The biological efficiency and bioavailability of human growth hormone delivered using injectable, ionic, thermosensitive poly(organophosphazene)-polyethylenimine conjugate hydrogels

Title
The biological efficiency and bioavailability of human growth hormone delivered using injectable, ionic, thermosensitive poly(organophosphazene)-polyethylenimine conjugate hydrogels
Authors
서보배박미란전창주이재열송수창
Keywords
Human growth hormone (hGH); Polyethylenimine (PEI); Thermosensitive hydrogel; Ionic interaction; Sustained delivery
Issue Date
2011-11
Publisher
Biomaterials
Citation
VOL 32, NO 32, 8271-8280
Abstract
We have endeavored to develop injectable, thermosensitive, biodegradable hydrogels that prolong human growth hormone (hGH) release, improving bioavailability through introducing balanced ionic interactions. Cationic poly(organophosphazene)-polyethylenimine (PEI, 1.8 kDa) conjugate hydrogels were synthesized as those hydrogels for sustained delivery of anionic hGH with proper ionic strength of association/dissociation. We have additionally prepared different chain lengths of a-amino-u-methoxypoly( ethylene glycol) (AMPEG550 and AMPEG750) for the synthesis of conjugates as a means to control hydrogel degradation rates. All Aqueous solutions of PEI-conjugates became hydrogels hydrolyzable in proportion to AMPEG molecular weight at body temperature; these PEI-conjugates complexed with hGH and extended hGH release in vitro. In pharmacokinetic studies of hGH behavior in SD rats, hydrogels of PEI-conjugate/hGH complexes could suppress the initial burst-phase, and extend the duration, of release, as well as increasing of area under the curve (AUC) compared to controls including hGH solution or nonionic hydrogel. In a hypophysectomized rat model, the biological efficacy of hGH delivered from PEIconjugate/ hGH complex hydrogels was equivalent to that from daily administration over four days based on body weight gain and width of the tibial growth plate. These results suggest that ionic, thermosensitive, poly(organophosphazene)-PEI-conjugate hydrogel demonstrates potential as an injectable depot for sustained delivery of bioavailable hGH.
URI
http://pubs.kist.re.kr/handle/201004/41210
ISSN
0142-9612
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KIST Publication > Article
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