Document Detail


Protected 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.
MedLine Citation:
PMID:  23224976     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: 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 μg/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.
Authors:
Sandra Reichstetter; Gerardo M Castillo; Israel Rubinstein; Akiko Nishimoto-Ashfield; Manshun Lai; Cynthia C Jones; Aryamitra A Banerjee; Aryamitra Banjeree; Alex Lyubimov; Duane C Bloedow; Alexei Bogdanov; Elijah M Bolotin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-07
Journal Detail:
Title:  Pharmaceutical research     Volume:  30     ISSN:  1573-904X     ISO Abbreviation:  Pharm. Res.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-20     Completed Date:  2013-08-01     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  670-82     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Drug Carriers / chemistry*
Excipients / chemistry*
Female
Humans
Mice
Mice, Inbred BALB C
Micelles
Vasoactive Intestinal Peptide / administration & dosage*,  pharmacokinetics*,  pharmacology
Vasodilator Agents / administration & dosage*,  pharmacokinetics*,  pharmacology
Grant Support
ID/Acronym/Agency:
1R43AI082723/AI/NIAID NIH HHS; R43 AI082723/AI/NIAID NIH HHS; R43 AI098137/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Drug Carriers; 0/Excipients; 0/Micelles; 0/Vasodilator Agents; 37221-79-7/Vasoactive Intestinal Peptide
Comments/Corrections
Erratum In:
Pharm Res. 2013 Jul;30(7):1939
Note: Banjeree, Aryamitra [corrected to Banerjee, Aryamitra A]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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