PDF(Pubmed)
Abstract：
Protein therapeutics have become increasingly popular for the treatment of a variety of diseases owing to their specificity to targets of interest. However, challenges associated with them have limited their use for a range of ailments, including the limited options available for local controlled delivery. To address this challenge, degradable hydrogel microparticles, or microgels, loaded with model biocargoes were created with tunable release profiles or triggered burst release using chemistries responsive to endogenous or exogeneous stimuli, respectively. Specifically, microfluidic flow-focusing was utilized to form homogenous microgels with different spontaneous click chemistries that afforded degradation either in response to redox environments for sustained cargo release or light for on-demand cargo release. The resulting microgels were an appropriate size to remain localized within tissues upon injection and were easily passed through a needle relevant for injection, providing means for localized delivery. Release of a model biopolymer was observed over the course of several weeks for redox-responsive formulations or triggered for immediate release from the light-responsive formulation. Overall, we demonstrate the ability of microgels to be formulated with different materials chemistries to achieve various therapeutic release modalities, providing new tools for creation of more complex protein release profiles to improve therapeutic regimens.
摘要：
蛋白质治疗剂由于其对目标靶标的特异性而变得越来越流行用于治疗多种疾病。然而,与它们相关的挑战限制了它们在一系列疾病中的使用，包括可用于本地控制下交付的有限选择。为了应对这一挑战，可降解水凝胶微粒，或者微凝胶，使用响应于内源性或外源性刺激的化学物质，以可调的释放曲线或触发的爆发释放创建模型生物碳，分别。具体来说,微流体流动聚焦用于形成具有不同自发点击化学的均质微凝胶,其响应于用于持续货物释放的氧化还原环境或用于按需货物释放的光而提供降解。所得到的微凝胶具有适当的尺寸以在注射时保持局部在组织内,并且容易地通过与注射相关的针。提供本地化交付的手段。对于氧化还原响应性制剂,在数周的过程中观察到模型生物聚合物的释放,或触发从光响应性制剂中立即释放。总的来说,我们证明了微凝胶与不同材料化学制剂的能力，以实现各种治疗释放方式，为创建更复杂的蛋白质释放曲线提供新的工具，以改善治疗方案。
