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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2013
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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) |
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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 |
_version_ |
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