Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.706298
Title: Microneedle-mediated transdermal drug delivery of biotherapeutic macromolecules
Author: Courtenay, Aaron John
ISNI:       0000 0004 6056 8124
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2016
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
Abstract:
In the last 20 years biotherapeutic macromolecules have become the fastest growing sector within pharmaceutical industry. Their development, facilitated by the introduction of advanced molecular engineering techniques, has led to improved treatment options for patients with autoimmune conditions, various cancer types, and infectious disease. The complex molecular structure of these drugs render them susceptible to degradation and, as a result, many commercially available products are suitable for parenteral drug delivery only. Subsequently, the hypodermic needle and syringe has remained the device of choice for biotherapeutic delivery, despite the many drawbacks associated with this method. Transdermal delivery has been an attractive alternative for many pharmaceutical formulators. However, few drugs possess the appropriate physicochemical properties required for crossing the human skin barrier. Microneedle (MN) technology combines micro-engineering and material sciences to fabricate micron scale projections manufactured onto a platform. That, when pressed against the skin, create aqueous apertures allowing drug delivery directly into the dermal tissue. This thesis explores the development of polymeric MN-based drug delivery systems, capable of facilitating intradermal and transdermal passage of biotherapeutic macromolecules. The model protein ovalbumin was incorporated into polymeric MN systems using commonly employed industrial manufacturing techniques and sterility was successfully demonstrated. Further these MN platforms were evaluated for intradermal delivery in vivo, highlighting the potential adjuvant effects of Gantrez® S-97. Subsequently, through industrial collaboration with market leading transdermal manufacturing company, Lohmann Therapie Systeme AG, the commercially available vaccine Pentavac® was successfully incorporated into dissolving MN arrays. This study has provided significant learnings for both academia and industrial partners, in relation to industrial manufacture of MN and biotherapeutic macromolecules. Finally, polymeric MN platforms were evaluated in vitro and in vivo for transdermal delivery of a therapeutically relevant monoclonal antibody, bevacizumab. This thesis provides significant evidence to support polymeric MN arrays, as minimally invasive intradermal and transdermal delivery platforms of biotherapeutic macromolecules. Focused input from key stakeholders, including: academia, industry, regulators, healthcare professionals and patients will be needed to ensure successful MN commercialisation
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.706298  DOI: Not available
Share: