title: Development of New Formulation Dry Powder for Pulmonary Delivery Using Amino Acids to Improve Stability.
abstract: Cationic polymers are being studied as non-viral gene delivery vectors. Poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (PAsp(DET)) and their block copolymers with poly(ethylene glycol), PEG-PAsp(DET), have been reported as efficient biodegradable non-viral vectors which form a polyplex with plasmid DNA (pDNA). However, the polyplexes are not stable because PAsp(DET) and PEG-PAsp(DET) are easily subjected to hydrolysis; therefore, they need to be prepared on site. In this study, using the biodegradable polycations as non-viral vectors, PAsp(DET) and PEG-PAsp(DET), we investigated the effects of L-leucine (Leu) on the polyplex. We prepared solutions and dry powders with and without Leu. Both dry powders had large and porous particles and Leu acted as a dispersing agent. The transfection activity of the sample solutions decreased within a month. However, the decrease in the transfection activity was partially suppressed by the dry powder with Leu at 5 and 25°C at 3 months. Furthermore, transfection experiments revealed that Leu exhibited a pDNA-stabilizing effect in the solution and dry powder. Similar results were observed for pDNA integrity, where a polyplex was formed in the dry powder. The results suggest that Leu is a candidate stabilizer to protect pDNA from degradation.
authors.affiliation: Faculty of Pharmacy, Meijo University.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Okuda
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D015870:Gene Expression; D007930:Leucine / Q000737:chemistry*; D049409:Luciferases, Firefly / Q000235:genetics; D051379:Mice; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D010957:Plasmids; D011092:Polyethylene Glycols / Q000737:chemistry*; D011208:Powders
chemical_list: C539404:PAsp(DET); D010455:Peptides; D011208:Powders; D011092:Polyethylene Glycols; D004247:DNA; D049409:Luciferases, Firefly; D007930:Leucine