Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.706993
Title: Pharmaceutical engineering of microneedle-mediated intradermal nanoparticle delivery device : potential for lymphatic targeting
Author: Kennedy, Joakim
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2016
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Abstract:
Microneedles (MNs) are minimally invasive drug delivery devices that can be used for transdermal drug delivery (TDD). They have the potential to enhance drug delivery for therapeutic agents which are currently difficult to deliver, costly, or cause a wide range of side effects. The therapeutic agent must normally overcome the highly hydrophobic barrier of the skin’s outermost layer, the stratum corneum (s.c.), in order to be delivered transdermally. MNs have a height of 50 m to 1500 m and overcome the barrier by penetrating the s.c. and creating aqueous pores. They can be fabricated from different materials, such as silicon, metal, glass, sugars, and polymers. Dissolving polymeric MNs are used to penetrate the s.c. and release the drug incorporated in the polymeric matrix into the epidermis when they dissolve by taking up skin interstitial fluid (ISF). This means that when nanoparticles (NPs) are delivered using dissolving MNs, the amount delivered is dependent upon the amount localized in the needle portion of the array. The present study developed and characterized dissolving MNs using a novel two-step process which improves the loading distribution of the therapeutic agent in the needle portion of the array. The two-step process fabricates the needles and the baseplate individually, allowing both to be fabricated from different for- mulations and optimized separately. The MNs were loaded with a model protein, ovalbumin (OVA), and poly(lactic-co-glycolide acid) (PLGA) NPs. When the loading distribution was measured for the NPs, it was found that about 80% of the NPs were localized in the needles. This is almost double the localization compared to arrays using the standard fabrication method. The MNs loaded with NPs were used in an in vivo mouse model. The NPs were successfully delivered into the skin of the mice and were detected in the draining lymph nodes. This showed that the developed TDD device can be used for targeted delivery of the lymphatic system. This study was overall successful in engineering a MN-mediated intradermal NP delivery device that can be used to target the lymphatic system.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.706993  DOI: Not available
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