PEGylated substance P augments therapeutic angiogenesis in diabetic critical limb ischemia

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dc.contributor.authorPark, Hyun-Jiko
dc.contributor.authorKim, Sunako
dc.contributor.authorJeon, Eun Jeko
dc.contributor.authorSong, In Taekko
dc.contributor.authorLee, Haeshinko
dc.contributor.authorSon, Youngsookko
dc.contributor.authorHong, Hyun Sookko
dc.contributor.authorCho, Seung-Wooko
dc.date.accessioned2019-08-21T08:20:06Z-
dc.date.available2019-08-21T08:20:06Z-
dc.date.created2019-08-19-
dc.date.issued2019-10-
dc.identifier.citationJOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY, v.78, pp.396 - 409-
dc.identifier.issn1226-086X-
dc.identifier.urihttp://hdl.handle.net/10203/264360-
dc.description.abstractSubstance P (SP) is a therapeutic peptide that has been widely used to induce angiogenesis and tissue regeneration. However, its therapeutic efficacy is often limited due to rapid degradation in vivo and a short half-life (1 min) after systemic administration. In the present study, we chemically modified SP with polyethylene glycol (PEG) to generate long-lasting formulations with increased stability and extended retention time in vivo and evaluated their ability to enhance therapeutic angiogenesis. Compared to the unmodified SP, PEGylated SP (PEG-SP) exhibited significantly increased half-life in vivo ('360-fold increase in normal mouse and (similar to)120-fold increase in diabetic mouse). Systemic injection of PEG SP led to a marked increase in therapeutic efficacy and angiogenesis in diabetic hindlimb ischemia, as evident from the remarkable improvement in salvage of ischemic limb and recovery of blood perfusion in diabetic mice with limb ischemia. These formulations increased endogenous stem cell mobilization to the injured site and modulated the immune system to increase microvessel formation and reduce systemic inflammation. Importantly, PEGylation efficiently reduced the injection doses of SP while still maintaining its therapeutic efficacy. To conclude, our study demonstrated that PEG-SP formulations exhibited an improved in vivo pharmacokinetic profile with enhanced efficacy and clinically acceptable treatment regimens, thus acting as a potent therapeutic for diabetic ischemia and inflammation. (C) 2019 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.-
dc.languageEnglish-
dc.publisherELSEVIER SCIENCE INC-
dc.titlePEGylated substance P augments therapeutic angiogenesis in diabetic critical limb ischemia-
dc.typeArticle-
dc.identifier.wosid000477689400042-
dc.identifier.scopusid2-s2.0-85066612730-
dc.type.rimsART-
dc.citation.volume78-
dc.citation.beginningpage396-
dc.citation.endingpage409-
dc.citation.publicationnameJOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY-
dc.identifier.doi10.1016/j.jiec.2019.05.030-
dc.contributor.localauthorLee, Haeshin-
dc.contributor.nonIdAuthorPark, Hyun-Ji-
dc.contributor.nonIdAuthorKim, Suna-
dc.contributor.nonIdAuthorJeon, Eun Je-
dc.contributor.nonIdAuthorSon, Youngsook-
dc.contributor.nonIdAuthorHong, Hyun Sook-
dc.contributor.nonIdAuthorCho, Seung-Woo-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorSubstance P-
dc.subject.keywordAuthorPEGylation-
dc.subject.keywordAuthorTherapeutic angiogenesis-
dc.subject.keywordAuthorDiabetic limb ischemia-
dc.subject.keywordPlusNEUTRAL ENDOPEPTIDASE ACTIVITY-
dc.subject.keywordPlusPEPTIDE-
dc.subject.keywordPlusCELLS-
dc.subject.keywordPlusINTERNALIZATION-
dc.subject.keywordPlusPROLIFERATION-
dc.subject.keywordPlusINFLAMMATION-
dc.subject.keywordPlusDYSFUNCTION-
dc.subject.keywordPlusIMPAIRMENT-
dc.subject.keywordPlusRECEPTORS-
dc.subject.keywordPlusMIGRATION-
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