File Download
Supplementary
-
Citations:
- Appears in Collections:
postgraduate thesis: Development of Zein nanoparticles for nucleic acids delivery
Title | Development of Zein nanoparticles for nucleic acids delivery |
---|---|
Authors | |
Issue Date | 2017 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Chen, S. [陳松峰]. (2017). Development of Zein nanoparticles for nucleic acids delivery. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. |
Abstract | Gene therapy refers to introducing exogenous nucleic acids into human body with the attempt to alter the gene expression for the treatment of human diseases. It has provided a promising approach for the treatment of a wide range of diseases including cancer, infectious diseases and genetic diseases. However, the anionic and hydrophilic nature rendering naked nucleic acids unable to enter cytoplasm or nuclei. Moreover, enzymes like nuclease is capable to degrade nucleic acids before they can exert their effects. To overcome these obstacles, proper delivery vectors are essential when delivering therapeutic nucleic acids into cells. Compared with viral vectors which are efficient in transduction, non-viral vectors show potential advantages including low immunogenicity and high nucleic acids capacity. Zein is a kind of prolamines derived from corn, which is regarded as a potential material for the development of drug delivery systems due to multiple advantages especially its biocompatibility and biodegradability. Among various zein-based carriers, zein nanoparticles have been attached high importance due to their abilities to improve drug loading and delivery. Additionally, zein nanoparticles modifications with different purposes are possible. In this study, zein nanoparticles (Z-NPs) were fabricated by means of anti-solvent method. Sodium caseinate (CAS)-stabilized zein nanoparticles (ZC-NPs) and protamine-coated zein nanoparticles (ZP-NPs) were both investigated. DNA and small interfering RNA (siRNA) were loaded into ZP-NPs. The particle sizes of the nanoparticles prepared ranged from 100 nm to 300 nm. The zeta potential could be reversed into positive by protamine coating. When loaded with DNA at high DNA to protamine mass ratio (2:1), the positive charge of the nanoparticles could be reduced. Different cytotoxicity could be observed among different nanoparticles. Increasing the concentration of ZP-NPs could result in a reduced cell viability. Flow cytometry indicated a high cellular uptake of siRNA loaded nanoparticles but the uptake of DNA loaded nanoparticles was low. No DNA or siRNA transfection effect could be observed which could be due to a poor intracellular delivery or degradation of nucleic acids. Further study on optimizing this drug delivery system need to be conducted to improve transfection efficiency.
|
Degree | Master of Medical Sciences |
Subject | Nucleic acids Drug delivery systems Nanoparticles |
Dept/Program | Pharmacology and Pharmacy |
Persistent Identifier | http://hdl.handle.net/10722/251350 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chen, Songfeng | - |
dc.contributor.author | 陳松峰 | - |
dc.date.accessioned | 2018-02-27T09:53:44Z | - |
dc.date.available | 2018-02-27T09:53:44Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Chen, S. [陳松峰]. (2017). Development of Zein nanoparticles for nucleic acids delivery. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. | - |
dc.identifier.uri | http://hdl.handle.net/10722/251350 | - |
dc.description.abstract | Gene therapy refers to introducing exogenous nucleic acids into human body with the attempt to alter the gene expression for the treatment of human diseases. It has provided a promising approach for the treatment of a wide range of diseases including cancer, infectious diseases and genetic diseases. However, the anionic and hydrophilic nature rendering naked nucleic acids unable to enter cytoplasm or nuclei. Moreover, enzymes like nuclease is capable to degrade nucleic acids before they can exert their effects. To overcome these obstacles, proper delivery vectors are essential when delivering therapeutic nucleic acids into cells. Compared with viral vectors which are efficient in transduction, non-viral vectors show potential advantages including low immunogenicity and high nucleic acids capacity. Zein is a kind of prolamines derived from corn, which is regarded as a potential material for the development of drug delivery systems due to multiple advantages especially its biocompatibility and biodegradability. Among various zein-based carriers, zein nanoparticles have been attached high importance due to their abilities to improve drug loading and delivery. Additionally, zein nanoparticles modifications with different purposes are possible. In this study, zein nanoparticles (Z-NPs) were fabricated by means of anti-solvent method. Sodium caseinate (CAS)-stabilized zein nanoparticles (ZC-NPs) and protamine-coated zein nanoparticles (ZP-NPs) were both investigated. DNA and small interfering RNA (siRNA) were loaded into ZP-NPs. The particle sizes of the nanoparticles prepared ranged from 100 nm to 300 nm. The zeta potential could be reversed into positive by protamine coating. When loaded with DNA at high DNA to protamine mass ratio (2:1), the positive charge of the nanoparticles could be reduced. Different cytotoxicity could be observed among different nanoparticles. Increasing the concentration of ZP-NPs could result in a reduced cell viability. Flow cytometry indicated a high cellular uptake of siRNA loaded nanoparticles but the uptake of DNA loaded nanoparticles was low. No DNA or siRNA transfection effect could be observed which could be due to a poor intracellular delivery or degradation of nucleic acids. Further study on optimizing this drug delivery system need to be conducted to improve transfection efficiency. | - |
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 | Drug delivery systems | - |
dc.subject.lcsh | Nanoparticles | - |
dc.title | Development of Zein nanoparticles for nucleic acids delivery | - |
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_991043983766703414 | - |
dc.date.hkucongregation | 2017 | - |
dc.identifier.mmsid | 991043983766703414 | - |