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postgraduate thesis: Development of Zein nanoparticles for nucleic acids delivery

TitleDevelopment of Zein nanoparticles for nucleic acids delivery
Authors
Issue Date2017
PublisherThe 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.
AbstractGene 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.
DegreeMaster of Medical Sciences
SubjectNucleic acids
Drug delivery systems
Nanoparticles
Dept/ProgramPharmacology and Pharmacy
Persistent Identifierhttp://hdl.handle.net/10722/251350

 

DC FieldValueLanguage
dc.contributor.authorChen, Songfeng-
dc.contributor.author陳松峰-
dc.date.accessioned2018-02-27T09:53:44Z-
dc.date.available2018-02-27T09:53:44Z-
dc.date.issued2017-
dc.identifier.citationChen, S. [陳松峰]. (2017). Development of Zein nanoparticles for nucleic acids delivery. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR.-
dc.identifier.urihttp://hdl.handle.net/10722/251350-
dc.description.abstractGene 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.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subject.lcshNucleic acids-
dc.subject.lcshDrug delivery systems-
dc.subject.lcshNanoparticles-
dc.titleDevelopment of Zein nanoparticles for nucleic acids delivery-
dc.typePG_Thesis-
dc.description.thesisnameMaster of Medical Sciences-
dc.description.thesislevelMaster-
dc.description.thesisdisciplinePharmacology and Pharmacy-
dc.description.naturepublished_or_final_version-
dc.date.hkucongregation2017-
dc.identifier.mmsid991043983766703414-

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