AbstractIncreasing emergence of drugs with poor solubility poses significant challenges for the pharmaceutical industry. A variety of techniques can be used to help improve the solubility profile of these difficult-to-deliver compounds. Intradermal delivery of poorly soluble drugs involves the delivery of drugs into the skin to exert localised effects. However, relatively few drugs possess the necessary properties to passively traverse the skin and remain in the skin in a high level and long-acting way. Microneedles are a novel drug delivery technology that increase skin permeability by creating microscopic pores within the skin, thereby reducing the barrier to drug permeation. This thesis focuses on developing the novel polymeric microneedle systems to deliver poorly soluble molecules intradermally in a sustained manner.
In this thesis, amphotericin B, a model poorly soluble drug, was formulated using polymeric microneedle systems to achieve localised, long-acting intradermal delivery. Implantable microneedle systems and a dissolving microneedle system with reduced-size particles were developed to deliver amphotericin B. The biodegradable polymers poly(caprolactone) and poly(lactic-co-glycolic acid) were used as the matrices for implantable drug-containing tips. The water soluble polymers poly(vinyl pyrrolidone) and poly(vinyl alcohol) were used to form dissolving microneedle tips loaded with amphotericin B. These microneedle formulations were characterised in terms of drug content, mechanical properties, insertion capabilities, and importantly, ex vivo skin insertion and deposition. The rationalised formulations were taken into in vitro release studies and also antifungal examinations. In vivo studies were performed to demonstrate the long-acting effects and systemic exposure of the chosen formulations. This thesis provides significant evidence regarding the successful localised and long-acting delivery of amphotericin B, a model hydrophobic drug, using these novel approaches. These promising technologies could simplify administration of amphotericin B in particular, thus expanding access to antifungal therapies especially in developing countries. This work could readily be expanded to hydrophobic molecules in general. Future research should consider pharmacodynamic studies using suitable animal models. For commercialisation, input from key stakeholders, including academia, industry, regulators, healthcare professionals and patients will be required.
Thesis embargoed until 31 December 2026.
|Date of Award
|Ryan Donnelly (Supervisor) & Eneko Larrañeta (Supervisor)
- Intradermal drug delivery
- amphotericin B
- long-acting drug delivery