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Uday B. Kompella - One of the best experts on this subject based on the ideXlab platform.
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Preparation of Large Porous Deslorelin-PLGA Microparticles with Reduced Residual Solvent and Cellular Uptake Using a Supercritical Carbon Dioxide Process
Pharmaceutical Research, 2004Co-Authors: Kavitha Koushik, Uday B. KompellaAbstract:Purpose. The purpose of this study was to prepare large-porous peptide-encapsulating polymeric particles with low residual solvent that retain deslorelin integrity, sustain drug release, and exhibit reduced epithelial and macrophage uptake. We hypothesized that supercritical Carbon Dioxide (SC CO_2) pressure-quench treatment of microparticles prepared using conventional approach expands these particles and extracts the residual organic solvent. Methods. Initial studies with crystalline L-lactide (L-PLA) and amorphous copolymers of lactide-co-glycolide (PLGA) 50:50, 65:35, and 75:25 indicated that PLGA 50:50 was the most amenable to morphological changes upon SC CO_2 treatment. Therefore, we prepared deslorelin-PLGA (50:50) microparticles using the conventional emulsion-solvent evaporation method, and in a second step equilibrated with SC CO_2 at various temperatures (33-37°C) and pressures (1200-2000 psi) for discrete intervals followed by rapid isothermal depressurization. The particles were then characterized for morphology, polymer thermal properties, particle size, porosity, bulk density, and residual solvent content. Also, deslorelin integrity, conformation, release, and cellular uptake before and after SC CO_2 treatment was determined. Results. Upon SC CO_2 treatment (1200 psi, 33°C for 30 min), the mean particle size of the deslorelin PLGA microparticles increased from 2.2 to 13.8 μm, the mean porosity increased from 39 to 92.38%, the mean pore diameter increased from 90 to 190 nm, the mean bulk density reduced from 0. 7 to 0.082 g/cc, mass spectrometry indicated structural integrity of released deslorelin, the circular dichroism spectrum indicated stabilization of β-turn conformation, and the scanning electron microscopy confirmed increased particle size and pore formation. The deslorelin release was sustained during the 7-day study period. Also, the peak Tg of PLGA decreased from 51 to 45°C, and the residual solvent content was reduced from 4500 ppm to below detection limit (< 25 ppm). The accumulation of drug from SC CO_2 treated particles in cell layers of Calu-3, A549, and rat alveolar macrophages was reduced by 87, 91 and 50%, respectively, compared to untreated particles. Conclusion. An SCF-derived Process could be successfully applied to prepare large porous deslorelin-PLGA particles with reduced residual solvent content, which retained deslorelin integrity, sustained deslorelin release, and reduced cellular uptake.
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Preparation of Large Porous Deslorelin-PLGA Microparticles with Reduced Residual Solvent and Cellular Uptake Using a Supercritical Carbon Dioxide Process
Pharmaceutical research, 2004Co-Authors: Kavitha Koushik, Uday B. KompellaAbstract:Purpose. The purpose of this study was to prepare large-porous peptide-encapsulating polymeric particles with low residual solvent that retain deslorelin integrity, sustain drug release, and exhibit reduced epithelial and macrophage uptake. We hypothesized that supercritical Carbon Dioxide (SC CO2) pressure-quench treatment of microparticles prepared using conventional approach expands these particles and extracts the residual organic solvent.
Kavitha Koushik - One of the best experts on this subject based on the ideXlab platform.
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Preparation of Large Porous Deslorelin-PLGA Microparticles with Reduced Residual Solvent and Cellular Uptake Using a Supercritical Carbon Dioxide Process
Pharmaceutical Research, 2004Co-Authors: Kavitha Koushik, Uday B. KompellaAbstract:Purpose. The purpose of this study was to prepare large-porous peptide-encapsulating polymeric particles with low residual solvent that retain deslorelin integrity, sustain drug release, and exhibit reduced epithelial and macrophage uptake. We hypothesized that supercritical Carbon Dioxide (SC CO_2) pressure-quench treatment of microparticles prepared using conventional approach expands these particles and extracts the residual organic solvent. Methods. Initial studies with crystalline L-lactide (L-PLA) and amorphous copolymers of lactide-co-glycolide (PLGA) 50:50, 65:35, and 75:25 indicated that PLGA 50:50 was the most amenable to morphological changes upon SC CO_2 treatment. Therefore, we prepared deslorelin-PLGA (50:50) microparticles using the conventional emulsion-solvent evaporation method, and in a second step equilibrated with SC CO_2 at various temperatures (33-37°C) and pressures (1200-2000 psi) for discrete intervals followed by rapid isothermal depressurization. The particles were then characterized for morphology, polymer thermal properties, particle size, porosity, bulk density, and residual solvent content. Also, deslorelin integrity, conformation, release, and cellular uptake before and after SC CO_2 treatment was determined. Results. Upon SC CO_2 treatment (1200 psi, 33°C for 30 min), the mean particle size of the deslorelin PLGA microparticles increased from 2.2 to 13.8 μm, the mean porosity increased from 39 to 92.38%, the mean pore diameter increased from 90 to 190 nm, the mean bulk density reduced from 0. 7 to 0.082 g/cc, mass spectrometry indicated structural integrity of released deslorelin, the circular dichroism spectrum indicated stabilization of β-turn conformation, and the scanning electron microscopy confirmed increased particle size and pore formation. The deslorelin release was sustained during the 7-day study period. Also, the peak Tg of PLGA decreased from 51 to 45°C, and the residual solvent content was reduced from 4500 ppm to below detection limit (< 25 ppm). The accumulation of drug from SC CO_2 treated particles in cell layers of Calu-3, A549, and rat alveolar macrophages was reduced by 87, 91 and 50%, respectively, compared to untreated particles. Conclusion. An SCF-derived Process could be successfully applied to prepare large porous deslorelin-PLGA particles with reduced residual solvent content, which retained deslorelin integrity, sustained deslorelin release, and reduced cellular uptake.
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Preparation of Large Porous Deslorelin-PLGA Microparticles with Reduced Residual Solvent and Cellular Uptake Using a Supercritical Carbon Dioxide Process
Pharmaceutical research, 2004Co-Authors: Kavitha Koushik, Uday B. KompellaAbstract:Purpose. The purpose of this study was to prepare large-porous peptide-encapsulating polymeric particles with low residual solvent that retain deslorelin integrity, sustain drug release, and exhibit reduced epithelial and macrophage uptake. We hypothesized that supercritical Carbon Dioxide (SC CO2) pressure-quench treatment of microparticles prepared using conventional approach expands these particles and extracts the residual organic solvent.
Rahmi Ozisik - One of the best experts on this subject based on the ideXlab platform.
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enhanced electromagnetic interference shielding effectiveness of polyCarbonate graphene nanocomposites foamed via 1 step supercritical Carbon Dioxide Process
Materials & Design, 2016Co-Authors: Marcelo Antunes, Gabriel Gedler, José Ignacio Velasco, Rahmi OzisikAbstract:Abstract The dielectric and electromagnetic interference (EMI) shielding properties of polyCarbonate/graphene nanocomposites foamed using supercritical Carbon Dioxide were studied as a function of their cellular and composite morphology. Foamed polyCarbonate filled with 0.5% (by weight) graphene exhibited enhanced EMI shielding effectiveness, which was found to depend on cellular and composite morphology in a complex manner. Foamed composites presented a maximum specific EMI shielding effectiveness of ~ 39 dB cm3/g, which is approximately 35 times greater than that of unfoamed composite (1.1 dB cm3/g). In addition, the relative permittivity was found to increase up to 3.25 times. The results suggest that graphene filled polymer foams can enhance the performance of electronic devices, opening up the possibility of using these materials in electronic applications.
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Enhanced electromagnetic interference shielding effectiveness of polyCarbonate/graphene nanocomposites foamed via 1-step supercritical Carbon Dioxide Process
Materials & Design, 2016Co-Authors: Gabriel Gedler, Marcelo Antunes, José Ignacio Velasco, Rahmi OzisikAbstract:Abstract The dielectric and electromagnetic interference (EMI) shielding properties of polyCarbonate/graphene nanocomposites foamed using supercritical Carbon Dioxide were studied as a function of their cellular and composite morphology. Foamed polyCarbonate filled with 0.5% (by weight) graphene exhibited enhanced EMI shielding effectiveness, which was found to depend on cellular and composite morphology in a complex manner. Foamed composites presented a maximum specific EMI shielding effectiveness of ~ 39 dB cm3/g, which is approximately 35 times greater than that of unfoamed composite (1.1 dB cm3/g). In addition, the relative permittivity was found to increase up to 3.25 times. The results suggest that graphene filled polymer foams can enhance the performance of electronic devices, opening up the possibility of using these materials in electronic applications.
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Controlling Foam Morphology of Poly(methyl methacrylate) via Surface Chemistry and Concentration of Silica Nanoparticles and Supercritical Carbon Dioxide Process Parameters
Journal of Chemistry, 2013Co-Authors: Deniz Rende, Linda S. Schadler, Rahmi OzisikAbstract:Polymer nanocomposite foams have received considerable attention because of their potential use in advanced applications such as bone scaffolds, food packaging, and transportation materials due to their low density and enhanced mechanical, thermal, and electrical properties compared to traditional polymer foams. In this study, silica nanofillers were used as nucleating agents and supercritical Carbon Dioxide as the foaming agent. The use of nanofillers provides an interface upon which CO2 nucleates and leads to remarkably low average cell sizes while improving cell density (number of cells per unit volume). In this study, the effect of concentration, the extent of surface modification of silica nanofillers with CO2-philic chemical groups, and supercritical Carbon Dioxide Process conditions on the foam morphology of poly(methyl methacrylate), PMMA, were systematically investigated to shed light on the relative importance of material and Process parameters. The silica nanoparticles were chemically modified with tridecafluoro-1,1,2,2-tetrahydrooctyl triethoxysilane leading to three different surface chemistries. The silica concentration was varied from 0.85 to 3.2% (by weight). The supercritical CO2 foaming was performed at four different temperatures (40, 65, 75, and 85°C) and between 8.97 and 17.93 MPa. By altering the surface chemistry of the silica nanofiller and manipulating the Process conditions, the average cell diameter was decreased from to μm, whereas, the cell density was increased from to cells/cm3. Our findings indicate that surface modification of silica nanoparticles with CO2-philic surfactants has the strongest effect on foam morphology.
Kazumi Danjo - One of the best experts on this subject based on the ideXlab platform.
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Dual imaging of pulmonary delivery and gene expression of dry powder inhalant by fluorescence and bioluminescence.
Journal of controlled release : official journal of the Controlled Release Society, 2008Co-Authors: Tomoyuki Mizuno, Kazumi Danjo, Kohta Mohri, Shiho Nasu, Hirokazu OkamotoAbstract:In gene therapy with an inhalant, therapeutic outcome depends on both the pulmonary delivery of the agent and the gene expression properties in the lung. The aim of the present study was to visualize and evaluate both the pulmonary delivery and the gene expression properties of a dry powder at once in mice. We used indocyanine green (ICG) as a fluorescent label, the plasmid DNA pCMV-Luc encoding the firefly luciferase as a reporter, chitosan as a non-viral vector and lactose as a carrier of the dry powder prepared by a supercritical Carbon Dioxide Process. The pulmonary delivery of the dry powder and the gene expression in the lung were evaluated by detection of fluorescence of ICG and the detection of luciferase activity, respectively, by using a real-time in vivo imaging system (IVIS® imaging system, Xenogen Corporation). The fluorescence and bioluminescence were more specifically detected by measuring from the back of the mice. We succeeded in visualizing both the pulmonary delivery and the gene expression in the same mouse that correlated with each other. In conclusion, the dry powder containing both ICG and pCMV-Luc was useful as a dual imaging system to visualize pulmonary delivery and gene expression in mice.
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Stability of chitosan–pDNA complex powder prepared by supercritical Carbon Dioxide Process
International Journal of Pharmaceutics, 2005Co-Authors: Hirokazu Okamoto, Yuki Sakakura, Keiko Shiraki, Kumiko Oka, Seiko Nishida, Hiroaki Todo, Kotaro Iida, Kazumi DanjoAbstract:Abstract The present study examined the stability of a gene in powders prepared with supercritical Carbon Dioxide (CO 2 ) from the viewpoints of the ternary structure of DNA and in vivo transfection potential. An aqueous chitosan–pCMV-Luc complex solution containing mannitol was injected into the stream of a supercritical CO 2 /ethanol admixture to precipitate a gene powder. The obtained gene powders and gene solutions were placed in stability chambers at 25 or 40 °C for 4 weeks. The integrity and transfection potency of the gene were examined by electrophoresis and in vivo pulmonary transfection study in mice. The supercritical CO 2 Process decreased the supercoiled DNA during the manufacturing Process; however, the decrease in the remaining supercoiled and open circular DNA in the powders during storage was much slower than that in solutions. In addition, the powders had higher transfection potency than the solutions containing the same amount of DNA. The effect of chitosan on the stability of DNA in solutions was not obvious in the solutions but it improved the stability of DNA in powders during manufacturing and storage. Thus, a gene powder with a cationic vector is a promising ready-to-use formulation for inhalation therapy of pulmonary diseases.
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Stability of chitosan-pDNA complex powder prepared by supercritical Carbon Dioxide Process.
International journal of pharmaceutics, 2005Co-Authors: Hirokazu Okamoto, Yuki Sakakura, Keiko Shiraki, Kumiko Oka, Seiko Nishida, Hiroaki Todo, Kotaro Iida, Kazumi DanjoAbstract:The present study examined the stability of a gene in powders prepared with supercritical Carbon Dioxide (CO(2)) from the viewpoints of the ternary structure of DNA and in vivo transfection potential. An aqueous chitosan-pCMV-Luc complex solution containing mannitol was injected into the stream of a supercritical CO(2)/ethanol admixture to precipitate a gene powder. The obtained gene powders and gene solutions were placed in stability chambers at 25 or 40 degrees C for 4 weeks. The integrity and transfection potency of the gene were examined by electrophoresis and in vivo pulmonary transfection study in mice. The supercritical CO(2) Process decreased the supercoiled DNA during the manufacturing Process; however, the decrease in the remaining supercoiled and open circular DNA in the powders during storage was much slower than that in solutions. In addition, the powders had higher transfection potency than the solutions containing the same amount of DNA. The effect of chitosan on the stability of DNA in solutions was not obvious in the solutions but it improved the stability of DNA in powders during manufacturing and storage. Thus, a gene powder with a cationic vector is a promising ready-to-use formulation for inhalation therapy of pulmonary diseases.
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Improvement of insulin absorption from intratracheally administrated dry powder prepared by supercritical Carbon Dioxide Process
Journal of pharmaceutical sciences, 2003Co-Authors: Hiroaki Todo, Hirokazu Okamoto, Kotaro Iida, Kazumi DanjoAbstract:The purpose of this study was to improve insulin absorption from dry powder after administration in lung without an absorption enhancer. The dry powders, with mannitol as a carrier, were prepared with or without an absorption enhancer (citric acid) by supercritical Carbon Dioxide (SCF) and spray drying (SD) Processes. Insulin powder was precipitated from dimethyl sulfoxide and aqueous solutions by dispersing the insulin solutions from parallel and V-type nozzles, respectively, into supercritical Carbon Dioxide, which is an antisolvent for insulin. In vitro aerosol performance was evaluated with a cascade impactor. Insulin powder containing citric acid prepared by the SCF method (MIC SCF) showed improved inhalation performance compared with insulin powder prepared by the SD Process, although the particle size of the former powder was larger than that in powders prepared by SD. Insulin absorption was estimated from the change in plasma glucose level. The blood glucose level after administration of the insulin powder without citric acid prepared by the SCF Process (MI SCF) decreased rapidly, and a significant difference was observed for areas under the curve of change in plasma glucose concentration versus time (AUCs) between MI SCF and the insulin powder without citric acid prepared by the SD Process (MI SD). These results suggest that the SCF technique would be useful to prepare dry powders suitable for inhalation.
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Pulmonary Gene Delivery by Chitosan–pDNA Complex Powder Prepared by a Supercritical Carbon Dioxide Process
Journal of pharmaceutical sciences, 2003Co-Authors: Hirokazu Okamoto, Yuki Sakakura, Seiko Nishida, Hiroaki Todo, Kotaro Iida, Kazumi DanjoAbstract:ABSTRACT: Chitosan–plasmid DNA (pDNA) complex powders as a pulmonary gene delivery system were prepared with a supercritical Carbon Dioxide (CO 2 ) Process and their in vivo activity was evaluated. The powders with mannitol as a carrier were prepared by dispersing aqueous solutions of a luciferase expression plasmid driven by the cytomegalovirus promoter (pCMV–Luc) with or without chitosan as a cationic vector in a supercritical CO 2 /ethanol admixture. The supercritical CO 2 Process with a V-shaped nozzle successfully produced chitosan–pDNA powders. The addition of chitosan suppressed the degradation of pCMV–Luc during the supercritical CO 2 Process and increased the yield of powders. The luciferase activity in mouse lung was evaluated after pulmonary administration of the powders or pCMV–Luc solutions. The chitosan–pDNA powders increased the luciferase activity in mouse lung compared with pCMV–Luc powders without chitosan or pCMV–Luc solutions with or without chitosan. The chitosan–pDNA powder with an N/P ratio = 5 increased the luciferase activity to 2700% of that of the pCMV–Luc solution. These results suggest that gene powder with chitosan is a useful pulmonary gene delivery system.
Gabriel Gedler - One of the best experts on this subject based on the ideXlab platform.
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enhanced electromagnetic interference shielding effectiveness of polyCarbonate graphene nanocomposites foamed via 1 step supercritical Carbon Dioxide Process
Materials & Design, 2016Co-Authors: Marcelo Antunes, Gabriel Gedler, José Ignacio Velasco, Rahmi OzisikAbstract:Abstract The dielectric and electromagnetic interference (EMI) shielding properties of polyCarbonate/graphene nanocomposites foamed using supercritical Carbon Dioxide were studied as a function of their cellular and composite morphology. Foamed polyCarbonate filled with 0.5% (by weight) graphene exhibited enhanced EMI shielding effectiveness, which was found to depend on cellular and composite morphology in a complex manner. Foamed composites presented a maximum specific EMI shielding effectiveness of ~ 39 dB cm3/g, which is approximately 35 times greater than that of unfoamed composite (1.1 dB cm3/g). In addition, the relative permittivity was found to increase up to 3.25 times. The results suggest that graphene filled polymer foams can enhance the performance of electronic devices, opening up the possibility of using these materials in electronic applications.
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Enhanced electromagnetic interference shielding effectiveness of polyCarbonate/graphene nanocomposites foamed via 1-step supercritical Carbon Dioxide Process
Materials & Design, 2016Co-Authors: Gabriel Gedler, Marcelo Antunes, José Ignacio Velasco, Rahmi OzisikAbstract:Abstract The dielectric and electromagnetic interference (EMI) shielding properties of polyCarbonate/graphene nanocomposites foamed using supercritical Carbon Dioxide were studied as a function of their cellular and composite morphology. Foamed polyCarbonate filled with 0.5% (by weight) graphene exhibited enhanced EMI shielding effectiveness, which was found to depend on cellular and composite morphology in a complex manner. Foamed composites presented a maximum specific EMI shielding effectiveness of ~ 39 dB cm3/g, which is approximately 35 times greater than that of unfoamed composite (1.1 dB cm3/g). In addition, the relative permittivity was found to increase up to 3.25 times. The results suggest that graphene filled polymer foams can enhance the performance of electronic devices, opening up the possibility of using these materials in electronic applications.