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The development of efficient and selective therapeutic gene delivery methods is a potential medical treatment for intractable diseases. Dry powder inhalers (DPIs) can efficiently deliver drugs locally to the lung. Many reports discuss preparation methods for DPIs. Spray-freeze drying is a method by which highly porous particulates can be prepared. However, altered physical properties after preparation may result in changes in gene expression. In this study, bovine serum albumin (BSA) was added as a lyoprotectant, and 1,2-dioleoyl-3-trimethylammonium propane/cholesterol liposomes/pCMV-Luc DPIs (lipoplex DPIs) were prepared by spray-freeze drying. The mean particle sizes of the lipoplex DPIs prepared without BSA increased by approximately 6.7-fold compared with that of the lipoplexes solution. In contrast, the mean particle sizes of the lipoplex/BSA DPIs increased only slightly. Gene expression was evaluated after the intratracheal administration of the lipoplexes solution, with maximum gene expression observed at 12 h after the administration. In contrast, maximum gene expression of the lipoplex/BSA DPIs occurred at 6 h after administration. The gene expression associated with the lipoplex DPIs was significantly lower compared with that of the lipoplex/BSA DPIs at 6 (p<0.01), 12 (p<0.01), and 24 h (p<0.05). These variances may be due to the difference in mean particle size between the DPI formulations. The results suggest that BSA is a useful lyoprotectant for dry powder formulation preparations of DNA using the spray-freeze drying method, given that the preparation results in minimal variation of physical properties and gene expression.Key words dry powder inhaler; spray-freeze drying; lyoprotectant; bovine serum albumin; pulmonary gene delivery; lipoplex Gene therapy is expected to be a cure for intractable diseases. However, efficient and selective delivery of therapeutic genes to the target cells is necessary for gene therapy to be effective.1) Although viral vectors may show high gene expression, toxicity as a result of immunogenicity is a major problem associated with their use. Therefore, non-viral vectors have received attention because of their relatively low toxicity. 2)Many researchers have demonstrated that cationic liposomes show high gene expression and low toxicity.3-5) Lung diseases such as lung cancer and cystic fibrosis are intractable, and therefore, the realization of efficient gene therapy to treat such conditions is essential. However, the development of delivery methods that enable the local delivery of therapeutic genes to the lung is needed.The aerosolization of gene vectors is an efficient delivery method, and many related studies have been carried out. 6,7)However, it is necessary for aerosols to be sprayed immediately because the stability of gene vectors in aqueous solution is low. 8) Alternatively, dry powder inhalers (DPIs) are widely used and accepted as an effective system for pulmonary drug delivery. DPIs have many advantages, including increased shelf life of drugs including pla...

Double-chain ammonium amphiphiles that contain the carbazole ring formed stable monolayers on water. Their fluorescence patterns indicated different packing modes of the chromophore which depended on chemical structure and component distribution.