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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Autores principales: Soo Ghim Lim, Subbu S Venkatraman, John C Burnett, Horng H Chen
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/98b25912d8324f0482bf5cc48f22e256
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spelling oai:doaj.org-article:98b25912d8324f0482bf5cc48f22e2562021-11-18T07:57:14ZIn-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide.1932-620310.1371/journal.pone.0052484https://doaj.org/article/98b25912d8324f0482bf5cc48f22e2562013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23441143/?tool=EBIhttps://doaj.org/toc/1932-6203This 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.Soo Ghim LimSubbu S VenkatramanJohn C BurnettHorng H ChenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e52484 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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.
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.
format article
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
title 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_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_sort in-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/98b25912d8324f0482bf5cc48f22e256
work_keys_str_mv AT sooghimlim invivoevaluationofaninsitupolymerprecipitationdeliverysystemforanovelnatriureticpeptide
AT subbusvenkatraman invivoevaluationofaninsitupolymerprecipitationdeliverysystemforanovelnatriureticpeptide
AT johncburnett invivoevaluationofaninsitupolymerprecipitationdeliverysystemforanovelnatriureticpeptide
AT hornghchen invivoevaluationofaninsitupolymerprecipitationdeliverysystemforanovelnatriureticpeptide
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