Competitive Affinity Release for Long-Term Delivery of Antibodies from Hydrogels

被引：38
作者：
Huynh, Vincent [1 ]
Wylie, Ryan G. [1 ]
机构：
[1] McMaster Univ, Dept Chem & Chem Biol, 1280 Main St W ABB 261A, Hamilton, ON L8S 4M1, Canada
来源：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2018年 / 57卷 / 13期
基金：
加拿大自然科学与工程研究理事会; 加拿大创新基金会;
关键词：
antibodies; competitive interactions; drug delivery; materials science; protein modifications; GROWTH-FACTOR DELIVERY; FUNCTIONALIZED HYDROGELS; INJECTABLE HYDROGELS; SUSTAINED-RELEASE; IN-VITRO; HEPARIN; BINDING; SYSTEMS; BIOTIN; VEGF;
D O I：
10.1002/anie.201713428
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
With increased clinical use of antibodies, long-term delivery strategies are needed to decrease injection frequency and improve health outcomes. A three-component drug-delivery system was developed for competitive affinity release of a streptavidin-antibody conjugate from agarose-desthiobiotin hydrogels via controlled dissolution of sparingly soluble biotin derivatives. The antibody conjugate was localized in the hydrogel through streptavidin-desthiobiotin complexation. Dissolution of sparingly soluble biotin derivatives disrupts streptavidin-desthiobiotin complexation for controlled release of the antibody conjugate. Release was tuned by altering the total biotin derivative concentration without further hydrogel or antibody modification. First-order tunable release of bioactive Avastin, a therapeutic anti-VEGF antibody, was demonstrated from a non-cytotoxic system for over 100days.
引用
收藏
页码：3406 / 3410
页数：5
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