Systemic delivery of bictegravir and tenofovir alafenamide using dissolving microneedles for HIV preexposure prophylaxis

Chunyang Zhang, Yu Wu, Aaron R.J. Hutton, Akmal Hidayat Bin Sabri, James J. Hobson, Alison C. Savage, Helen O McCarthy, Alejandro J. Paredes, Andrew Owen, Steve Rannard, Ryan F. Donnelly

Research output: Contribution to journalArticlepeer-review

Abstract

Human immunodeficiency virus (HIV) continues to pose a serious threat to global health. Oral preexposure prophylaxis (PrEP), considered highly effective for HIV prevention, is the utilisation of antiretroviral (ARV) drugs before HIV exposure in high-risk uninfected individuals. However, ARV drugs are associated with poor patient compliance and pill fatigue due to their daily oral dosing. Therefore, an alternative strategy for drug delivery is required. In this work, two dissolving microneedle patches (MNs) containing either bictegravir (BIC) or tenofovir alafenamide (TAF) solid drug nanoparticles (SDNs) were developed for systemic delivery of a novel ARV regimen for potential HIV prevention. According to ex vivo skin deposition studies, approximately 11 % and 50 % of BIC and TAF was delivered using dissolving MNs, respectively. Pharmacokinetic studies in Sprague Dawley rats demonstrated that BIC MNs achieved a long-acting release profile, maintaining the relative plasma concentration above the 95 % inhibitory concentration (IC ) for 3 weeks. For TAF MNs, a rapid release of drug and metabolism of TAF into TFV were obtained from the plasma samples. This work has shown that the proposed transdermal drug delivery platform could be potentially used as an alternative method to systemically deliver ARV drugs for HIV PrEP.
Original languageEnglish
Article number124317
Pages (from-to)1-10
Number of pages10
JournalInternational journal of pharmaceutics
Volume660
Early online date6 Jun 2024
DOIs
Publication statusPublished (in print/issue) - 20 Jul 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Data Access Statement

Data will be made available on request.

Keywords

  • Human immunodeficiency virus
  • Bictegravir
  • Tenofovir alafenamide
  • Microneedles
  • Nanoparticles

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