Shoichet Molly S, Tator Charles H, Poon Peter, Kang Catherine, Baumann M Douglas
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Donnelly Center for Cellular and Biomolecular Research, Toronto, ON, M5S 3E1, Canada.
Prog Brain Res. 2007;161:385-92. doi: 10.1016/S0079-6123(06)61027-3.
Neuroprotective and neuroregenerative strategies for spinal cord injury repair are limited in part by poor delivery techniques. A novel drug delivery system is being developed in our laboratory that can provide localized release of therapeutically relevant molecules from an injectable hydrogel. Design criteria were established for the hydrogel to be--injectable, fast-gelling, biocompatible, biodegradable and able to release biologically active therapeutics when injected into the intrathecal space that surrounds the spinal cord. This novel way of localized drug delivery to the spinal cord was tested first with a collagen gel and then with a new hydrogel blend of hyaluronan and methylcellulose (HAMC). The underlying principle that this novel methodology is both safe and able to provide localized delivery was proven with a fast gelling collagen solution. Using a recombinant human epidermal growth factor, rhEGF, dispersed in collagen, we demonstrated localized release to the injured spinal cord. We extended this technology to other fast-gelling systems and found that HAMC was injectable due to the shear thinning property of hyaluronan (HA), biocompatible and had some therapeutic benefit when injected into the intrathecal space using a compression injury model in rats.
脊髓损伤修复的神经保护和神经再生策略在一定程度上受到递送技术不佳的限制。我们实验室正在开发一种新型药物递送系统，该系统可以从可注射水凝胶中实现治疗相关分子的局部释放。为该水凝胶确立了设计标准，使其具备可注射、快速凝胶化、生物相容性、可生物降解以及注入脊髓周围的鞘内空间时能够释放生物活性治疗药物的特性。这种向脊髓局部给药的新方法首先用胶原凝胶进行了测试，然后用透明质酸和甲基纤维素的新型水凝胶混合物（HAMC）进行了测试。一种快速凝胶化的胶原溶液证明了这种新方法既安全又能够实现局部给药的基本原理。我们使用分散在胶原中的重组人表皮生长因子rhEGF，证明了其能够向受损脊髓局部释放。我们将该技术扩展到其他快速凝胶化系统，发现由于透明质酸（HA）的剪切变稀特性，HAMC是可注射的，具有生物相容性，并且在使用大鼠压迫损伤模型注入鞘内空间时具有一定的治疗益处。
