Recombinant spider silk particles for controlled delivery of protein drugs

被引:85
作者
Hofer, Markus [1 ]
Winter, Gerhard [1 ]
Myschik, Julia [1 ]
机构
[1] Univ Munich, Dept Pharm Pharmaceut Technol & Biopharmaceut, D-81377 Munich, Germany
关键词
Biomimetic material; Spider silk; Nanoparticle; Lysozyme; Drug delivery; BIODEGRADABLE MICROSPHERES; NANOPARTICLES; CHITOSAN; RELEASE; FIBROIN; PERMEABILITY; INSTABILITY; FORMULATION; POLYMERS; MODEL;
D O I
10.1016/j.biomaterials.2011.10.053
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The engineered and recombinant spider silk protein eADF4(C16) has been shown to be a promising biomaterial for the use as drug delivery system. In previous studies, eADF4(C16) particles were loaded with low molecular weight drugs exhibiting a positive net-charge and sufficient hydrophobicity. Here, we demonstrate that also macromolecular drugs like proteins can be loaded on eADF4(C16) particles. Using lysozyme as a model protein, remarkably high loading of up to 30% [w/w] was feasible and high loading efficiencies of almost 100% were obtained. Furthermore, using confocal laser scanning microscopy, it is demonstrated that fluorescently labeled lysozyme is not only adsorbed to the negatively charged particles' surface, but also diffusing into the matrix of eADF4(C16) particles. The release of lysozyme is shown to be dependent on the ionic strength and pH of the release medium. To improve the long-term stability of eADF4(C16) containing dispersions, lyophilization is shown as a suitable tool. Disaccharides (sucrose, trehalose) and mannitol served as stabilizers to prevent aggregation and/or particle degradation during freeze-drying. The slowly biodegradable eADF4(C16) particles are a promising new particulate drug carrier system for the delivery of susceptible drugs like therapeutic proteins. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1554 / 1562
页数:9
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