Functionalized injectable hydrogels for controlled insulin delivery

Abstract The concept of this research is using poly(β-amino ester) (PAE) as a duo-functional group for synthesis of the novel sensitive injectable hydrogel for controlled drug/protein delivery. Firstly, PAE made of 1,4-butanediol diacrylate and 4,4′-trimethylene dipiperidine is used as a pH-sensitiv...

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Bibliographic Details
Published in:	Biomaterials Vol. 29; no. 16; pp. 2527 - 2534
Main Authors:	Huynh, Dai P, Nguyen, Minh K, Pi, Bong S, Kim, Min S, Chae, Su Y, Lee, Kang C, Kim, Bong S, Kim, Sung W, Lee, Doo S
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Ltd 01-06-2008
Subjects:	Advanced Basic Science Animals Controlled release Dentistry Drug Delivery Systems Esters - chemical synthesis Hydrogel Hydrogel, Polyethylene Glycol Dimethacrylate - chemical synthesis Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacokinetics Injections, Subcutaneous Insulin - administration & dosage Insulin - pharmacokinetics Insulin delivery Male pH/temperature-sensitive Phase Transition Polyesters - chemical synthesis Polyethylene Glycols - chemical synthesis Polymers - chemical synthesis Rats Rats, Sprague-Dawley Hydrogel pH/temperature-sensitive Insulin delivery Controlled release
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Summary:	Abstract The concept of this research is using poly(β-amino ester) (PAE) as a duo-functional group for synthesis of the novel sensitive injectable hydrogel for controlled drug/protein delivery. Firstly, PAE made of 1,4-butanediol diacrylate and 4,4′-trimethylene dipiperidine is used as a pH-sensitive moiety to conjugat to the temperature-sensitive biodegradable triblock copolymer of poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) to manufacture pH/temperature-sensitive injectable hydrogel of pentablock copolymer PAE–PCL–PEG–PCL–PAE. Furthermore, the cationic nature of PAE is used as the second function to make the ionic complexes with anionic biomolecule loaded into the hydrogel such as insulin. As a result, the release of drug/protein from this hydrogel device can be controlled by the degradation of copolymer. Sol–gel phase transition behavior of PAE–PCL–PEG–PCL–PAE block copolymer was investigated; the results showed that the aqueous media of the pentablock copolymer changed from a sol to a gel phase with increasing temperature and pH. The effect of anionic biomolecule such as insulin on sol–gel phase transition, degradation of the complex gel of the material with insulin was studied in vitro. Then the schematic of the ionic complexes between positive charges in PAE and the negatively charges in protein was simulated. In addition, the mechanism of controlled release behavior of insulin from the complex gel was supposed, which includes the chemically-controlled and diffusion-controlled stages. To prove the simulations, the cumulative release of the protein from the complex gel was investigated in vitro with different methods. Furthermore, the pharmacokinetic release of insulin from the complex gel in vivo on male Sprague-Dawley (SD) rats was compared with that from triblock copolymer hydrogel of PCL–PEG–PCL.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0142-9612 1878-5905
DOI:	10.1016/j.biomaterials.2008.02.016