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dc.contributor.authorReichstetter, Sandra
dc.contributor.authorCastillo, Gerardo M.
dc.contributor.authorRubinstein, Israel
dc.contributor.authorNishimoto-Ashfield, Akiko
dc.contributor.authorLai, Manshun
dc.contributor.authorJones, Cynthia C.
dc.contributor.authorBanerjee, Aryamitra A.
dc.contributor.authorLyubimov, Alex
dc.contributor.authorBloedow, Duane C.
dc.contributor.authorBogdanov, Alexei A. Jr.
dc.contributor.authorBolotin, Elijah M.
dc.date2022-08-11T08:10:50.000
dc.date.accessioned2022-08-23T17:21:48Z
dc.date.available2022-08-23T17:21:48Z
dc.date.issued2013-03-01
dc.date.submitted2015-01-05
dc.identifier.citationPharm Res. 2013 Mar;30(3):670-82. doi: 10.1007/s11095-012-0904-4. Epub 2012 Dec 7. <a href="http://dx.doi.org/10.1007/s11095-012-0904-4">Link to article on publisher's site</a>
dc.identifier.issn0724-8741 (Linking)
dc.identifier.doi10.1007/s11095-012-0904-4
dc.identifier.pmid23224976
dc.identifier.urihttp://hdl.handle.net/20.500.14038/48605
dc.description.abstractPURPOSE: To determine and compare pharmacokinetics and toxicity of two nanoformulations of Vasoactive Intestinal Peptide (VIP). METHODS: VIP was formulated using a micellar (Sterically Stabilized Micelles, SSM) and a polymer-based (Protected Graft Copolymer, PGC) nanocarrier at various loading percentages. VIP binding to the nanocarriers, pharmacokinetics, blood pressure, blood chemistry, and acute maximum tolerated dose (MTD) of the formulations after injection into BALB/c mice were determined. RESULTS: Both formulations significantly extend in vivo residence time compared to unformulated VIP. Formulation toxicity is dependent on loading percentage, showing major differences between the two carrier types. Both formulations increase in vivo potency of unformulated VIP and show acute MTDs at least 140 times lower than unformulated VIP, but still at least 100 times higher than the anticipated highest human dose, 1-5 mug/kg. These nanocarriers prevented a significant drop in arterial blood pressure compared to unformulated VIP. CONCLUSIONS: While both carriers enhance in vivo residence time compared to unformulated VIP and reduce the drop in blood pressure immediately after injection, PGC is the excipient of choice to extend residence time and improve the safety of potent therapeutic peptides such as VIP.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23224976&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1007/s11095-012-0904-4
dc.subjectAnimals
dc.subjectBlood Pressure
dc.subjectDrug Carriers
dc.subjectExcipients
dc.subjectFemale
dc.subjectHumans
dc.subjectMice
dc.subjectMice, Inbred BALB C
dc.subjectMicelles
dc.subjectVasoactive Intestinal Peptide
dc.subjectdosage
dc.subjectVasodilator Agents
dc.subjectMedicinal and Pharmaceutical Chemistry
dc.subjectOther Pharmacy and Pharmaceutical Sciences
dc.subjectRadiology
dc.titleProtected graft copolymer excipient leads to a higher acute maximum tolerated dose and extends residence time of vasoactive intestinal Peptide significantly better than sterically stabilized micelles
dc.typeJournal Article
dc.source.journaltitlePharmaceutical research
dc.source.volume30
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/radiology_pubs/91
dc.identifier.contextkey6497745
html.description.abstract<p>PURPOSE: To determine and compare pharmacokinetics and toxicity of two nanoformulations of Vasoactive Intestinal Peptide (VIP).</p> <p>METHODS: VIP was formulated using a micellar (Sterically Stabilized Micelles, SSM) and a polymer-based (Protected Graft Copolymer, PGC) nanocarrier at various loading percentages. VIP binding to the nanocarriers, pharmacokinetics, blood pressure, blood chemistry, and acute maximum tolerated dose (MTD) of the formulations after injection into BALB/c mice were determined.</p> <p>RESULTS: Both formulations significantly extend in vivo residence time compared to unformulated VIP. Formulation toxicity is dependent on loading percentage, showing major differences between the two carrier types. Both formulations increase in vivo potency of unformulated VIP and show acute MTDs at least 140 times lower than unformulated VIP, but still at least 100 times higher than the anticipated highest human dose, 1-5 mug/kg. These nanocarriers prevented a significant drop in arterial blood pressure compared to unformulated VIP.</p> <p>CONCLUSIONS: While both carriers enhance in vivo residence time compared to unformulated VIP and reduce the drop in blood pressure immediately after injection, PGC is the excipient of choice to extend residence time and improve the safety of potent therapeutic peptides such as VIP.</p>
dc.identifier.submissionpathradiology_pubs/91
dc.contributor.departmentDepartment of Radiology
dc.source.pages670-82


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