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Special Issue "HIV/AIDS Prevention Formulation Design and Optimization and Its Pharmacokinetic-Pharmacodynamic Evaluation"

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Special Issue Editors

Dr. José Gerardo Garcìa-Lerma

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Guest Editor

Laboratory Branch, Division of HIV Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA
Interests: HIV prevention; pre-exposure prophylaxis; multipurpose prevention technologies; preclinical research

Dr. S. Rahima Benhabbour

E-Mail Website
Guest Editor

Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599, USA
Interests: drug delivery devices; HIV; pre-exposure prophylaxis; long-acting delivery; multipurpose prevention technology (MPT)

Special Issue Information

Dear Colleagues,

Daily oral re-exposure prophylaxis (PrEP) has been highly effective in preventing HIV acquisition when taken as prescribed, although inadequate adherence reduces efficacy and public health benefits. The development of new long-acting PrEP modalities that do not require frequent dosing is being actively pursued in order to overcome suboptimal drug adherence to daily oral PrEP. A biomonthly injection of cabotegravir formulated as a nanoparticle suspension for intramuscular injection was the first long-acting regimen approved by the Food and Drug Administration (FDA) for PrEP in men and women.

This Special Isssue invites original research papers, communications or review articles that focus on the development of new long-acting drug formulations and controlled/extended release technologies for HIV PrEP, including (but not limited to) prodrug modifications, subdermal/subcutaneous implants, subcutaneous/intramuscular injectables, microarray patches, intravaginal rings, vaginal gels, inserts, and films. Articles studying pharmacokinetic/pharmacodynamic relationships in animal models are also considered as highly relevant for this Special Issue.

Dr. José Gerardo Garcìa-Lerma
Dr. S. Rahima Benhabbour
Guest Editors

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Keywords

HIV pre-exposure prophylaxis (PrEP)
long-acting PrEP
drug delivery systems
prodrug modification
pharmacokinetics
in vitro/in vivo correlation (IVIVC)
pharmacodynamics
animal models

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Research

Open AccessArticle

Preclinical Evaluation of Long-Acting Emtricitabine Semi-Solid Prodrug Nanoparticle Formulations

Christopher A. W. David

Caren L. Freel Meyers

Larisa Poluektova

Steve Rannard

and

Andrew Owen

Pharmaceutics 2023, 15(7), 1835; https://doi.org/10.3390/pharmaceutics15071835 - 27 Jun 2023

Viewed by 650

Abstract

Long-acting injectable (LAI) formulations promise to deliver patient benefits by overcoming issues associated with non-adherence. A preclinical assessment of semi-solid prodrug nanoparticle (SSPN) LAI formulations of emtricitabine (FTC) is reported here. Pharmacokinetics over 28 days were assessed in Wistar rats, New Zealand white rabbits, and Balb/C mice following intramuscular injection. Two lead formulations were assessed for the prevention of an HIV infection in NSG-cmah^−/− humanised mice to ensure antiviral activities were as anticipated according to the pharmacokinetics. Cmax was reached by 12, 48, and 24 h in rats, rabbits, and mice, respectively. Plasma concentrations were below the limit of detection (2 ng/mL) by 21 days in rats and rabbits, and 28 days in mice. Mice treated with SSPN formulations demonstrated undetectable viral loads (700 copies/mL detection limit), and HIV RNA remained undetectable 28 days post-infection in plasma, spleen, lung, and liver. The in vivo data presented here demonstrate that the combined prodrug/SSPN approach can provide a dramatically extended pharmacokinetic half-life across multiple preclinical species. Species differences in renal clearance of FTC mean that longer exposures are likely to be achievable in humans than in preclinical models. Full article

(This article belongs to the Special Issue HIV/AIDS Prevention Formulation Design and Optimization and Its Pharmacokinetic-Pharmacodynamic Evaluation)

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Open AccessArticle

Dose-Ranging Plasma and Genital Tissue Pharmacokinetics and Biodegradation of Ultra-Long-Acting Cabotegravir In Situ Forming Implant

Mackenzie L. Cottrell

Angela D. M. Kashuba

and

Soumya Rahima Benhabbour

Pharmaceutics 2023, 15(5), 1487; https://doi.org/10.3390/pharmaceutics15051487 - 13 May 2023

Viewed by 713

Abstract

HIV continues to affect millions of men and women worldwide. The development of long-acting injectables for HIV prevention can overcome adherence challenges with daily oral prevention regimens by reducing dosing frequency and stigma. We previously developed an ultra-long-acting injectable, biodegradable, and removeable in situ forming implant (ISFI) with cabotegravir (CAB) that demonstrated protection after multiple rectal SHIV challenges in female macaques. Here, we sought to further characterize CAB ISFI pharmacokinetics (PK) in mice by assessing the effect of dose and number of injections on CAB PK, time to completion of CAB release and polymer degradation, long-term genital tissue PK, and CAB PK tail after implant removal. CAB concentrations in plasma were above the benchmark for protection for 11–12 months with proportionality between dose and drug exposure. CAB ISFI exhibited high concentrations in vaginal, cervical, and rectal tissues for up to 180 days. Furthermore, depots were easily retrievable up to 180 days post-administration with up to 34% residual CAB and near complete (85%) polymer degradation quantified in depots ex vivo. After depot removal, results demonstrated a median 11-fold decline in CAB plasma concentrations across all doses. Ultimately, this study provided critical PK information for the CAB ISFI formulation that could aid in its future translation to clinical studies. Full article

(This article belongs to the Special Issue HIV/AIDS Prevention Formulation Design and Optimization and Its Pharmacokinetic-Pharmacodynamic Evaluation)

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Special Issue "HIV/AIDS Prevention Formulation Design and Optimization and Its Pharmacokinetic-Pharmacodynamic Evaluation"

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