File Download
Supplementary
-
Citations:
- Appears in Collections:
postgraduate thesis: Formulation of inhalable nucleic acids using spray freeze-drying technology
Title | Formulation of inhalable nucleic acids using spray freeze-drying technology |
---|---|
Authors | |
Issue Date | 2017 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Chan, Y. A. [陳育麟]. (2017). Formulation of inhalable nucleic acids using spray freeze-drying technology. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. |
Abstract | Inhaled nucleic acids have huge therapeutic potentials for treating respiratory diseases like infections and cancers, but many barriers have to be overcome before this technology can be translated from bench side to bedside. Formulation of inhaled nucleic acids is not well studied. Its safety and efficiency of powders by different technologies have been investigated in this decade. Spray freeze drying (SFD) is a technology which involves multi-step process to produce porous and inhalable particles with low cohesion between particles. With the desirable properties of SFD particle, SFD was employed in this project because of its great potential to convert the science to clinical practice. In this study, mannitol was used as bulking agent for determining the optimal condition of SFD and herring sperm DNA (hsDNA) was used as model of small nucleic acid therapeutics. Formulations produced by different feed rates (0.5, 1.0 and 2.0ml/min) and solute concentrations (2.0%, 3.0%, 5.0% and 10.0%w/v) were first evaluated. The median volumetric diameters of all formulations ranged from 10.33 μm to 17.18μm. SFD particles with higher solute concentration generally had higher volumetric diameters. For the aerodynamic performance evaluated by Next Generation Impactor (NGI), all SFD formulations exhibited satisfactory emitted fraction (EF, a measure of powder dispersibility) with an average value of 81.1%. Fine particle fraction (FPF, a measure of respirable fraction) from SFD particles with 2.0% to 5.0% solute concentration was relatively higher (ranged from 27% to 42%) and particles with 10.0% solute concentration had a lower average value (ranged from 15% to 23%). In addition, their structures as visualized by scanning electron microscopy (SEM) were more intact in higher solute concentrations (5.0% and 10.0% w/v) and particles were generally porous. No conclusive trend of SFD formulation was found across different feed rates. Feed rate of 2.0ml/min and 5.0% solute concentration were subsequently selected for further evaluation with hsDNA. The median volumetric diameters of different formulations (0.75%, 1.00% and 2.00%w/w hsDNA) ranged from 10.0 to 16.2μm. The diameters of SFD particles were decreasing with increasing concentration of hsDNA. The average EFs ranged from 86% to 93% which are similar to the result of mannitol powder without hsDNA. The FPFs ranged from 22% to 37% while the FPF without hsDNA was 36%. The SFD particles with hsDNA shared similar spherical morphology with SFD particles with mannitol only. With the desirable experimental results of SFD with hsDNA, other small nucleic acid therapeutics is suggested to investigate in future experiments.
|
Degree | Master of Medical Sciences |
Subject | Nucleic acids Inhalers Pharmaceutical technology Drying |
Dept/Program | Pharmacology and Pharmacy |
Persistent Identifier | http://hdl.handle.net/10722/251344 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chan, Yuk-lun, Alan | - |
dc.contributor.author | 陳育麟 | - |
dc.date.accessioned | 2018-02-27T09:53:43Z | - |
dc.date.available | 2018-02-27T09:53:43Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Chan, Y. A. [陳育麟]. (2017). Formulation of inhalable nucleic acids using spray freeze-drying technology. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. | - |
dc.identifier.uri | http://hdl.handle.net/10722/251344 | - |
dc.description.abstract | Inhaled nucleic acids have huge therapeutic potentials for treating respiratory diseases like infections and cancers, but many barriers have to be overcome before this technology can be translated from bench side to bedside. Formulation of inhaled nucleic acids is not well studied. Its safety and efficiency of powders by different technologies have been investigated in this decade. Spray freeze drying (SFD) is a technology which involves multi-step process to produce porous and inhalable particles with low cohesion between particles. With the desirable properties of SFD particle, SFD was employed in this project because of its great potential to convert the science to clinical practice. In this study, mannitol was used as bulking agent for determining the optimal condition of SFD and herring sperm DNA (hsDNA) was used as model of small nucleic acid therapeutics. Formulations produced by different feed rates (0.5, 1.0 and 2.0ml/min) and solute concentrations (2.0%, 3.0%, 5.0% and 10.0%w/v) were first evaluated. The median volumetric diameters of all formulations ranged from 10.33 μm to 17.18μm. SFD particles with higher solute concentration generally had higher volumetric diameters. For the aerodynamic performance evaluated by Next Generation Impactor (NGI), all SFD formulations exhibited satisfactory emitted fraction (EF, a measure of powder dispersibility) with an average value of 81.1%. Fine particle fraction (FPF, a measure of respirable fraction) from SFD particles with 2.0% to 5.0% solute concentration was relatively higher (ranged from 27% to 42%) and particles with 10.0% solute concentration had a lower average value (ranged from 15% to 23%). In addition, their structures as visualized by scanning electron microscopy (SEM) were more intact in higher solute concentrations (5.0% and 10.0% w/v) and particles were generally porous. No conclusive trend of SFD formulation was found across different feed rates. Feed rate of 2.0ml/min and 5.0% solute concentration were subsequently selected for further evaluation with hsDNA. The median volumetric diameters of different formulations (0.75%, 1.00% and 2.00%w/w hsDNA) ranged from 10.0 to 16.2μm. The diameters of SFD particles were decreasing with increasing concentration of hsDNA. The average EFs ranged from 86% to 93% which are similar to the result of mannitol powder without hsDNA. The FPFs ranged from 22% to 37% while the FPF without hsDNA was 36%. The SFD particles with hsDNA shared similar spherical morphology with SFD particles with mannitol only. With the desirable experimental results of SFD with hsDNA, other small nucleic acid therapeutics is suggested to investigate in future experiments. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject.lcsh | Nucleic acids | - |
dc.subject.lcsh | Inhalers | - |
dc.subject.lcsh | Pharmaceutical technology | - |
dc.subject.lcsh | Drying | - |
dc.title | Formulation of inhalable nucleic acids using spray freeze-drying technology | - |
dc.type | PG_Thesis | - |
dc.description.thesisname | Master of Medical Sciences | - |
dc.description.thesislevel | Master | - |
dc.description.thesisdiscipline | Pharmacology and Pharmacy | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.5353/th_991043983766803414 | - |
dc.date.hkucongregation | 2017 | - |
dc.identifier.mmsid | 991043983766803414 | - |