# Ionic Liquids of tenofovir prodrugs for improved oral bioavailability and antiviral efficacy

> **NIH NIH R21** · UNIVERSITY OF ARIZONA · 2023 · $230,250

## Abstract

PROJECT SUMMARY
Tenofovir prodrugs, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide fumarate (TAF) are
cornerstones of the first-line therapy in HIV/AIDS patients and there are at least 15 FDA-approved antiretroviral
products that contain either TDF or TAF. However, due to their hydrophilic nature, low permeability, and
premature hydrolysis or activation, TDF and TAF both have a considerably low oral bioavailability of 25% and
40% respectively. Given that these drugs need to be administered for the lifetime of HIV patients, strategies to
improve oral bioavailability leading to optimal drug utilization and reduced therapeutic dose need to be
developed. Transformation of ionizable, highly hydrophilic or hydrophobic drugs into ionic liquids (ILs), low-
melting organic salts with a melting point < 100°C, has emerged as a novel and pharmaceutically viable approach
to improving pharmaceutical processability, solubility, permeability, and oral bioavailability of drugs. Our
preliminary data show that it is possible to transform ionizable hydrophobic drugs such as anthelmintic
benzimidazoles, and hydrophilic ionizable drugs such as metformin hydrochloride into low-melting ILs using
pharmaceutically acceptable fatty anion such as sodium docusate. Our preliminary further show that the
developed ILs can be efficiently packaged into polymeric nanomicelles further leading to improved oral delivery
and in vivo efficacy. Hence, we hypothesize that the transformation of TDF and TAF into amphiphilic ionic
liquids (ILs) using generally regarded as safe (GRAS) fatty permeation enhancers and their subsequent
incorporation into polymeric nanomicelles will improve oral bioavailability and in vivo antiviral efficacy. Our
preliminary data show that TDF and TAF can be rapidly and efficiently converted to amphiphilic ILs using GRAS
fatty permeation enhancers such as decanoic acid, undecylenic acid, oleic acid, and salcaprozic acid. Aim 1 will
focus on the development, characterization, and pharmacokinetic evaluation of polymeric nanomicelles
containing TDF-ILs or TAF ILs. Aim 2 will focus on the in vivo antiviral efficacy evaluation of oral polymeric
nanomicelles containing TDF IL in humanized BLT mouse model of HIV infection compared to pure TDF or TAF
to establish the proof of concept. The successful completion of this proposal is expected to lead to the
development of clinically viable pharmaceutical formulations containing ILs of tenofovir prodrugs to achieve
effective long-term management of HIV infection.

## Key facts

- **NIH application ID:** 10699620
- **Project number:** 1R21AI176907-01
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Abhijit A Date
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $230,250
- **Award type:** 1
- **Project period:** 2023-08-24 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10699620

## Citation

> US National Institutes of Health, RePORTER application 10699620, Ionic Liquids of tenofovir prodrugs for improved oral bioavailability and antiviral efficacy (1R21AI176907-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10699620. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*