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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| Format: | Online |
| Language: | English |
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Public Library of Science
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575325/ |
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pubmed-3575325 |
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pubmed-35753252013-02-25 In-Vivo Evaluation of an In Situ Polymer Precipitation Delivery System for a Novel Natriuretic Peptide Lim, Soo Ghim Venkatraman, Subbu S. Burnett, John C. Chen, Horng H. Research Article 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. Public Library of Science 2013-02-18 /pmc/articles/PMC3575325/ /pubmed/23441143 http://dx.doi.org/10.1371/journal.pone.0052484 Text en © 2013 Lim et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Lim, Soo Ghim Venkatraman, Subbu S. Burnett, John C. Chen, Horng H. |
| spellingShingle |
Lim, Soo Ghim Venkatraman, Subbu S. Burnett, John C. Chen, Horng H. In-Vivo Evaluation of an In Situ Polymer Precipitation Delivery System for a Novel Natriuretic Peptide |
| author_facet |
Lim, Soo Ghim Venkatraman, Subbu S. Burnett, John C. Chen, Horng H. |
| author_sort |
Lim, Soo Ghim |
| 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 |
| 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. |
| publisher |
Public Library of Science |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575325/ |
| _version_ |
1611955772471640064 |