In-Vivo Evaluation of an In Situ Polymer Precipitation Delivery System for a Novel Natriuretic Peptide

Soo Ghim Lim, Subbu S. Venkatraman, John C Jr. Burnett, Horng Haur Chen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere52484
JournalPLoS One
Volume8
Issue number2
DOIs
StatePublished - Feb 18 2013

Fingerprint

natriuretic peptides
guanosine
Natriuretic Peptides
Cyclic GMP
polymers
Polymers
Bioactivity
Plasmas
drugs
Rats
excretion
Pharmaceutical Preparations
duration
rats
Radio
radio
Wistar Rats
Reading
Assays
Screening

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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 Jr.; Chen, Horng Haur.

In: PLoS One, Vol. 8, No. 2, e52484, 18.02.2013.

Research output: Contribution to journalArticle

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