In-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide.

This study reports on the release of a novel natriuretic peptide, CD-NP, from an in situ polymer precipitation delivery system. Following extensive screening of in-vitro release profiles, an in-vivo evaluation of the efficacy of the delivery system was carried out in Wistar rats. Gel injection was p...

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Main Authors: Soo Ghim Lim, Subbu S Venkatraman, John C Burnett, Horng H Chen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23441143/?tool=EBI
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author Soo Ghim Lim
Subbu S Venkatraman
John C Burnett
Horng H Chen
author_facet Soo Ghim Lim
Subbu S Venkatraman
John C Burnett
Horng H Chen
author_sort Soo Ghim Lim
collection DOAJ
description This study reports on the release of a novel natriuretic peptide, CD-NP, from an in situ polymer precipitation delivery system. Following extensive screening of in-vitro release profiles, an in-vivo evaluation of the efficacy of the delivery system was carried out in Wistar rats. Gel injection was performed subcutaneously on the back of the rats. A secondary messenger, cyclic Guanosine 3'5' Monophosphate (cGMP), was tested for verification of CD-NP bioactivity, in addition to direct measurements of CD-NP levels in plasma and urine using a radio-immuno assay. Plasma evaluation showed an elevated level of CD-NP over 3 weeks' duration. Unexpectedly, plasma cGMP level followed a decreasing trend over the same duration despite high CD-NP level. Loss of drug bioactivity was ruled out as a high level of CD-NP and cGMP excretion was observed in the treatment group as compared to baseline readings. This unexpected low-plasma cGMP levels and high-urinary cGMP excretion suggest that there might be other compensatory responses to regulation of the CDNP bioactivity as a result of the high drug dosing. The results stress the importance of assessing the overall bioactivity of released drug (in-vivo) concurrently in addition to measuring its concentrations, to determine the correct release profile.
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spelling doaj.art-98b25912d8324f0482bf5cc48f22e2562022-12-21T23:09:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5248410.1371/journal.pone.0052484In-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide.Soo Ghim LimSubbu S VenkatramanJohn C BurnettHorng H ChenThis study reports on the release of a novel natriuretic peptide, CD-NP, from an in situ polymer precipitation delivery system. Following extensive screening of in-vitro release profiles, an in-vivo evaluation of the efficacy of the delivery system was carried out in Wistar rats. Gel injection was performed subcutaneously on the back of the rats. A secondary messenger, cyclic Guanosine 3'5' Monophosphate (cGMP), was tested for verification of CD-NP bioactivity, in addition to direct measurements of CD-NP levels in plasma and urine using a radio-immuno assay. Plasma evaluation showed an elevated level of CD-NP over 3 weeks' duration. Unexpectedly, plasma cGMP level followed a decreasing trend over the same duration despite high CD-NP level. Loss of drug bioactivity was ruled out as a high level of CD-NP and cGMP excretion was observed in the treatment group as compared to baseline readings. This unexpected low-plasma cGMP levels and high-urinary cGMP excretion suggest that there might be other compensatory responses to regulation of the CDNP bioactivity as a result of the high drug dosing. The results stress the importance of assessing the overall bioactivity of released drug (in-vivo) concurrently in addition to measuring its concentrations, to determine the correct release profile.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23441143/?tool=EBI
spellingShingle Soo Ghim Lim
Subbu S Venkatraman
John C Burnett
Horng H Chen
In-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide.
PLoS ONE
title In-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide.
title_full In-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide.
title_fullStr In-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide.
title_full_unstemmed In-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide.
title_short In-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide.
title_sort in vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23441143/?tool=EBI
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AT johncburnett invivoevaluationofaninsitupolymerprecipitationdeliverysystemforanovelnatriureticpeptide
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