Pulmonary Gene Delivery by Chitosan–pDNA Complex Powder Prepared by a Supercritical Carbon Dioxide Process

Okamoto, Hirokazu; Nishida, Seiko; Todo, Hiroaki; Sakakura, Yuki; Iida, Kotaro; Danjo, Kazumi

doi:10.1002/jps.10285

Cited by 97 publications

(52 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Enhanced pulmonary transfection was also observed using a dry pDNA/chitosan powder, as shown in our previous reports. 26,29) Although it is still unclear why the siRNA/chitosan powder had a great in-vivo gene silencing effect than did the siRNA/chitosan solution, the difference is likely related to the biodistribution of siRNA (Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

“…[26][27][28][29] The apparatus for preparing the powders was assembled by JASCO Co., Tokyo, Japan and composed of pumps (for CO 2 , ethanol, and water), an oven, and a back pressure regulator. In brief, all components (total mass; 50 mg), as listed in Table 1, were dissolved in 1 mL of water.…”

Section: Methodsmentioning

confidence: 99%

“…In our and the previous reports, dry plasmid DNA (pDNA) powders could be stably prepared by the supercritical CO 2 technique. [25][26][27][28][29] We demonstrated that a pDNA powder prepared with chitosan, a biodegradable cationic polymer, exhibited a greater pulmonary gene expressing effect and longer storage than did the solution. 26,27) These observations prompted us to use the supercritical CO 2 technique to prepare inhalable siRNA powders.…”

mentioning

confidence: 89%

See 2 more Smart Citations

Gene Silencing in a Mouse Lung Metastasis Model by an Inhalable Dry Small Interfering RNA Powder Prepared Using the Supercritical Carbon Dioxide Technique

Okuda

Kito

Oiwa

et al. 2013

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

In this study, a novel dry small interfering RNA (siRNA) powder for inhalation, containing chitosan and mannitol, was prepared using the supercritical carbon dioxide (CO 2 ) technique. Although the siRNA/chitosan powder was difficult to disperse because of a long needle-like structure, it could be reduced to fragments of 10-20 µm by manual grinding, which allowed for administration into mice. Electrophoresis revealed that the supercritical CO 2 technique and manual grinding didn't greatly affect the integrity of the siRNA. Furthermore, the siRNA was more stable in the lungs than in blood, suggesting the utility of pulmonary delivery. Biodistribution experiments using Cy5.5-labeled siRNA demonstrated that pulmonary administration of the powder achieved a prolonged exposure of the siRNA/chitosan complex on the lung epithelial surface at a higher concentration. For the evaluation of the in-vivo gene silencing effect of the siRNA/chitosan powder, mice bearing colon26/Luc cells were used. The powder significantly inhibited the increase in luminescence intensity in the lungs, but the siRNA/chitosan solution and a non-specific dry siRNA/chitosan powder didn't, indicating the effective and specific gene silencing against the tumor cells metastasized in the lungs of mice by the siRNA/chitosan powder. These results strongly indicate that inhalable dry siRNA powders have the possibility of effective pulmonary gene silencing and that the supercritical CO 2 technique can be applied to the production.Key words small interfering RNA; inhalable dry powder; supercritical fluid technique; pulmonary gene delivery; chitosan RNA interference (RNAi), first reported by Fire et al., is a unique cellular phenomenon in which double-stranded RNA (dsRNA) regulates gene expression, contributing to cellular defenses against viral infections and transposon expansion.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 89%

See 1 more Smart Citation

Gene Silencing in a Mouse Lung Metastasis Model by an Inhalable Dry Small Interfering RNA Powder Prepared Using the Supercritical Carbon Dioxide Technique

Okuda

Kito

Oiwa

et al. 2013

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, drying in supercritical CO 2 was used as a method to improve surface area of chitosan structures. 34 Application of this process allows the generation of porosity and enlarges the surface area (close to 110 m 2 · g -1 ) to be potentially used in catalysis. 35 Among other diverse fields, water treatment is an important field that can benefit from the advances in nanoscale science and engineering.…”

Section: Introductionmentioning

confidence: 99%

Sorption Efficiency of Chitosan Nanofibers toward Metal Ions at Low Concentrations

et al. 2010

View full text Add to dashboard Cite

Chitosan fibers showing narrow diameter distribution with a mean of 42 nm were produced by electrospinning and utilized for the sorption of Fe(III), Cu(II), Ag(I), and Cd(II) ions from aqueous solutions. The ion concentrations in the supernatant solutions were determined using inductively coupled plasma-mass spectrometry (ICP-MS). The filtration efficiency of the fibers toward these ions was studied by both batch and microcolumn methods. High efficiency in sorption of the metal ions was obtained in the both methods. The effects of sorbent amount (0.10-0.50 mg), shaking time (15-120 min), initial metal ion concentration (10.0-1000.0 µg · L -1 ), and temperature (25 and 50°C) on the extent of sorption were examined. The sorbent amount did not significantly alter the efficiency of sorption; however, shaking time, temperature, and metal ion concentration were found to have a strong influence on sorption. By virtue of its mechanical integrity, the applicability of the chitosan mat in solid phase extraction under continuous flow looks promising.

show abstract

“…21) Spray drying (SD), lyophilization, and supercritical fluid precipitation have been employed for the preparation of gene powders. 19,22,23) However, several stresses, including heating, freezing, spraying, and shear forces, must be considered to avoid destabilization of the gene or delivery system during powder production. [24][25][26][27] Spray-freeze-drying (SFD) is a relatively new technology for the production of inhalable powder drugs.…”

mentioning

confidence: 99%

Development of New Formulation Dry Powder for Pulmonary Delivery Using Amino Acids to Improve Stability

Suzuki

Okuda

Okamoto

2016

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Pulmonary Gene Delivery by Chitosan–pDNA Complex Powder Prepared by a Supercritical Carbon Dioxide Process

Cited by 97 publications

References 34 publications

Gene Silencing in a Mouse Lung Metastasis Model by an Inhalable Dry Small Interfering RNA Powder Prepared Using the Supercritical Carbon Dioxide Technique

Gene Silencing in a Mouse Lung Metastasis Model by an Inhalable Dry Small Interfering RNA Powder Prepared Using the Supercritical Carbon Dioxide Technique

Sorption Efficiency of Chitosan Nanofibers toward Metal Ions at Low Concentrations

Development of New Formulation Dry Powder for Pulmonary Delivery Using Amino Acids to Improve Stability

Contact Info

Product

Resources

About