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Philip Chi Lip Kwok - One of the best experts on this subject based on the ideXlab platform.
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using two fluid nozzle for spray freeze drying to produce porous Powder Formulation of naked sirna for inhalation
International Journal of Pharmaceutics, 2018Co-Authors: Wanling Liang, Michael Y T Chow, Shing Fung Chow, Hakkim Chan, Philip Chi Lip KwokAbstract:Abstract Spray freeze drying is an attractive technology to produce Powder Formulation for inhalation. It can be used to generate large porous particles which tend to aerosolize efficiently and do not aggregate readily. It also avoids material to be exposed to elevated temperature. In this study, we reported the use of two-fluid nozzle to produce spray freeze dried Powder of small interfering RNA (siRNA). The effect of atomization gas flow rate and liquid feed rate were inspected initially using herring sperm DNA (hsDNA) as nucleic acid model. The atomization gas flow rate was found to have a major impact on the aerosol properties. The higher the atomization gas flow rate, the smaller the particle size, the higher the fine particle fraction (FPF). In contrast, the liquid feed rate had very minor effect. Subsequently, spray freeze dried siRNA Powder was produced at various atomization gas flow rates. The particles produced were highly porous as examined with the scanning electron microscopy, and the structural integrity of the siRNA was demonstrated with gel electrophoresis. The gene-silencing effect of the siRNA was also successfully preserved in vitro. The best performing siRNA Formulation was prepared at the highest atomization gas flow rate investigated with a moderate FPF of 30%. However, this was significantly lower than that obtained with the corresponding hsDNA counterparts (FPF ∼57%). A direct comparison between the hsDNA and siRNA Formulations revealed that the former exhibited a lower density, hence a smaller aerodynamic diameter despite similar geometric size.
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inhaled Powder Formulation of naked sirna using spray drying technology with l leucine as dispersion enhancer
International Journal of Pharmaceutics, 2017Co-Authors: Michael Y T Chow, Hakkim Chan, Philip Chi Lip Kwok, Fiona F K LoAbstract:Abstract Pulmonary delivery of short interfering RNA (siRNA) has been widely studied in both animal and clinical studies to treat various respiratory diseases by gene silencing through RNA interference. Some of these studies showed that the administration of naked siRNA (without the use of any delivery vectors) could achieve satisfactory gene silencing effect, a unique feature to pulmonary delivery. Liquid aerosols were mostly used with very limited studies on the use of Powder aerosols for siRNA. In this study, siRNA was co-spray dried with mannitol and l -leucine, the latter being a dispersion enhancer. To the best of our knowledge, this is the first time that siRNA in its naked form was formulated into an inhalable dry Powder using spray drying technology. The aerosol performance of the Powder was evaluated by Next Generation Impactor (NGI). The presence of l -leucine in the Formulation could improve the aerosolization of siRNA-containing Powders. Results from the X-ray photoelectron spectroscopy (XPS) suggested that l -leucine was enriched on the particle surface and promote Powder dispersion. Among the different siRNA Formulations being examined, the one that contained 50% w/w of l -leucine exhibited the best aerodynamic performance, with a high emitted fraction (EF) of around 80% and a modest fine particle fraction (FPF) of 45%. Importantly, the integrity of siRNA was successfully retained as evaluated by gel retardation assay and high performance liquid chromatography (HPLC).
Michael Y T Chow - One of the best experts on this subject based on the ideXlab platform.
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effective mrna pulmonary delivery by dry Powder Formulation of pegylated synthetic kl4 peptide
Journal of Controlled Release, 2019Co-Authors: Qiuying Liao, Keshia L K Kung, Michael Y T ChowAbstract:Abstract Pulmonary delivery of messenger RNA (mRNA) has considerable potential as therapy or vaccine for a range of lung diseases. Inhaled dry Powder Formulation of mRNA is particularly attractive as it has superior stability and dry Powder inhaler is relatively easy to use. A safe and effective mRNA delivery vector as well as a suitable particle engineering method are required to produce a dry Powder Formulation that is respirable and mediates robust transfection in the lung. Here, we introduce a novel RNA delivery vector, PEG12KL4, in which the synthetic cationic KL4 peptide is attached to a monodisperse linear PEG of 12-mers. The PEG12KL4 formed nano-sized complexes with mRNA at 10:1 ratio (w/w) and mediated effective transfection on human lung epithelial cells. PEG12KL4/mRNA complexes were successfully formulated into dry Powder by spray drying (SD) and spray freeze drying (SFD) techniques. Both SD and SFD Powder exhibited satisfactory aerosol properties for inhalation. More importantly, the biological activity of the PEG12KL4 /mRNA complexes were successfully preserved after drying. Using luciferase mRNA, the intratracheal administration of the liquid or Powder aerosol of PEG12KL4 /mRNA complexes at a dose of 5 μg mRNA resulted in luciferase expression in the deep lung region of mice 24 h post-transfection. The transfection efficiency was superior to naked mRNA or lipoplexes (Lipofectamine 2000), in which luciferase expression was weaker and restricted to the tracheal region only. There was no sign of inflammatory response or toxicity of the PEG12KL4 /mRNA complexes after single intratracheal administration. Overall, PEG12KL4 is an excellent mRNA transfection agent for pulmonary delivery. This is also the first study that successfully demonstrates the preparation of inhalable dry Powder mRNA Formulations with in vivo transfection efficiency, showing the great promise of PEG12KL4 peptide as a mRNA delivery vector candidate for clinical applications.
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using two fluid nozzle for spray freeze drying to produce porous Powder Formulation of naked sirna for inhalation
International Journal of Pharmaceutics, 2018Co-Authors: Wanling Liang, Michael Y T Chow, Shing Fung Chow, Hakkim Chan, Philip Chi Lip KwokAbstract:Abstract Spray freeze drying is an attractive technology to produce Powder Formulation for inhalation. It can be used to generate large porous particles which tend to aerosolize efficiently and do not aggregate readily. It also avoids material to be exposed to elevated temperature. In this study, we reported the use of two-fluid nozzle to produce spray freeze dried Powder of small interfering RNA (siRNA). The effect of atomization gas flow rate and liquid feed rate were inspected initially using herring sperm DNA (hsDNA) as nucleic acid model. The atomization gas flow rate was found to have a major impact on the aerosol properties. The higher the atomization gas flow rate, the smaller the particle size, the higher the fine particle fraction (FPF). In contrast, the liquid feed rate had very minor effect. Subsequently, spray freeze dried siRNA Powder was produced at various atomization gas flow rates. The particles produced were highly porous as examined with the scanning electron microscopy, and the structural integrity of the siRNA was demonstrated with gel electrophoresis. The gene-silencing effect of the siRNA was also successfully preserved in vitro. The best performing siRNA Formulation was prepared at the highest atomization gas flow rate investigated with a moderate FPF of 30%. However, this was significantly lower than that obtained with the corresponding hsDNA counterparts (FPF ∼57%). A direct comparison between the hsDNA and siRNA Formulations revealed that the former exhibited a lower density, hence a smaller aerodynamic diameter despite similar geometric size.
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inhaled Powder Formulation of naked sirna using spray drying technology with l leucine as dispersion enhancer
International Journal of Pharmaceutics, 2017Co-Authors: Michael Y T Chow, Hakkim Chan, Philip Chi Lip Kwok, Fiona F K LoAbstract:Abstract Pulmonary delivery of short interfering RNA (siRNA) has been widely studied in both animal and clinical studies to treat various respiratory diseases by gene silencing through RNA interference. Some of these studies showed that the administration of naked siRNA (without the use of any delivery vectors) could achieve satisfactory gene silencing effect, a unique feature to pulmonary delivery. Liquid aerosols were mostly used with very limited studies on the use of Powder aerosols for siRNA. In this study, siRNA was co-spray dried with mannitol and l -leucine, the latter being a dispersion enhancer. To the best of our knowledge, this is the first time that siRNA in its naked form was formulated into an inhalable dry Powder using spray drying technology. The aerosol performance of the Powder was evaluated by Next Generation Impactor (NGI). The presence of l -leucine in the Formulation could improve the aerosolization of siRNA-containing Powders. Results from the X-ray photoelectron spectroscopy (XPS) suggested that l -leucine was enriched on the particle surface and promote Powder dispersion. Among the different siRNA Formulations being examined, the one that contained 50% w/w of l -leucine exhibited the best aerodynamic performance, with a high emitted fraction (EF) of around 80% and a modest fine particle fraction (FPF) of 45%. Importantly, the integrity of siRNA was successfully retained as evaluated by gel retardation assay and high performance liquid chromatography (HPLC).
Dexiang Chen - One of the best experts on this subject based on the ideXlab platform.
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Hepatitis-B surface antigen (HBsAg) Powder Formulation: process and stability assessment.
Current Drug Delivery, 2007Co-Authors: Mahmoud Ameri, Lendon G Payne, Cindy L. Zuleger, Jorge E. Osorio, Dexiang ChenAbstract:The purpose of this study was to develop a hepatitis-B surface antigen (HBsAg) dry Powder vaccine Formulation suitable for epidermal Powder immunization (EPI) via an efficient, scalable Powder-formation process. Several HBsAg dry Powder Formulations were prepared using four different Powder-formation methods: freezedrying/ compress/grind/sieve (FD/C/G/S), spray-drying (SD), agarose beads, and spray freeze-drying (SFD). Powder properties and physical stability were determined using particle size analysis, tap density measurement, scanning electron microscopy, optical microscopy, and moisture content analysis. Physical, chemical and biochemical stability of HBsAg was determined by dynamic light scattering, an enzyme immune assay, and immunogenicity in a mouse or hairless guinea pig model. Out of the four Powder-formation methods evaluated SFD outperformed other methods in the following considerations: good process efficiency, flexible scalability, and desirable particle characteristics for skin penetration. The stress posed by SFD appeared to be mild as HBsAg in the dry form retained its potency and immunogenicity. Notably, the mechanism of fast freezing by SFD actually promoted the preservation of HBsAg nanoparticle size, in good correlation with long-term biochemical stability. Among several Formulations screened, the Formulation containing 10 μg HBsAg in 1-mg Powder with a tertiary mixture of trehalose, mannitol, and dextran, exhibited excellent overall stability performance. In conclusion, HBsAg dry Powder Formulations suitable for EPI were successfully prepared using SFD. Further, a systematic Formulation development strategy allowed the development and optimization of an HBsAg dry Powder Formulation, demonstrating excellent long-term physical, biochemical, and immunological stability.
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influenza vaccine Powder Formulation development spray freeze drying and stability evaluation
Journal of Pharmaceutical Sciences, 2004Co-Authors: Mahmoud Ameri, Lendon G Payne, Dexiang ChenAbstract:Abstract The purpose of this study was to develop a spray‐freeze‐drying (SFD) process for preparing an influenza vaccine dry Powder Formulation suitable for epidermal Powder immunization. After preFormulation of two types of flu vaccines, their dry‐Powder Formulations were prepared by SFD. Powder properties and physical stability were determined using particle size analysis, tap density measurement, scanning electron microscopy, optical microscopy, and moisture content analysis. Chemical and biochemical stability of vaccine antigens was determined by sodium dodecyl sulfate–polyacrylamide gel electrophoresis, single radial immunodiffusion assay, and in vivo immunogenicity in a mouse model. We demonstrated that SFD could produce high‐density particles—a critical parameter for effective skin penetration. From the stability perspective, the stress posed by SFD was mild because the antigen in the dry Powder retained its stability, potency, and immunogenicity. Among several Formulations screened, we noted that Formulation composition has a significant role in the Powder's long‐term physical and biochemical stability. One Formulation, in particular, containing sub‐unit vaccine (45 μg of antigen in 1 mg of Powder) with a tertiary mixture of trehalose, mannitol, and dextran, exhibited excellent overall stability, including acceptable biochemical stability after being exposed to a highly humid environment. After all, we have not only demonstrated the suitability of SFD to prepare Powders for epidermal Powder immunization but also developed a systematic Formulation development strategy that allowed the optimization of an influenza vaccine dry Powder Formulation. More important, this study led to the selection of a Formulation system that had been successfully tested in a human clinical study. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1912–1923, 2004
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Optimization of an Alum-Adsorbed Vaccine Powder Formulation for Epidermal Powder Immunization
Pharmaceutical Research, 2003Co-Authors: Mahmoud Ameri, Lendon G Payne, Cindy L. Zuleger, Jorge E. Osorio, Dexiang ChenAbstract:Purpose . To develop stable and effective aluminum salt (alum)-adsorbed vaccine Powder Formulations for epidermal Powder immunization (EPI) via a spray freeze-drying (SFD) process. Methods . Powder properties were determined using particle size analysis, tap density, and scanning electron microscopy. Alum coagulation was monitored via optical microscopy and particle sedimentation. Protein analysis was determined by the BCA protein assay, SDS-PAGE, and an enzyme immunoassay. In vivo immunogenicity and skin reactogenicity were performed on hairless guinea pigs and pigs, respectively. Results . SFD of hepatitis B surface antigen (HBsAg) adsorbed to aluminum hydroxide or aluminum phosphate using an excipient combination of trehalose/mannitol/dextran produced vaccine Powders of dense particles and satisfactory Powder flowability and hygroscopicity. This Formulation also offered excellent long-term stability to the Powder and the antigen. The two most important factors influencing alum particle coagulation are the freezing rate and the concentration of aluminum in the liquid Formulation for SFD. The SFD vaccines, when delivered to hairless guinea pigs by EPI or injected intramuscularly after reconstitution, were as immunogenic as the original liquid vaccine. A further study showed that EPI with SFD alum-adsorbed diphtheria-tetanus toxoid vaccine was well tolerated, whereas needle injection of the liquid Formulation caused persistent granuloma. Conclusions . Stabilization of alum-adsorbed vaccine by SFD has important implications in extending vaccination to areas lacking a cold chain for transportation and storage and may also accelerate the development of new immunization technologies such as EPI.
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optimization of an alum adsorbed vaccine Powder Formulation for epidermal Powder immunization
Pharmaceutical Research, 2003Co-Authors: Mahmoud Ameri, Lendon G Payne, Cindy L. Zuleger, Jorge E. Osorio, Dexiang ChenAbstract:Purpose. To develop stable and effective aluminum salt (alum)-adsorbed vaccine Powder Formulations for epidermal Powder immunization (EPI) via a spray freeze-drying (SFD) process.
Satoshi Shimizu - One of the best experts on this subject based on the ideXlab platform.
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transcatheter arterial infusion chemotherapy with a fine Powder Formulation of cisplatin for advanced hepatocellular carcinoma refractory to transcatheter arterial chemoembolization
Japanese Journal of Clinical Oncology, 2011Co-Authors: Satoru Iwasa, Masafumi Ikeda, Takuji Okusaka, Hideki Ueno, Chigusa Morizane, Kohei Nakachi, Shuichi Mitsunaga, Shunsuke Kondo, Atsushi Hagihara, Satoshi ShimizuAbstract:OBJECTIVE: The aim of this study was to assess the safety and efficacy of transcatheter arterial infusion chemotherapy using a fine-Powder Formulation of cisplatin for patients with advanced hepatocellular carcinoma refractory to transcatheter arterial chemoembolization. METHODS: We retrospectively examined the data of 84 consecutive patients with transcatheter arterial chemoembolization-refractory hepatocellular carcinoma who underwent transcatheter arterial infusion chemotherapy with a fine-Powder Formulation of cisplatin. Cisplatin was administered at the dose of 65 mg/m(2) into the feeding artery of the hepatocellular carcinoma. The treatment was repeated every 4-6 weeks, until the appearance of evidence of tumor progression or of unacceptable toxicity. RESULTS: Of the 84 patients, one patient (1.2%) showed complete response and two patients (2.4%) showed partial response, representing an overall response rate of 3.6% (95% confidence interval, 0.7-10.1). Of the remaining, 38 patients (45.2%) showed stable disease and 41 (48.8%) showed progressive disease. The median overall survival, 1-year survival rate and median progression-free survival in the entire subject population were 7.1 months, 27% and 1.7 months, respectively. Major Grade 3 or 4 adverse events included thrombocytopenia in 12 patients (14%) and elevation of the serum aspartate aminotransferase in 33 patients (39%). The gastrointestinal toxicities were mild and reversible. CONCLUSIONS: Transcatheter arterial infusion chemotherapy using a fine-Powder Formulation of cisplatin appears to have only modest activity, although the toxicity was also only mild, in patients with transcatheter arterial chemoembolization-refractory hepatocellular carcinoma.
Hakkim Chan - One of the best experts on this subject based on the ideXlab platform.
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high resolution nanoscale probing of bacteriophages in an inhalable dry Powder Formulation for pulmonary infections
Analytical Chemistry, 2019Co-Authors: Dipesh Khanal, Hakkim Chan, Rachel Yoon Kyung Chang, Sandra Morales, Wojciech ChrzanowskiAbstract:Use of Powder phage Formulations for the treatment of multiple-drug-resistant pulmonary infections is gaining attention. To achieve therapeutic benefits, it is critical for phages to remain stable in the Formulation. Assessment of phage stability relies on plaque assay (bioactivity), which requires Powder samples to be reconstituted in liquid. The purpose of this study was to develop an innovative approach using photothermal-induced resonance-enhanced atomic force microscopy infrared spectroscopy (AFM-IR) to assess the presence of phages and investigate their protein conformation in the solid state. Staphylococcal phage S83 was spray-dried with lactose and sodium stearate using spray-drying. The phage Powder recrystallized at 60% relative humidity (RH), so it was stored and handled below this RH. For the AFM-IR measurements, spray-dried Staphylococcal phage Sa83 Powder was embedded in resin, followed by microtome sectioning. AFM-IR spectra collected from different regions within the microtomed sections re...
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using two fluid nozzle for spray freeze drying to produce porous Powder Formulation of naked sirna for inhalation
International Journal of Pharmaceutics, 2018Co-Authors: Wanling Liang, Michael Y T Chow, Shing Fung Chow, Hakkim Chan, Philip Chi Lip KwokAbstract:Abstract Spray freeze drying is an attractive technology to produce Powder Formulation for inhalation. It can be used to generate large porous particles which tend to aerosolize efficiently and do not aggregate readily. It also avoids material to be exposed to elevated temperature. In this study, we reported the use of two-fluid nozzle to produce spray freeze dried Powder of small interfering RNA (siRNA). The effect of atomization gas flow rate and liquid feed rate were inspected initially using herring sperm DNA (hsDNA) as nucleic acid model. The atomization gas flow rate was found to have a major impact on the aerosol properties. The higher the atomization gas flow rate, the smaller the particle size, the higher the fine particle fraction (FPF). In contrast, the liquid feed rate had very minor effect. Subsequently, spray freeze dried siRNA Powder was produced at various atomization gas flow rates. The particles produced were highly porous as examined with the scanning electron microscopy, and the structural integrity of the siRNA was demonstrated with gel electrophoresis. The gene-silencing effect of the siRNA was also successfully preserved in vitro. The best performing siRNA Formulation was prepared at the highest atomization gas flow rate investigated with a moderate FPF of 30%. However, this was significantly lower than that obtained with the corresponding hsDNA counterparts (FPF ∼57%). A direct comparison between the hsDNA and siRNA Formulations revealed that the former exhibited a lower density, hence a smaller aerodynamic diameter despite similar geometric size.
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inhaled Powder Formulation of naked sirna using spray drying technology with l leucine as dispersion enhancer
International Journal of Pharmaceutics, 2017Co-Authors: Michael Y T Chow, Hakkim Chan, Philip Chi Lip Kwok, Fiona F K LoAbstract:Abstract Pulmonary delivery of short interfering RNA (siRNA) has been widely studied in both animal and clinical studies to treat various respiratory diseases by gene silencing through RNA interference. Some of these studies showed that the administration of naked siRNA (without the use of any delivery vectors) could achieve satisfactory gene silencing effect, a unique feature to pulmonary delivery. Liquid aerosols were mostly used with very limited studies on the use of Powder aerosols for siRNA. In this study, siRNA was co-spray dried with mannitol and l -leucine, the latter being a dispersion enhancer. To the best of our knowledge, this is the first time that siRNA in its naked form was formulated into an inhalable dry Powder using spray drying technology. The aerosol performance of the Powder was evaluated by Next Generation Impactor (NGI). The presence of l -leucine in the Formulation could improve the aerosolization of siRNA-containing Powders. Results from the X-ray photoelectron spectroscopy (XPS) suggested that l -leucine was enriched on the particle surface and promote Powder dispersion. Among the different siRNA Formulations being examined, the one that contained 50% w/w of l -leucine exhibited the best aerodynamic performance, with a high emitted fraction (EF) of around 80% and a modest fine particle fraction (FPF) of 45%. Importantly, the integrity of siRNA was successfully retained as evaluated by gel retardation assay and high performance liquid chromatography (HPLC).