# Ionic liquid-based nanoemulsion containing combination antiretroviral drugs for the oral and transdermal treatment of HIV infection

> **NIH NIH R21** · UNIVERSITY OF ARIZONA · 2024 · $208,575

## Abstract

PROJECT SUMMARY
Two-drug regimen (2-DR) containing potent second-generation integrase inhibitor (INI) and non-nucleoside
reverse transcriptase inhibitor (NNRTI) are currently available as oral formulation (dolutegravir-rilpivirine) and
long-acting injectable nanosuspension (cabotegravir-rilpivirine) for HIV prophylaxis and therapy. Oral 2-DR tablet
(Juluca; dolutegravir-rilpivirine) is equally effective but with significantly lower adverse effects compared to the
three-drug regimen based on 2 NRTIs. However, dolutegravir (DTG) and rilpivirine (RPV) both have pH
dependent solubility, low oral bioavailability and long-term use of INI can lead to metabolic diseases including
diabetes. Given the need for lifelong administration of these drugs, strategies that can improve the oral
bioavailability of DTG and RPV are highly desirable for optimal drug utilization and to achieve a reduction in
therapeutic dose and dose-related side effects. While the intramuscular long-acting cabotegravir-RPV
nanosuspension is highly effective in the long-term management of HIV infections, there is a strong need to
develop a non-invasive, strategy that can allow for self-administration and long-term HIV therapy. The non-
invasive transdermal route is yet to be explored for the delivery of 2-DR containing INI and NNRTI. Ionic liquids
(ILs) are low-melting organic salts with a melting point < 100°C and pharmaceutically acceptable fatty cations
and/or anions can be used to develop amphiphilic ILs with excellent drug solubilization capacity.
Pharmaceutically acceptable cations and fatty anions can be assembled into amphiphilic ILs with excellent
biocompatibility and drug solubilization capabilities. We hypothesize that carnitine, a generally regarded as safe
(GRAS) cation and fatty anionic permeation enhancers with GRAS status can be assembled to develop
amphiphilic ILs with excellent solubilization capacity for hydrophobic drugs such as DTG and RPV and that
subsequent incorporation of these ILs into oral lipid-based formulations (LBFs) such as self-nanoemulsifying
systems (SNES) and transdermal LBFs such as nanoemulsion-based gel will improve oral and transdermal
delivery of DTG-RPV combination. Our preliminary data show that a co-processed mixture of DTG and RPV has
very high solubility (RPV: ~ 166 mg/g and DTG: 334 mg/ml) in amphiphilic carnitine IL (carnitine salcaprozate)
and carnitine salcaprozate containing DTG-RPV mixture showed significantly higher in vitro permeability through
skin mimicking Strat-M membrane compared to DTG-RPV suspension. Aim 1 will focus on the development,
characterization, and in vitro evaluation of nanoemulsion of carnitine ILs containing DTG-RPV combination
suitable for oral and transdermal delivery. Aim 2 will focus on the pharmacokinetic evaluation of oral and
transdermal lipid nanoformulations of carnitine IL containing DTG-RPV combination in healthy mice to establish
the proof of concept. The successful completion of this proposal will lea...

## Key facts

- **NIH application ID:** 10836933
- **Project number:** 1R21AI181603-01
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Abhijit A Date
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $208,575
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836933

## Citation

> US National Institutes of Health, RePORTER application 10836933, Ionic liquid-based nanoemulsion containing combination antiretroviral drugs for the oral and transdermal treatment of HIV infection (1R21AI181603-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10836933. Licensed CC0.

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