Novel bilayer microarray patch-assisted long-acting micro-depot cabotegravir intradermal delivery for HIV pre-exposure prophylaxis

Injectable long-acting cabotegravir (CAB LA) is effective and safe for pre-exposure HIV prophylaxis. It is recently approved for clinical use in those at high risk of contracting HIV. However, injections are invasive and access to trained healthcare personnel to administer CAB LA can be limited, especially in low-income countries (LICs). Herein, for the first time, the development of a bilayer microarray patch (MAP) with unique design and novel formulation as a potential alternative self-administrated intradermal delivery system for CAB is reported. The novel MAP has a high drug load (≈3 mg/0.5 cm² of CAB LA or its micronized sodium salt) and fast-dissolving tips (<30 min) and shows good mechanical properties and skin insertion capabilities. Importantly, in preclinical in vivo studies using Sprague Dawley rats, this MAP is able to implant the drug-loaded tips in the skin, forming micro-depots. Both drug forms are then released in a sustained manner, maintaining human therapeutic levels in the rats for one month after a single application. Weekly repeated MAP dosing in the rats showed the MAPs to be reproducible and well-tolerated. This bilayer MAP presents a promising minimally-invasive, self-administered, alternative delivery system for CAB for enhanced HIV prevention, especially in LICs.