# Ionic liquid-based nanoemulsion containing combination antiretroviral drugs forthe transdermal treatment of pediatric HIV infection

> **NIH NIH R21** · UNIVERSITY OF ARIZONA · 2024 · $216,759

## Abstract

PROJECT SUMMARY
The effective long-term management of HIV infection in pediatric patients faces a multitude of challenges such
as lack of age-appropriate pediatric formulations, high pill burden, unavailability of oral liquid formulations, poor
palatability of existing pediatric formulations, forgetfulness, and emerging independence in adolescents. These
challenges and psychosocial, behavioral, and socioeconomic barriers and health disparities have led to poor
adherence and only ~50% of children living with HIV are able to receive antiretroviral therapy. While the
intramuscular long-acting cabotegravir-rilpivirine (RPV) nanosuspension is highly effective in the long-term
management of HIV infections in adults and adolescents, there is a strong need to develop a non-invasive, room
temperature stable formulation that can allow for self-administration, high adherence and long-term HIV therapy
in children and adolescents affected with HIV. The non-invasive transdermal route is yet to be explored for the
delivery of potent second-generation antiretroviral drugs. Our preliminary study showed that dolutegravir (DTG)
has a great potential to be delivered as a transdermal formulation compared to cabotegravir whereas rilpivirine,
due to its high crystallinity and low aqueous and lipid solubility was not amenable for transdermal delivery. Ionic
liquids (ILs) are low-melting organic salts with a melting point < 100°C and pharmaceutically acceptable fatty
anionic permeation enhancers can be used to develop amphiphilic ILs with excellent drug solubilization capacity,
lipid solubility, and transdermal permeability. We hypothesize that rilpivirine (RPV) and generally regarded as
safe (GRAS) fatty anionic permeation enhancers can be assembled to develop amphiphilic RPV ILs with
excellent lipid solubility and solubilization capacity for DTG and that subsequent incorporation of RPV IL(s) and
DTG into transdermal lipid-based formulations such as nanoemulsion-based gel will improve transdermal
delivery of DTG-RPV combination. Our preliminary data show that a prototype nanoemulsion containing IL of
RPV (RPV docusate) and DTG combination showed significantly higher in vitro permeability of RPV and DTG
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-based gel formulations containing
various RPV ILs and DTG combination suitable for transdermal delivery. Aim 2 will focus on the pharmacokinetic
evaluation of transdermal nanoemulsion-based gel containing RPV IL and DTG combination in NSG mice to
establish the proof of concept. Aim 3 will evaluate the in vivo antiretroviral efficacy of nanoemulsion-based gel
containing RPV IL and DTG combination in a humanized mouse model of HIV infection. The successful
completion of this proposal will lead to the development of pharmaceutically viable formulations containing
combination antiretroviral drugs for effective l...

## Key facts

- **NIH application ID:** 10923305
- **Project number:** 1R21AI184072-01
- **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:** $216,759
- **Award type:** 1
- **Project period:** 2024-08-07 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10923305

## Citation

> US National Institutes of Health, RePORTER application 10923305, Ionic liquid-based nanoemulsion containing combination antiretroviral drugs forthe transdermal treatment of pediatric HIV infection (1R21AI184072-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10923305. Licensed CC0.

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