TY - JOUR
T1 - Formulation of antiretroviral nanocrystals and development into a microneedle delivery system for potential treatment of HIV-associated neurocognitive disorder (HAND)
AU - Abbate, Marco
AU - Ramöller, Inken K.
AU - Sabri, Akmal H.
AU - Paredes, Alejandro J.
AU - Hutton, Aaron
AU - McKenna, Peter E.
AU - Peng, Ke
AU - Hollett, Jessica A.
AU - McCarthy, Helen
AU - Donnelly, Ryan F.
PY - 2023/6/10
Y1 - 2023/6/10
N2 - 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 incorporation 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 recognised 4IC90 levels, does indicate that therapeutically relevant levels could be achieved by manipulating final microaaray patch size in humans.
AB - 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 incorporation 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 recognised 4IC90 levels, does indicate that therapeutically relevant levels could be achieved by manipulating final microaaray patch size in humans.
KW - Microneedle
KW - Rilpivrine
KW - Cabotegravir
KW - HIV-associated neurocognitive disorder
KW - HAND
KW - Blood-brain barrier
KW - Nanocrystal
UR - https://pure.qub.ac.uk/en/publications/f4423f78-4277-471c-bb1e-c4f9059fef32
U2 - 10.1016/j.ijpharm.2023.123005
DO - 10.1016/j.ijpharm.2023.123005
M3 - Article
C2 - 37142137
SN - 0378-5173
VL - 640
SP - 1
EP - 15
JO - International journal of pharmaceutics
JF - International journal of pharmaceutics
M1 - 123005
ER -