrasmall gold nanoparticles and gold-bovine serum albumin (BSA) nanoclusters to the colon were developed. First, oral administration is possible by incorporation into gelatin capsules that were coated with an enteric polymer. These permit the transfer across the stomach whose acidic environment damages many drugs. The enteric coating dissolves due to the neutral pH of the colon and releases the capsule's cargo. Second, rectal administration is possible by incorporation into hard-fat suppositories that melt in the colon and then release the nanocarriers. The feasibility of the two concepts was demonstrated by in-vitro release studies and cell culture studies that showed the easy redispersibility after dissolution of the respective transport system. This clears a pathway for therapeutic applications of drug-loaded nanoparticles to address colon diseases, such as chronic inflammation and cancer. [ABSTRACT FROM AUTHOR]