Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, 164 College Street, Room 407, Toronto, ON M5S 3G9, Canada.
Department of Surgery, University of Toronto, 160 College Street, Room 1006, Toronto, ON M5S 3E1, Canada.
J Control Release. 2013 Nov 28;172(1):1-11. doi: 10.1016/j.jconrel.2013.07.032. Epub 2013 Aug 9.
Stroke is a leading cause of disability with no effective regenerative treatment. One promising strategy for achieving tissue repair involves the stimulation of endogenous neural stem/progenitor cells through sequential delivery of epidermal growth factor (EGF) followed by erythropoietin (EPO). Yet currently available delivery strategies such as intracerebroventricular (ICV) infusion cause significant tissue damage. We designed a novel delivery system that circumvents the blood brain barrier and directly releases growth factors to the brain. Sequential release of the two growth factors is a key in eliciting tissue repair. To control release, we encapsulate pegylated EGF (EGF-PEG) in poly(lactic-co-glycolic acid) (PLGA) nanoparticles and EPO in biphasic microparticles comprised of a PLGA core and a poly(sebacic acid) coating. EGF-PEG and EPO polymeric particles are dispersed in a hyaluronan methylcellulose (HAMC) hydrogel which spatially confines the particles and attenuates the inflammatory response of brain tissue. Our composite-mediated, sequential delivery of EGF-PEG and EPO leads to tissue repair in a mouse stroke model and minimizes damage compared to ICV infusion.
中风是导致残疾的主要原因，目前尚无有效的再生治疗方法。一种有前途的组织修复策略是通过顺序递增强表皮生长因子（EGF）和促红细胞生成素（EPO）来刺激内源性神经干细胞/祖细胞。然而，目前可用的递药策略，如脑室内（ICV）输注，会导致明显的组织损伤。我们设计了一种新型的递药系统，可绕过血脑屏障并将生长因子直接递送到大脑。两种生长因子的顺序释放是引发组织修复的关键。为了控制释放，我们将聚乙二醇化 EGF（EGF-PEG）包封在聚（乳酸-共-乙醇酸）（PLGA）纳米颗粒中，将 EPO 包封在由 PLGA 核和聚（癸二酸）涂层组成的双相微颗粒中。EGF-PEG 和 EPO 聚合物颗粒分散在透明质酸甲基纤维素（HAMC）水凝胶中，该水凝胶可将颗粒空间限制并减轻脑组织的炎症反应。我们的复合介导、顺序递药 EGF-PEG 和 EPO 可导致小鼠中风模型中的组织修复，并与 ICV 输注相比最小化损伤。
