Mechanisms of monoclonal antibody stabilization and release from silk biomaterials.
Mechanisms of monoclonal antibody stabilization and release from silk biomaterials.
复制标题
DOI：
10.1016/j.biomaterials.2013.06.039
复制
发表时间：
2013-10
期刊：
影响因子：
14
通讯作者：
Kaplan, David L.
中科院分区：
文献类型：
--
作者：
Guziewicz, Nicholas A.;Massetti, Andrew J.;Perez-Ramirez, Bernardo J.;Kaplan, David L.
尽管抗体因其特异性和有效性而在广泛的治疗应用中不断发展，但稳定和持续的抗体治疗系统的可用性仍然是一个重大的临床挑战。对蛋白质-基质相互作用的机械理解对于这类系统的发展至关重要，目前还缺乏一种模式来指导这一领域。我们报告了通过使用基于丝胶的定义明确的基质与单抗相结合的机制洞察力来解决这一需求。评估了抗体载量、基质密度、电荷相互作用、疏水性和水的可获取性等变量，以阐明抗体从生物材料基质中释放的机制。结果表明，抗体的释放主要受疏水相互作用和水合阻力的控制，并受丝素基质化学成分、多肽结构域分布和蛋白质密度的控制。二次离子排斥也是抗体稳定和释放的关键。通过游离蛋氨酸掺入的基质修饰被发现是一种有效的策略，以减轻包埋引起的抗体氧化。此外，这些研究突出了一种表征方法，以提高对其他蛋白质持续递送系统的理解和开发，并具有广泛的适用性，适用于快速发展的单抗领域。
The availability of stabilization and sustained delivery systems for antibody therapeutics remains a major clinical challenge, despite the growing development of antibodies for a wide range of therapeutic applications due to their specificity and efficacy. A mechanistic understanding of protein-matrix interactions is critical for the development of such systems and is currently lacking as a mode to guide the field. We report mechanistic insight to address this need by using well-defined matrices based on silk gels, in combination with a monoclonal antibody. Variables including antibody loading, matrix density, charge interactions, hydrophobicity and water access were assessed to clarify mechanisms involved in the release of antibody from the biomaterial matrix. The results indicate that antibody release is primarily governed by hydrophobic interactions and hydration resistance, which are controlled by silk matrix chemistry, peptide domain distribution and protein density. Secondary ionic repulsions are also critical in antibody stabilization and release. Matrix modification by free methionine incorporation was found to be an effective strategy for mitigating encapsulation induced antibody oxidation. Additionally, these studies highlight a characterization approach to improve the understanding and development of other protein sustained delivery systems, with broad applicability to the rapidly developing monoclonal antibody field.
登录
查看更多内容
影响因子：
14
作者：
Panilaitis, B;Altman, GH;Kaplan, DL
通讯作者：
Kaplan, DL
影响因子：
3.8
作者：
DONG, AC;PRESTRELSKI, SJ;CARPENTER, JF
通讯作者：
CARPENTER, JF
DOI：
10.1016/j.bioeng.2007.02.001
发表时间：
2007-06-01
期刊：
BIOMOLECULAR ENGINEERING
影响因子：
--
作者：
Milowska, Katarzyna;Gabryelak, Teresa
通讯作者：
Gabryelak, Teresa
影响因子：
6.2
作者：
Hines, Daniel J.;Kaplan, David L.
通讯作者：
Kaplan, David L.
影响因子：
120.1
作者：
Nelson, Aaron L.;Dhimolea, Eugen;Reichert, Janice M.
通讯作者：
Reichert, Janice M.