2-Hydroxypropyl-β-cyclodextrin-enhanced pharmacokinetics of cabotegravir from a nanofluidic implant for HIV pre-exposure prophylaxis

J Control Release. 2019 Jul 28:306:89-96. doi: 10.1016/j.jconrel.2019.05.037. Epub 2019 May 25.


Preexposure prophylaxis (PrEP) with antiretrovirals (ARV) can prevent human immunodeficiency virus (HIV) transmission, but its efficacy is highly dependent on strict patient adherence to daily dosing regimen. Long-acting (LA) ARV formulations or delivery systems that reduce dosing frequency may increase adherence and thus PrEP efficacy. While cabotegravir (CAB) long-acting injectable (CAB LA), an integrase strand transfer inhibitor (INSTI), reduces dosing frequency to bimonthly injections, variable pharmacokinetics (PK) between patients and various adverse reactions necessitate improvement in delivery methods. Here we developed a subcutaneously implantable nanofluidic device for the sustained delivery of CAB formulated with 2-hydroxypropyl-β-cyclodextrin (βCAB) and examined the pharmacokinetics (PK) in Sprague-Dawley rats for 3 months in comparison to CAB. Our study demonstrated βCAB treatment group maintained clinically-relevant plasma CAB concentrations 2 times above the protein-adjusted concentration that inhibits viral replication by 90% (2 × PA-IC90) and drug penetration into tissues relevant to HIV-1 transmission. Further, we successfully fitted plasma CAB concentrations into a PK model (R2 = 0.9999) and determined CAB apparent elimination half-life of 47 days. Overall, our data shows the potential of sustained release of βCAB via a nanofluidic implant for long-term PrEP delivery, warranting further investigation for efficacy against HIV infections.

Keywords: Cabotegravir; Formulation; HIV; Implant; PrEP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin / administration & dosage*
  • Animals
  • Anti-HIV Agents / pharmacokinetics*
  • Drug Delivery Systems / adverse effects
  • Drug Delivery Systems / instrumentation*
  • HIV Infections / prevention & control*
  • Male
  • Pre-Exposure Prophylaxis*
  • Pyridones / administration & dosage
  • Pyridones / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley


  • Anti-HIV Agents
  • Pyridones
  • 2-Hydroxypropyl-beta-cyclodextrin
  • cabotegravir