Biodegradable Polymerized Simvastatin

描述：合成的可降解聚合物通常用于药物输送和帮助组织再生。药物通常被包裹在材料中，以便随后以扩散和/或降解为媒介释放。然而，封装的限制包括有限的有效载荷和过早耗尽递送系统的可能性。为了延长释放时间，药物被连接到聚合物上。药物可以通过连接物连接到聚合物上，然后在裂解后释放分子，或者在合成过程中将药物结合到聚合物主干中。该项目的首要目标是开发和表征一种使用药物分子合成的聚合物，在目前的情况下是辛伐他汀，作为单体。工作假设是辛伐他汀的结构，在前药中含有内酯部分，服从开环聚合。因此，聚合的辛伐他汀可以加工成薄膜，通过水解降解以释放生物活性的辛伐他汀分子，这些分子除了具有众所周知的降血脂作用外，还具有成骨、抗炎和血管生成特性。目标1将开发和表征一种可降解的聚合形式的辛伐他汀。关于这一目标，假设该聚合物可以加工成释放辛伐他汀的可生物降解的薄膜。目的2研究辛伐他汀聚合膜在大鼠颅骨上种植模型中体内降解以促进成骨的作用。据推测，随着聚合物的降解，生物活性辛伐他汀被释放，以促进局部骨形成。如果为这项探索/发展奖提出的原则证明研究取得成功，聚合物可能被制造成各种物理形式(例如微球和组织工程支架)，以利用辛伐他汀在骨骼和其他组织应用的多效性效应，以及可能适用于他汀类药物家族其他成员的方法。

DESCRIPTION: Synthetic degradable polymers are commonly used for drug delivery and to aid in tissue regeneration. Drugs are routinely encapsulated in the material for subsequent diffusion- and/or degradation-mediated release. Limitations with encapsulation, however, include limited payload and the potential for premature exhaustion of the delivery system. To prolong release, drugs have been conjugated to polymers. Drug can be attached to the polymer via a linker that subsequently releases the molecule following cleavage, or it can be incorporated into the polymeric backbone during synthesis. The overarching goal of this project is to develop and characterize a polymer synthesized using drug molecules, in the present case simvastatin, as monomers. The working hypothesis is that the structure of simvastatin, with a lactone moiety in the prodrug, is amenable to ring-opening polymerization. As such, polymerized simvastatin could then be processed into films that degrade by hydrolysis to release bioactive simvastatin molecules, which have osteogenic, anti-inflammatory, and angiogenic properties in addition to their well-known known hypolipidemic effects. Aim 1 will develop and characterize a degradable, polymerized form of simvastatin. With respect to this objective, it is hypothesized that the polymer can be processed into biodegradable films that release simvastatin. Aim 2 will investigate whether polymerized films of simvastatin degrade in vivo to stimulate osteogenesis in a rodent supracalvarial implantation model. It is hypothesized that, as the polymer degrades, bioactive simvastatin is released to enhance local bone formation. If the proof-of-principle studies proposed for this Exploratory/Developmental Award are successful, the polymer may be fabricated into a variety of physical forms (e.g., microspheres and tissue engineering scaffolds) to exploit the pleiotropic effects of simvastatin for bone and other tissue applications, as well as the methods potentially being applicable to other members of the statin family.