Journal
PHARMACEUTICAL RESEARCH
Volume 40, Issue 7, Pages 1673-1696Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-022-03408-6
Keywords
AIDS; acquired immune deficiency syndrome; CAB; cabotegravir; HIV; human immunodeficiency virus; MAP; microarray patch; RPV; rilpivirine
Ask authors/readers for more resources
This study evaluates the intradermal delivery of long-acting injectable nanosuspensions of RPV LA and CAB LA using self-disabling dissolving microarray patches. The results show that these patches can maintain therapeutically relevant plasma concentrations for an extended period, making them a potential option to improve adherence in the paediatric population.
Purpose Whilst significant progress has been made to defeat HIV infection, the efficacy of antiretroviral (ARV) therapy in the paediatric population is often hindered by poor adherence. Currently, two long-acting (LA) intramuscular injectable nanosuspensions of rilpivirine (RPV) and cabotegravir (CAB) are in clinical development for paediatric populations. However, administration requires access to healthcare resources, is painful, and can result in needle-stick injuries to the end user. To overcome these barriers, this proof-of-concept study was developed to evaluate the intradermal delivery of RPV LA and CAB LA via self-disabling dissolving microarray patches (MAPs). Methods Dissolving MAPs of two conformations, a conventional pyramidal and a bilayer design, were formulated, with various nanosuspensions of RPV and CAB incorporated within the respective MAP matrix. MAPs were mechanically robust and were capable of penetrating ex vivo skin with intradermal ARV deposition. Results In a single-dose in vivo study in rats, all ARV MAPs demonstrated sustained release profiles, with therapeutically relevant plasma concentrations of RPV and CAB detected to at least 63 and 28 d, respectively. In a multi-dose in vivo study, repeated MAP applications at 14-d intervals maintained therapeutically relevant plasma concentrations throughout the duration of the study. Conclusions These results illustrate the potential of the platform to repeatedly maintain plasma concentrations for RPV and CAB. As such, these MAPs could represent a viable option to improve adherence in the paediatric population, one that is capable of being painlessly administered in the comfort of the patient's own home on a biweekly or less frequent basis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available