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Cationic and thermosensitive protamine conjugated gels for enhancing sustained human growth hormone delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
9841 648 2010 11 PDF Available
Title
Cationic and thermosensitive protamine conjugated gels for enhancing sustained human growth hormone delivery
Abstract

Thermosensitive and cationic poly(organophosphazenes) were designed and synthesized for the sustained delivery of human growth hormone (hGH) charged negatively at the physiological conditions to enhance greatly patient convenience and to improve efficacy and stability. Protamine for a complex formation with hGH was chosen and conjugated to carboxylic acid-terminated poly(organophosphazenes) by a covalent amide linkage. The aqueous solution of the cationic polymer conjugates formed a gel at 37 °C regardless of hGH presence. When the conjugate solution was mixed with hGH solution, a complex was formed and free hGH could be released from the complex. In the in vitro and in vivo release studies of hGH/polymer-protamine conjugate, the initial burst release was suppressed and the release period was prolonged as the protamine amount was increased. In the PK and PD studies with cynomolgus monkeys, a single administration of hGH/cationic polymer conjugate induced the elevated plasma level of hGH until 5 days and also elevated plasma level of IGF-1 as a function of free hGH until 13 days. These results suggest that the injectable, thermosensitive, and cationic poly(organophosphazene)-protamine conjugate may hold a great potential as an effective carrier for sustained release of hGH with improved patient convenience, stability and efficacy.

Keywords
Human growth hormone (hGH); Protamine; Thermosensitive hydrogel; Ionic interaction; Sustained protein delivery; Complexation
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Cationic and thermosensitive protamine conjugated gels for enhancing sustained human growth hormone delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 6, February 2010, Pages 1349–1359
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us