Etravirine-loaded dissolving microneedle arrays for long-acting delivery

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, potentiallycontaminated 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.

Automated summary

The development of long-acting HIV therapy using dissolving microneedles loaded with etravirine nanosuspension shows potential for improving patient adherence through self-administration. Studies demonstrate higher deposition and efficacy compared to traditional intravenous solutions, suggesting promise for the future of HIV treatment.