Transdermal delivery of enfuvirtide using hydrogel-forming and dissolving microneedle array patches with novel feedback systems

Despite its efficacy, the need for 90 mg subcutaneous injections twice daily has led to a high incidence (98%) of injection site reactions, often resulting in discontinuation. This thesis introduces advanced transdermal delivery methods, specifically hydrogel-forming microneedle array patches (HMAPs) and dissolving microneedle array patches (DMAPs), designed to deliver enfuvirtide painlessly through the skin and mitigate injection site reactions.The study first developed and validated methods for accurate enfuvirtide quantification, establishing HPLC-FLD and LC-MS protocols for both in vitro and in vivo analyses.

It then optimized HMAP formulations to achieve sustained delivery, identifying critical material attributes (CMAs) and critical process parameters (CPPs) using a quality by design (QbD) approach. These optimized HMAPs displayed effective drug release and mechanical strength, though adjustments were needed to match enfuvirtide’s rapid clearance from the bloodstream.A novel feedback system using color-changing DMAPs was also created to enhance administration accuracy.