Development, characterisation and evaluation of sugar glass microneedles

Martin, Christopher 2012. Development, characterisation and evaluation of sugar glass microneedles. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Biodegradable microneedles (MNs) are currently being developed to painlessly facilitate the effective permeation of therapeutic substances across the skin barrier. As sugar glasses are utilised in nature to protect proteins and other delicate structures upon dehydration, such materials may be an appropriate substrate for the preparation of biodegradable MNs. The aim of this work was to investigate for the first time the feasibility of preparing biodegradable MNs from sugar glasses and to test their potential utility for drug delivery applications. Solid sugar products were fabricated from 32 different solutions containing a range of individual sugars and binary sugar combinations, utilising a low temperature dehydration methodology. Subsequently, a novel vacuum-forming micromoulding methodology was developed and optimised to produce sugar glass microneedle (SGMN) arrays from silicon master structures. The sugar materials and MN structures were characterised using a variety of microscopic, thermal and x-ray diffraction analyses. The ability of SGMNs to puncture human skin was assessed in an in vitro skin model, whilst SGMN facilitated drug delivery was investigated using modified static Franz-type diffusion cells. A range of model substances including methylene blue (MB) dye, ibuprofen sodium (IBU), sulforhodamine B (SRB), FITC-BSA and β-galactosidase (β-gal) were incorporated within SGMN arrays. Furthermore, novel SGMN adhesive patches containing SRB within the backing only were fabricated using silicone and acrylate adhesives. Long-term stability of SGMN arrays was assessed under a range of differing storage conditions. Initial characterisation studies suggested that non-crystalline sugar material was formed from anhydrous trehalose and sucrose (75:25 %w/w) sugar solutions. This finding was critical to future SGMN fabrication and incorporation of model substances within the material. Process optimisation led to fabrication of SGMNs with strong morphological fidelity to master structures, which reliably penetrated human skin to facilitate diffusion of MB dye. Furthermore, SGMNs were shown to dissolve rapidly and completely in human skin and deliver MB, IBU, SRB and FITC-BSA to the deeper skin layers. Diffusion study data suggested that SGMN arrays incorporating a range of model substances facilitated permeation across skin in a bolus delivery manner. Additionally, it was found that SGMN adhesive patches were able to control permeation of SRB, a model hydrophilic compound. Sugar glasses containing β-gal were shown to stabilise enzyme functionality at approximately 40 % of initial activity over a 3 month period when stored under desiccation. Elevated humidity and temperature storage was detrimental to SGMN morphology, with 10 % relative humidity at 20 °C being optimal for MN preservation. Overall, this study suggests the utility of SGMNs for the stable incorporation and effective intra- or trans-dermal delivery of a range of model substances, including hydrophilic and macromolecular molecules. Furthermore, it was shown that a novel SGMN adhesive patch may provide the capability to control drug release across skin. Sugar glasses demonstrated a stabilising effect upon a functional protein cargo, although it appeared that storage conditions had a strong influence upon physical SGMN stability.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Pharmacy
Subjects:	Q Science > Q Science (General) R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords:	Biodegradable; Sugar; Glass; Microneedle; Skin; Permeation
Date of First Compliant Deposit:	30 March 2016
Last Modified:	13 Sep 2023 13:34
URI:	https://orca.cardiff.ac.uk/id/eprint/32320

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