Etravirine-loaded dissolving microneedle arrays for long-acting delivery

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 165; pp. 41 - 51
• Main Authors: Rojekar, Satish, Vora, Lalitkumar K., Tekko, Ismaiel A., Volpe-Zanutto, Fabiana, McCarthy, Helen O., Vavia, Pradeep R., .Donnelly, Ryan F
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2021
• Subjects: Antiretroviral; Etravirine; HIV; Microarray patch; Microneedle; ETR; ARV; Antiretroviral; NNRTI; ETR LA NS; AIDS; PVP; DMNs; Microarray patch; HIV; Etravirine; PVA; MAP; Microneedle
• ISSN: 0939-6411; 1873-3441; 1873-3441
• DOI: 10.1016/j.ejpb.2021.04.024

[Display omitted] •Fabrication of dissolving polymeric microneedles (DMNs) for controlled drug delivery.•Etravirine (ETR) and etravirine nanosuspension (ETR NS) delivery by DMNs for sustained intradermal drug delivery.•ETR and ETR NS loaded DMNs maintained therapeutic plasma concentrations beyond 30 days in a preclinical in vivo study. A key challenge of HIV treatment with multiple antiretroviral drugs is patient adherence. Thus, there is an urgent need for long-acting depot systems for delivering drugs over an extended duration. Although the parenteral route is preferred for depot systems, it is associated with obvious drawbacks, such as painful injections, potentially-contaminated sharps waste, and the necessity of trained healthcare personnel for administration. Amongst a small number of alternatives in development microneedles are versatile delivery systems enabling systemic drug delivery and potentially improving patient adherence due to their capacity for self-administration. We have developed dissolving microneedle (DMNs) embedded with etravirine nanosuspension (ETR NS) as a long-acting HIV therapy to improve patient adherence. The ETR NS prepared by sonoprecipitation yielded particle sizes of 764 ± 96.2 nm, polydispersity indices of of 0.23 ± 0.02, and zeta potentials of −19.75 ± 0.55 mV. The DMNs loaded with ETR NS demonstrated 12.84 ± 1.33% ETR deposition in ex-vivo neonatal porcine skin after 6 h application. In in vivo rat pharmacokinetic studies, the Cmax exhibited by DMNs loaded with ETR powder and ETR NS were 158 ± 10 ng/mL and 177 ± 30 ng/mL, respectively. DMN groups revealed a higher t1/2, Tmax, and mean residence time compared to intravenous ETR solutions, suggesting the long-acting potential of etravirine delivered intradermally using DMNs.