Wen, JingyuanDuarah, Sanjukta2021-11-032021-11-032021https://hdl.handle.net/2292/57202Background: Microneedle (MN) technology is a promising technique that ensures effective drug delivery using multiple micron-sized needles. MNs made using biodegradable polymers degrade slowly in the skin after application and can provide sustained drug release for extended durations. Anti-inflammatory drugs are ideal candidates to be delivered using MNs. They are used for long-term therapy, which necessitates the need for patient compliant drug delivery systems that are less painful and have less impact on daily activities. Dexamethasone is a popular and highly potent anti-inflammatory drug, frequently used to treat a wide range of inflammatory disorders. However, the existing oral and injection modes of its delivery have several limitations. Therefore, this study aims to develop a biodegradable MN-based transdermal delivery system capable of sustained, safe and effective delivery of dexamethasone. Methods: Quality by Design (QbD) approach was applied for optimising the fabrication of dexamethasone-loaded MN arrays. The developed MN arrays were characterised for morphology, in vitro release profiles and stability. The skin permeation and deposition efficiencies were studied using ex vivo skin models. Cytotoxicity of the MNs was assessed using human dermal fibroblast cells and human keratinocytes. Finally, the in vivo anti-inflammatory efficacy was investigated using the carrageenan-induced rat paw edema model. Results and discussion: Two types of MNs were optimised and fabricated using different polymeric combinations. The developed MNs were sharp, with heights ranging between 800-900 μm, appropriate for transdermal delivery. The MN arrays did not exhibit any cytotoxic effects on the fibroblast and keratinocyte cells. Ex vivo studies confirmed the enhanced efficacy of MN-mediated skin permeation of dexamethasone compared to permeation achieved using DexP solution. This was further supported by the in vivo studies. The efficacy of the MN arrays to inhibit paw edema formation was comparable to that of intravenous dexamethasone injection and significantly greater than topical solution. The MN-treated rats also showed reduced inflammatory cell infiltration on histological examination and resulted in significant inhibitory effects against the inflammatory cytokines. Conclusion: This project has successfully demonstrated the safety and efficacy of MN arrays for transdermal delivery of dexamethasone. The potential of MN arrays to provide sustained release for a prolonged period can be effectively utilised for the long-term treatment of inflammatory disorders. The findings suggested that MN array could be a minimally invasive and patient compliant alternative to the existing means of dexamethasone delivery.Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htmhttp://creativecommons.org/licenses/by-nc-sa/3.0/nz/Thesis2021-09-27Copyright: The authorhttp://purl.org/eprint/accessRights/OpenAccessQ112563017