Photopolymerized thermosensitive hydrogels for tailorable diffusion-controlled protein delivery

JOURNAL OF CONTROLLED RELEASE

卷:140

Article; Proceedings Paper

Censi, R.^1,2  Vermonden, T.¹  van Steenbergen, M. J.¹  Deschout, H.³  Braeckmans, K.³  De Smedt, S. C.³  van Nostrum, C. F.¹  di Martino, P.²  Hennink, W. E.¹ 

[1] Univ Utrecht, Dept Pharmaceut, UIPS, NL-3508 TB Utrecht, Netherlands

[2] Univ Camerino, Dept Chem Sci, I-62032 Camerino, MC, Italy

[3] Univ Ghent, Dept Pharmaceut, Lab Gen Biochem & Phys Chem, B-9000 Ghent, Belgium

关键词: Injectable thermosensitive hydrogels;    Photopolymerization;    Swelling;    Degradation;    Fickian diffusion;   

DOI  :  10.1016/j.jconrel.2009.06.003

来源: Elsevier

【 摘 要 】

In this paper the possibility to tailor degradation and protein release behavior of photo polymerized thermosensitive hydrogels is studied. The hydrogels consist of ABA triblock copolymer, in which the thermosensitive A-blocks are methacrylated poly(N-(2-hydroxypropyl)methacrylamide lactate)s and the B-block is poly(ethylene glycol) with molecular weight of 10 kDa. These hydrogels are prepared by using a combination of physical and chemical cross-linking methods. When a solution of a thermosensitive methacrylated p(HPMAm-lac)-PEG-p(HPMAm-lac) is heated above its cloud point a viscoelastic material is obtained, which can be stabilized by introducing covalent cross-links by photopolymerization. By varying the polymer concentration, hydrogels with different mechanical properties are formed, of which the cross-linking density, mesh size, swelling and degradation behavior can be tuned. It was demonstrated that the release rate of three model proteins (lysozyme, BSA and IgG, with hydrodynamic diameters ranging from 4.1 to 10.7 nm) depended on the protein size and hydrogel molecular weight between cross-links and was governed by the Fickian diffusion. Importantly, the encapsulated proteins were quantitatively released and the secondary structure and the enzymatic activity of lysozyme were fully preserved demonstrating the protein friendly nature of the studied delivery system. (C) 2009 Elsevier B.V. All rights reserved.

【 授权许可】

Free