Molecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide

Abstract Elastin-like polypeptides (ELP) are engineered proteins that consist of repetitions of a five amino acid motif, and their composition is easily modified to adjust their physical properties and attach therapeutics. Because of the repetitive nature of the ELP sequence, polymer size is particu...

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Autores principales:	Marija Kuna, Fakhri Mahdi, Alejandro R. Chade, Gene L. Bidwell
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8dd0e54fcfa440c3ba3d326e23c06e82
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spelling	oai:doaj.org-article:8dd0e54fcfa440c3ba3d326e23c06e822021-12-02T15:07:49ZMolecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide10.1038/s41598-018-24897-92045-2322https://doaj.org/article/8dd0e54fcfa440c3ba3d326e23c06e822018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24897-9https://doaj.org/toc/2045-2322Abstract Elastin-like polypeptides (ELP) are engineered proteins that consist of repetitions of a five amino acid motif, and their composition is easily modified to adjust their physical properties and attach therapeutics. Because of the repetitive nature of the ELP sequence, polymer size is particularly amenable to manipulation. ELP fusion proteins are being actively developed as therapeutics for many disease applications, and how the ELP size and shape affects its pharmacokinetics and biodistribution is a critical question for the general field of ELP drug delivery. To address this, we generated a library of ELPs ranging in size from 25 kDa to 110 kDa. Terminal plasma half-life was directly proportional to polymer size, and organ biodistribution was also size dependent. The kidneys accumulated the highest levels of ELP of all sizes, followed by the liver. Within the kidney, most ELP was found in the proximal tubule, but intra-renal localization shifted from exclusively cortical to a mixture of cortical and medullary as ELP size increased.Marija KunaFakhri MahdiAlejandro R. ChadeGene L. BidwellNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marija Kuna Fakhri Mahdi Alejandro R. Chade Gene L. Bidwell Molecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide
description	Abstract Elastin-like polypeptides (ELP) are engineered proteins that consist of repetitions of a five amino acid motif, and their composition is easily modified to adjust their physical properties and attach therapeutics. Because of the repetitive nature of the ELP sequence, polymer size is particularly amenable to manipulation. ELP fusion proteins are being actively developed as therapeutics for many disease applications, and how the ELP size and shape affects its pharmacokinetics and biodistribution is a critical question for the general field of ELP drug delivery. To address this, we generated a library of ELPs ranging in size from 25 kDa to 110 kDa. Terminal plasma half-life was directly proportional to polymer size, and organ biodistribution was also size dependent. The kidneys accumulated the highest levels of ELP of all sizes, followed by the liver. Within the kidney, most ELP was found in the proximal tubule, but intra-renal localization shifted from exclusively cortical to a mixture of cortical and medullary as ELP size increased.
format	article
author	Marija Kuna Fakhri Mahdi Alejandro R. Chade Gene L. Bidwell
author_facet	Marija Kuna Fakhri Mahdi Alejandro R. Chade Gene L. Bidwell
author_sort	Marija Kuna
title	Molecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide
title_short	Molecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide
title_full	Molecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide
title_fullStr	Molecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide
title_full_unstemmed	Molecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide
title_sort	molecular size modulates pharmacokinetics, biodistribution, and renal deposition of the drug delivery biopolymer elastin-like polypeptide
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/8dd0e54fcfa440c3ba3d326e23c06e82
work_keys_str_mv	AT marijakuna molecularsizemodulatespharmacokineticsbiodistributionandrenaldepositionofthedrugdeliverybiopolymerelastinlikepolypeptide AT fakhrimahdi molecularsizemodulatespharmacokineticsbiodistributionandrenaldepositionofthedrugdeliverybiopolymerelastinlikepolypeptide AT alejandrorchade molecularsizemodulatespharmacokineticsbiodistributionandrenaldepositionofthedrugdeliverybiopolymerelastinlikepolypeptide AT genelbidwell molecularsizemodulatespharmacokineticsbiodistributionandrenaldepositionofthedrugdeliverybiopolymerelastinlikepolypeptide
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Molecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide

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