title: In-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide.
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.
authors: School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.
authors: Soo Ghim
authors: SG
authors: Lim
authors: Subbu S
authors: SS
authors: Venkatraman
authors: John C
authors: JC
authors: Burnett
authors: Horng H
authors: HH
authors: Chen
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004546:Elapid Venoms / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005782:Gels; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry; D051381:Rats
chemical_list: C542600:CD-NP natriuretic peptide; D003692:Delayed-Action Preparations; D004546:Elapid Venoms; D005782:Gels; D011108:Polymers; D020098:Natriuretic Peptide, C-Type; D006152:Cyclic GMP