Preparation of Calcium Phosphate Nanocapsule Including Acid-Polyethyleneimine-Hyaluronic Acid Ternary Complex for Durable Gene Delivery

Our plasmid delivery systems comprising deoxyribonucleic acid (DNA), polyethyleneimine (PEI), and hyaluronic acid (HA) have already achieved the high-extragene expression in tumor tissues. Repeated transfection with certain cytokine genes effectively induced tumor regression and complete disappearance of the tumor in some cases. Frequent injection is sometimes difficult depending on the tumor site. However, single injection often leads to an unsatisfactory efficacy owing to the short duration of the gene expression. In this study, we prepared calcium phosphate (CaP) nanocapsule including plasmid DNA complexes as a durable gene transfection system, which would be slowly degraded, and release DNA complex in the body. CaP nanocupsule including DNA complexes with a diameter of approximately 200 nm was prepared by immersing HA-coated DNA-PEI complex in simulated body fluid. It showed gene expression in cultured cells with duration longer than 2 weeks. By this slow-releasing system, significant tumor-growth suppression and, finally, complete tumor disappearance were observed after single injection into the tumor. Capsulated DNA complex with Ca thus seems promising as a sustained gene expression device. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:179-184, 2014