Curley John, Hasan Mohammad Raquibul, Larson Jacob, Brooks Benjamin D, Liu Qianhui, Jain Tanmay, Joy Abraham, Brooks Amanda E
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, USA.
Department of Industrial and Manufacturing Engineering, North Dakota State University, Fargo, ND 58105, USA.
Polymers (Basel). 2016 Jun 30;8(7):247. doi: 10.3390/polym8070247.
With the rising tide of antibiotic resistant bacteria, extending the longevity of the current antibiotic arsenal is becoming a necessity. Developing local, controlled release antibiotic strategies, particularly for difficult to penetrate tissues such as bone, may prove to be a better alternative. Previous efforts to develop an osteoconductive local antibiotic release device for bone were created as solid molded composites; however, intimate contact with host bone was found to be critical to support host bone regrowth; thus, an osteocondconductive antibiotic releasing bone void filling putty was developed. Furthermore, a controlled releasing polymer matrix was refined using pendant-functionalized diols to provide tailorable pharmacokinetics. In vitro pharmacokinetic and bioactivity profiles were compared for a putty formulation with an analogous composition as its molded counterpart as well as four new pendant-functionalized polymers. A best-fit analysis of polymer composition in either small cylindrical disks or larger spheres revealed that the new pendant-functionalized polymers appear to release vancomycin via both diffusion and erosion regardless of the geometry of the putty. In silico simulations, a valuable technique for diffusion mediated controlled release models, will be used to confirm and optimize this property.
随着抗生素耐药菌的不断增加，延长现有抗生素库的使用寿命变得十分必要。开发局部控释抗生素策略，尤其是针对诸如骨骼等难以渗透的组织，可能被证明是一种更好的选择。先前开发用于骨骼的骨传导性局部抗生素释放装置是作为固体模塑复合材料制成的；然而，发现与宿主骨的紧密接触对于支持宿主骨再生至关重要；因此，开发了一种骨传导性抗生素释放骨缺损填充腻子。此外，使用侧链官能化二醇对控释聚合物基质进行了优化，以提供可定制的药代动力学。对一种具有与其模塑对应物类似组成的腻子配方以及四种新的侧链官能化聚合物进行了体外药代动力学和生物活性分析。对小圆柱盘或大球体中聚合物组成的最佳拟合分析表明，无论腻子的几何形状如何，新的侧链官能化聚合物似乎都通过扩散和侵蚀两种方式释放万古霉素。计算机模拟是扩散介导控释模型的一种有价值的技术，将用于确认和优化这一特性。
