The formation of plasmid DNA loaded pharmaceutical powders using supercritical fluid technology

Tservistas, Markus; Levy, M. Susana; Lo-Yim, M.Y.A.; O’Kennedy, Ronan; York, Peter; Humphrey, G.O.; Hoare, M.

doi:10.1002/1097-0290(20010105)72:1<12::aid-bit2>3.0.co;2-z

Cited by 58 publications

(37 citation statements)

References 35 publications

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“…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. SFD uses a spray nozzle, liquid nitrogen, and a lyophilizer.…”

supporting

confidence: 79%

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

Suzuki

Okuda

Okamoto

2016

Biological & Pharmaceutical Bulletin

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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.

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supporting

confidence: 79%

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

Suzuki

Okuda

Okamoto

2016

Biological & Pharmaceutical Bulletin

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“…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: 54%

“…Tservistas et al clarified that the acidic conditions caused by supercritical CO 2 with water destabilized pDNA during production of the powder. 25) Thus, similar destabilization may have occurred to siRNA in our study. On the other hand, the addition of chitosan could improve siRNA integrity in the powder (Fig.…”

Section: Discussionmentioning

confidence: 89%

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

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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.

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“…These excipients and the precipitation regime need to be carefully selected to avoid potential solid-phase separation between the drug and excipient molecules with consequent loss of intimate molecular bonding. Such co-precipitation is likely to improve both the processability and stability of the resulting material (238). ChitosanYplasmid DNA complex powders were obtained with mannitol as a carrier using SAS (238).…”

Section: Precipitation Of Biological and Composite Materials Using Sasmentioning

confidence: 99%

“…Such co-precipitation is likely to improve both the processability and stability of the resulting material (238). ChitosanYplasmid DNA complex powders were obtained with mannitol as a carrier using SAS (238). The chitosan complexation not only suppressed the degradation of the bioactive pCMV-Luc during the SCF precipitation, but also increased the yield and the luciferase activity in the mouse lungs compared to pCMV-Luc without chitosan or pCMVLuc solutions with or without chitosan.…”

Section: Precipitation Of Biological and Composite Materials Using Sasmentioning

confidence: 99%

Particle Engineering for Pulmonary Drug Delivery

et al. 2007

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With the rapidly growing popularity and sophistication of inhalation therapy, there is an increasing demand for tailor-made inhalable drug particles capable of affording the most efficient delivery to the lungs and the most optimal therapeutic outcomes. To cope with this formulation demand, a wide variety of novel particle technologies have emerged over the past decade. The present review is intended to provide a critical account of the current goals and technologies of particle engineering for the development of pulmonary drug delivery systems. These technologies cover traditional micronization and powder blending, controlled solvent crystallization, spray drying, spray freeze drying, particle formation from liquid dispersion systems, supercritical fluid processing and particle coating. The merits and limitations of these technologies are discussed with reference to their applications to specific drug and/or excipient materials. The regulatory requirements applicable to particulate inhalation products are also reviewed briefly.

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The formation of plasmid DNA loaded pharmaceutical powders using supercritical fluid technology

Cited by 58 publications

References 35 publications

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

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

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

Particle Engineering for Pulmonary Drug Delivery

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