Design and evaluation of novel microencapsulation technologies to enhance delivery of Ciclosporin

dc.check.date10000-01-01
dc.check.embargoformatBoth hard copy thesis and e-thesisen
dc.check.entireThesisEntire Thesis Restricted
dc.check.infoIndefiniteen
dc.check.opt-outYesen
dc.check.reasonThis thesis contains third party copyrighted materials for which permission was not given for online useen
dc.contributor.advisorGriffin, Brendan T.en
dc.contributor.authorKeohane, Kieran
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2015-08-14T08:44:51Z
dc.date.issued2014
dc.date.submitted2014
dc.description.abstractDrug delivery systems influence the various processes of release, absorption, distribution and elimination of drug. Conventional delivery methods administer drug through the mouth, the skin, transmucosal areas, inhalation or injection. However, one of the current challenges is the lack of effective and targeted oral drug administration. Development of sophisticated strategies, such as micro- and nanotechnology that can integrate the design and synthesis of drug delivery systems in a one-step, scalable process is fundamental in advancing the limitations of conventional processing techniques. Thus, the objective of this thesis is to evaluate novel microencapsulation technologies in the production of size-specific and target-specific drug-loaded particles. The first part of this thesis describes the utility of PDMS and silicon microfluidic flow focusing devices (MFFDs) to produce PLGA-based microparticles. The formation of uniform droplets was dependent on the surface of PDMS remaining hydrophilic. However, the durability of PDMS was limited to no more than 1 hour before wetting of the microchannel walls with dichloromethane and subsequent swelling occurred. Critically, silicon MFFDs revealed very good solvent compatibility and was sufficiently robust to withstand elevated fluid flow rates. Silicon MFFDs facilitated experiments to run over days with continuous use and re-use of the device with a narrower microparticle size distribution, relative to conventional production techniques. The second part of this thesis demonstrates an alternative microencapsulation technology, SmPill® minispheres, to target CsA delivery to the colon. Characterisation of CsA release in vitro and in vivo was performed. By modulating the ethylcellulose:pectin coating thickness, release of CsA in-vivo was more effectively controlled compared to current commercial CsA formulations and demonstrated a linear in-vitro in-vivo relationship. Coated minispheres were shown to limit CsA release in the upper small intestine and enhance localised CsA delivery to the colon.en
dc.description.sponsorshipScience Foundation Ireland (SFI research cluster, Irish Drug Delivery Network, Grant 07/SRC/B1154)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationKeohane, K. 2014. Design and evaluation of novel microencapsulation technologies to enhance delivery of Ciclosporin. PhD Thesis, University College Cork.en
dc.identifier.urihttps://hdl.handle.net/10468/1907
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2014, Kieran Keohane.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectMicrofluidicsen
dc.subjectCiclosporin Aen
dc.subjectPLGAen
dc.subjectSmPill®en
dc.subjectColonic targetingen
dc.subjectControlled releaseen
dc.thesis.opt-outfalse
dc.titleDesign and evaluation of novel microencapsulation technologies to enhance delivery of Ciclosporinen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Medicine and Health)en
ucc.workflow.supervisorbrendan.griffin@ucc.ie
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