發(fā)展可控的藥物緩釋裝置是材料科學(xué)家所面臨的挑戰(zhàn)之一,。Macromolecular Bioscience雜志發(fā)表一篇論文稱,,研究人員William L. Murphy等將一種動態(tài)的蛋白質(zhì)-鈣調(diào)蛋白(calmodulin)置入了水凝膠的高分子結(jié)構(gòu)當(dāng)中,合成了一種新型的材料,,它可以在受到某種分子刺激的條件下釋放出所包裹的藥物,。
鈣調(diào)蛋白在觸發(fā)分子的作用下會發(fā)生構(gòu)型的改變,從而引起水凝膠體積的減小,,釋放出所包裹的藥物成分,。科學(xué)家們將這種水凝膠放入臨床使用的微球當(dāng)中,,這些微球可以在注射的過程中保護水凝膠的幾何結(jié)構(gòu),,避免模型藥物(model drug)及血管內(nèi)皮生長因子(vascular endothelial growth factor)受到影響。,。
科學(xué)家們已經(jīng)發(fā)現(xiàn)有數(shù)百種會發(fā)生構(gòu)型變化的蛋白質(zhì),。所以上面的這種控制藥物緩釋的方法也可以進一步擴展到更多不同種類的觸發(fā)分子。(生物谷 Bioon.com)
doi:10.1002/mabi.200900382
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Triggered Drug Release from Dynamic Microspheres via a Protein Conformational Change
William J. King, Nicholas J. Pytel, Kelvin Ng, William L. Murphy
In this study we formed and characterized dynamic hydrogel microspheres in which a protein conformational change was used to control microsphere volume changes and the release of an encapsulated drug. In particular, a specific biochemical ligand, trifluoperazine, induced calmodulin's nanometer scale conformation change, which translated to a 48.7% microsphere volume decrease. This specific, ligand-induced volume change triggered the release of a model drug, vascular endothelial growth factor (VEGF), at pre-determined times. After release from the microspheres, 85.6 ± 10.5% of VEGF was in its native conformation. Taken together, these results suggest that protein conformational change could serve as a useful mechanism to control drug release from dynamic hydrogels.