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Journal article
Pharmacokinetic stability of macrocyclic peptide triazole HIV-1 inactivators alone and in liposomes
Journal of peptide science, v 25(4), e3155
01 Apr 2019
PMID: 30809901
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Previously, we reported the discovery of macrocyclic peptide triazoles (cPTs) that bind to HIV-1 Env gp120, inhibit virus cell infection with nanomolar potencies, and cause irreversible virion inactivation. Given the appealing virus-killing activity of cPTs and resistance to protease cleavage observed in vitro, we here investigated in vivo pharmacokinetics of the cPT AAR029b. AAR029b was investigated both alone and encapsulated in a PEGylated liposome formulation that was designed to slowly release inhibitor. Pharmacokinetic analysis in rats showed that the half-life of FITC-AAR029b was substantial both alone and liposome-encapsulated, 2.92 and 8.87hours, respectively. Importantly, liposome-encapsulated FITC-AAR029b exhibited a 15-fold reduced clearance rate from serum compared with the free FITC-cPT. This work thus demonstrated both the in vivo stability of cPT alone and the extent of pharmacokinetic enhancement via liposome encapsulation. The results obtained open the way to further develop cPTs as long-acting HIV-1 inactivators against HIV-1 infection.
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Details
- Title
- Pharmacokinetic stability of macrocyclic peptide triazole HIV-1 inactivators alone and in liposomes
- Creators
- Rachna Aneja - Drexel UniversityAntonella Grigoletto - University of PaduaAakansha Nangarlia - Drexel UniversityAdel A. Rashad - Drexel UniversitySteven Wrenn - Drexel UniversityJeffrey M. Jacobson - Temple UniversityGianfranco Pasut - University of PaduaIrwin Chaiken - Drexel University
- Publication Details
- Journal of peptide science, v 25(4), e3155
- Publisher
- Wiley
- Number of pages
- 12
- Grant note
- NIH P01 GM56550; NIH R01 GM111029 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Campbell Foundation 282795/5876 / Drexel University Clinical Translational Research Institute CTRI P01GM056550 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Chemical and Biological Engineering
- Web of Science ID
- WOS:000469860900003
- Scopus ID
- 2-s2.0-85062330429
- Other Identifier
- 991019168514904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Analytical