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Title: Dissolving microneedle arrays for enhanced transcutaneous delivery of a model antigen
Author: Alzahrani, Sharifah Yahya
ISNI:       0000 0004 5353 4444
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2014
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Vaccination remains the most important approach to offering protection from infectious diseases. However, using needles and syringes for vaccine administration continues to be a matter of concern, especially in developing countries. Re-use of needles, needle stick injuries and improper disposal of needles in these regions of the world increase the risk of spreading blood-borne pathogens among health care workers, patients and the wider community. The concerns about the safe vaccination practice have led to an intensive effort to develop safe delivery methods for vaccines and replace hypodermic injections. The opportunity to develop a safe and effective method of vaccination using a minimally invasive method is becoming real. The most promising approaches is microneedle (MN) array which has proven to be a safe and cost effective method for vaccination. The current thesis was focus on dissolvable MNs fabricated from 20%w/w poly(methyl vinyl ether/maleic acid) loaded with a model antigen, ovalbumin (OVA). Various experiments were carried out during this thesis to investigate the feasibility and efficacy of using MNs for vaccine delivery. The in vitro studies showed that MNs loaded with OVA were strong enough to avoid breaking under high compression force. The integrity of the primary and secondary structure of OVA loaded into MN arrays successfully ensured. Further, MNs enhanced the release of OVA into the skin compared to passive permeation. In in vivo studies, the OVA released from the MNs' matrix upon insertion into mouse skin targeted dendrite cells (DCs). This thesis showed that av A was engulfed by DCs, processed and migrated to the lymph nodes. Consequently, the processed antigen encountered naive T cells, which led to initiation of robust humoral and cellular immune responses indicated by production of IgG, IgG 1, IgG2a, IFN-γ and IL-4. Interestingly, the PMVE/MA copolymer used to fabricate MNs seems to have adjuvant effects, indicated by the higher IgG level of mice immunized using MNs fabricated from PMVE/MA loaded with OVA compared with MNs fabricated from PMVE/MA and loaded with OVA plus adjuvant imiquimod.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available