AbstractAcquired immunodeficiency syndrome (AIDS) is a chronic, potentially life-threatening condition caused by the human immunodeficiency virus (HIV), which affects approximately 36.7 million people worldwide. However, despite the advent of antiretroviral treatment (ART), poor adherence to daily oral dosing results in inadequate exposure to drugs to suppress viral replication and brings about virus resistance. The development of long-acting parenteral ARV formulations
provides the promise to overcome the challenges of non-adherence. Nevertheless, the proposed administration route via intramuscular (IM) injection poses significant challenges, especially in low-income countries. Microneedles (MNs) are innovative devices containing hundreds of microprojections which can be applied for minimally-invasive intradermal delivery of antiretroviral drugs (ARVs) into the skin by breaching the stratum corneum (SC). This Thesis explores the
development of the dissolving MN-mediated drug delivery system for intradermal delivery of the long-acting HIV drug bictegravir (BIC) for sustained release. BIC was formulated into nanosuspensions using wet media milling technique at a laboratory scale. BIC nanosuspensions were rationalised in terms of milling time, size of milling media and drug content. The rationalised nanosuspensions were lyophilised and incorporated into dissolving MNs. Apart from this, MNs
containing crude BIC were also manufactured. These prepared MNs were characterised according to height reduction, insertion ability, dissolution study and ex vivo skin deposition. To investigate the pharmacokinetic profile of the BIC delivered from a such dissolving MN platform, a Sprague-Dawley rat model was used. This drug delivery system has achieved a relevant plasma concentration for a period of 28 days. This Thesis provides the evidence concerning the
successfully intradermal delivery of BIC using this novel drug delivery system. To promote the commercialisation of the MN-based product, a variety of good manufacture practice (GMP) and quality control (QC) test need be well established and validated by the manufacturers.
Thesis is embargoed until 31 December 2027.
|Date of Award||Dec 2022|
|Supervisor||Ryan Donnelly (Supervisor) & Eneko Larrañeta (Supervisor)|
- Human immunodeficiency virus