Unknown

Dataset Information

0

Pharmacokinetic stability of macrocyclic peptide triazole HIV-1 inactivators alone and in liposomes.


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 8.87 hours, 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.

SUBMITTER: Aneja R 

PROVIDER: S-EPMC6467816 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Pharmacokinetic stability of macrocyclic peptide triazole HIV-1 inactivators alone and in liposomes.

Aneja Rachna R   Grigoletto Antonella A   Nangarlia Aakansha A   Rashad Adel A AA   Wrenn Steven S   Jacobson Jeffrey M JM   Pasut Gianfranco G   Chaiken Irwin I  

Journal of peptide science : an official publication of the European Peptide Society 20190227 4


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 rele  ...[more]

Similar Datasets

| S-EPMC5614861 | biostudies-literature
| S-EPMC4497506 | biostudies-literature
| S-EPMC3810028 | biostudies-literature
| S-EPMC5572807 | biostudies-literature
| S-EPMC3731144 | biostudies-literature
| S-EPMC2636857 | biostudies-literature
| S-EPMC3035117 | biostudies-other
| S-EPMC3881423 | biostudies-literature
| S-EPMC8079196 | biostudies-literature
| S-EPMC3263404 | biostudies-literature