Doblhofer Elena, Scheibel Thomas
Thomas Scheibel, Lehrstuhl Biomaterialien, Fakultät für Ingenieurwissenschaften, Universität Bayreuth, Bayreuth, 95440, Germany.
J Pharm Sci. 2015 Mar;104(3):988-94. doi: 10.1002/jps.24300. Epub 2014 Dec 27.
Drug delivery carriers stabilize drugs and control their release, expanding the therapeutic window, and avoiding side effects of otherwise freely diffusing drugs in the human body. Materials used as carrier vehicles have to be biocompatible, biodegradable, nontoxic, and nonimmunogenic. Previously, particles made of the recombinant spider silk protein eADF4(C16) could be effectively loaded with positively and neutrally charged model substances. Here, a new positively charged variant thereof, named eADF4(κ16), has been engineered. Its particle formation is indistinguishable to that of polyanionic eADF4(C16), but in contrast polycationic eADF4(κ16) allows incorporation of negatively charged substances. Both high-molecular-weight substances, such as nucleic acids, and low-molecular-weight substances could be efficiently loaded onto eADF4(κ16) particles, and release of nucleic acids was shown to be well controlled.
药物递送载体可稳定药物并控制其释放，扩大治疗窗口，并避免原本在人体中自由扩散的药物产生副作用。用作载体的材料必须具有生物相容性、可生物降解性、无毒且无免疫原性。此前，由重组蜘蛛丝蛋白eADF4(C16)制成的颗粒可以有效地负载带正电荷和中性电荷的模型物质。在此，一种新的带正电荷的变体被设计出来，命名为eADF4(κ16)。其颗粒形成与聚阴离子eADF4(C16)的颗粒形成难以区分，但与聚阳离子eADF4(κ16)相反，它允许掺入带负电荷的物质。高分子量物质，如核酸，以及低分子量物质都可以有效地负载到eADF4(κ16)颗粒上，并且核酸的释放显示出得到了很好的控制。
