Queen's University, Kingston, Ontario K7L 3N6, Canada.
J Pharm Sci. 2012 Feb;101(2):588-97. doi: 10.1002/jps.22782. Epub 2011 Oct 4.
The feasibility of generating an extended period of linear release of therapeutic proteins from photo-cross-linked, biodegradable elastomer monolithic devices in vitro has been previously demonstrated. The release is driven primarily by the osmotic pressure generated upon the dissolution of the encapsulated particles within the polymer. The osmotic pressure is provided by co-incorporation into the particle of trehalose as an osmotigen. Herein, we demonstrate that the release rate of a therapeutic protein, vascular endothelial growth factor (VEGF), by this osmotic pressure mechanism is the same in vivo as found in vitro. (125) I-VEGF was colyophilized with trehalose and serum albumin and distributed as particles throughout a photo-cross-linked elastomer composed of trimethylene carbonate, ε-caprolactone, and d,l-lactide. The release of VEGF from the device was monitored by measuring the decrease in radioactivity within the devices in vitro and within explanted devices that had been implanted subcutaneously in the dorsal area of Wistar rats. The released VEGF remained bioactive in vivo, inducing the formation of blood vessels that contained red blood cells. Furthermore, the released trehalose was well tolerated by the surrounding tissue.
先前已经证明，通过光交联可生物降解弹性体整体设备从封装的治疗性蛋白质中产生延长的线性释放的可行性。释放主要是由聚合物中封装的颗粒溶解时产生的渗透压驱动的。渗透压是通过在颗粒中共同掺入海藻糖作为渗透剂来提供的。在此，我们证明，通过这种渗透压机制释放治疗性蛋白质血管内皮生长因子（VEGF）的速率与体外发现的速率相同。（125）I-VEGF 与海藻糖和血清白蛋白共冻干，并分布在由三亚甲基碳酸酯、ε-己内酯和 d,l-丙交酯组成的光交联弹性体的颗粒中。通过测量体外设备和已植入 Wistar 大鼠背部皮下的植入设备内放射性的减少来监测 VEGF 从设备中的释放。释放的 VEGF 在体内仍然具有生物活性，诱导含有红细胞的血管形成。此外，释放的海藻糖被周围组织很好地耐受。
