A Holistic Review of the Preclinical Landscape for Long-Acting Anti-infective Drugs Using HIV as a Paradigm

Neary, Megan ORCID: 0000-0002-4960-2139, Owen, Andrew ORCID: 0000-0002-9819-7651 and Olagunju, Adeniyi ORCID: 0000-0002-6588-5749 (2022) A Holistic Review of the Preclinical Landscape for Long-Acting Anti-infective Drugs Using HIV as a Paradigm. Clinical Infectious Diseases, 75 (Supple). S490-S497.

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Abstract

<jats:title>Abstract</jats:title> <jats:p>Lack of predictive preclinical models is a key contributor to the steep attrition rate in drug development. Successful clinical translation may be higher for new chemical entities or existing approved drugs reformulated for long-acting (LA) administration if preclinical studies designed to identify any new uncertainties are predictive of human exposure and response. In this review, we present an overview of standard preclinical assessments deployed for LA formulations and delivery systems, using human immunodeficiency virus LA therapeutics preclinical development as a paradigm. Key progress in the preclinical development of novel LA antiretrovirals formulations and delivery systems are summarized, including bispecific broadly neutralizing monoclonal antibody and small molecule technologies for codelivery of multiple drugs with disparate solubility properties. There are new opportunities to take advantage of recent developments in tissue engineering and 3-dimensional in vitro modeling to advance preclinical modeling of anti-infective activity, developmental and reproductive toxicity assessment, and to apply quantitative modeling and simulation strategies. These developments are likely to drive the progression of more LA anti-infective drugs and multipurpose technologies into clinical development in the coming years.</jats:p>

Item Type:	Article
Uncontrolled Keywords:	long-acting, antiretroviral, preclinical, in vitro models
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	22 Nov 2022 11:07
Last Modified:	18 Apr 2023 17:13
DOI:	10.1093/cid/ciac685
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3166314