Formulation of antiretroviral nanocrystals and development into a microneedle delivery system for potential treatment of HIV-associated neurocognitive disorder (HAND)

HIV/AIDS remains a major global public health issue. While antiretroviral therapy is effective at reducing the viral load in the blood, up to 50% of those with HIV suffer from some degree of HIV-associated neurocognitive disorder, due to the presence of the blood-brain barrier restricting drugs from crossing into the central nervous system and treating the viral reservoir there. One way to circumvent this is the nose-to-brain pathway. This pathway can also be accessed via a facial intradermal injection. Certain parameters can increase delivery via this route, including using nanoparticles with a positive zeta potential and an effective diameter of 200 nm or less. Microneedle arrays offer a minimally invasive, pain-free alternative to traditional hypodermic injections. This study shows the formulation of nanocrystals of both rilpivirine (RPV) and cabotegravir, followed by incorpo-ration into separate microneedle delivery systems for application to either side of the face. Following an in vivo study in rats, delivery to the brain was seen for both drugs. For RPV, a Cmax was seen at 21 days of 619.17 +/- 73.32 ng/g, above that of recognised plasma IC90 levels, and potentially therapeutically relevant levels were maintained for 28 days. For CAB, a Cmax was seen at 28 days of 478.31 +/- 320.86 ng/g, and while below rec-ognised 4IC90 levels, does indicate that therapeutically relevant levels could be achieved by manipulating final microaaray patch size in humans.

Automated summary

HIV/AIDS remains a global public health issue, which can lead to HIV-associated neurocognitive disorder due to the restriction of drugs crossing the blood-brain barrier. The nose-to-brain pathway and facial intradermal injection provide potential solutions to deliver drugs into the central nervous system. Nanoparticles and microneedle arrays are effective in increasing drug delivery via these routes.