用于将治疗性蛋白质递送至关节的明胶/6-硫酸软骨素微球。
Gelatin/chondroitin 6-sulfate microspheres for the delivery of therapeutic proteins to the joint.
作者信息
Brown K E, Leong K, Huang C H, Dalal R, Green G D, Haimes H B, Jimenez P A, Bathon J
机构信息
University of Maryland, College Park, USA.
出版信息
Arthritis Rheum. 1998 Dec;41(12):2185-95. doi: 10.1002/1529-0131(199812)41:12<2185::AID-ART13>3.0.CO;2-C.
OBJECTIVE
To develop a biodegradable, inflammation-responsive microsphere system for the intraarticular delivery of therapeutic proteins.
METHODS
Microspheres were synthesized by complex coacervation. Radiolabeled protein release and microsphere degradation were assessed by exposing the microspheres to human synovial fluids (SF) and recombinant gelatinase. Microsphere degradation was confirmed by scanning electron microscopy (SEM). Microsphere biocompatibility was evaluated in vitro by incubating the microspheres with human synoviocytes, and in vivo by injection into mouse joints.
RESULTS
Optimal microsphere formulation was developed. Significant (up to 100%) release of encapsulated protein occurred in SF samples with measurable metalloprotease activity, while release was minimal in SF with negligible activity. Dissolution of microspheres exposed to gelatinase was confirmed by SEM. Microspheres were found to be noncytotoxic in vitro, and noninflammatory in vivo.
CONCLUSION
Microsphere encapsulation is an inflammation-responsive and biocompatible system of protein delivery that holds promise for use in the delivery of therapeutic proteins to the joint.
目的
开发一种用于关节腔内递送治疗性蛋白质的可生物降解、炎症响应性微球系统。
方法
通过复凝聚法合成微球。通过将微球暴露于人类滑液（SF）和重组明胶酶来评估放射性标记蛋白质的释放和微球的降解。通过扫描电子显微镜（SEM）确认微球的降解。通过将微球与人滑膜细胞孵育在体外评估微球的生物相容性，并通过注射到小鼠关节在体内进行评估。
结果
开发出了最佳微球制剂。在具有可测量金属蛋白酶活性的SF样品中，包封的蛋白质出现显著（高达100%）释放，而在活性可忽略不计的SF中释放极少。通过SEM确认了暴露于明胶酶的微球的溶解。发现微球在体外无细胞毒性，在体内无炎症反应。
结论
微球包封是一种炎症响应性且生物相容的蛋白质递送系统，有望用于向关节递送治疗性蛋白质。
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