Poetz Katie L, Mohammed Halimatu S, Shipp Devon A
†Department of Chemistry and Biomolecular Science and ‡Center for Advanced Materials Processing, Clarkson University, Potsdam, New York 13699-5810, United States.
Biomacromolecules. 2015 May 11;16(5):1650-9. doi: 10.1021/acs.biomac.5b00280. Epub 2015 Apr 20.
Surface eroding and semicrystalline polyanhydrides, with tunable erosion times and drug delivery pharmacokinetics largely dictated by erosion, are produced easily with thiol-ene "click" polymerization. This strategy yields both linear and cross-linked network polyanhydrides that are readily and fully cured within minutes using photoinitiation, can contain up to 60% crystallinity, and have tensile moduli up to 25 MPa for the compositions studied. Since they readily undergo hydrolysis and exhibit the oft-preferred surface erosion mechanism, they may be particularly useful in drug delivery applications. The polyanhydrides were degraded under pseudophysiological conditions and cylindrical samples (10 mm diameter × 5 mm height) were completely degraded within ∼10 days, with the mass-time profile being linear for much of this time after a ∼24 h induction period. Drug release studies, using lidocaine as a model, showed pharmacokinetics that displayed a muted burst release in the early stages of erosion, but then a delayed release profile that is closely correlated to the erosion kinetics. Furthermore, cytotoxicity studies of the linear and cross-linked semicrystalline polyanhydrides, and degradation products, against fibroblast cells indicate that the materials have good cytocompatibility. Overall, cells treated with up to 2500 mg/L of the semicrystalline polyanhydrides and degradation products show >90% human dermal fibroblast adult (HDFa) cell viability indicative of good cytocompatibility.
通过硫醇-烯“点击”聚合反应可以轻松制备出表面侵蚀型半结晶聚酸酐，其侵蚀时间和药物递送药代动力学具有可调节性，且很大程度上由侵蚀作用决定。该策略可生成线性和交联网络聚酸酐，使用光引发在几分钟内即可快速且完全固化，结晶度可达60%，对于所研究的组合物，其拉伸模量高达25MPa。由于它们易于发生水解并呈现出常被青睐的表面侵蚀机制，因此在药物递送应用中可能特别有用。聚酸酐在伪生理条件下会降解，圆柱形样品（直径10mm×高5mm）在约10天内完全降解，在约24小时的诱导期后，质量-时间曲线在这段时间的大部分时间内呈线性。以利多卡因为模型的药物释放研究表明，药代动力学在侵蚀早期呈现出温和的突释，但随后是与侵蚀动力学密切相关的延迟释放曲线。此外，线性和交联半结晶聚酸酐及其降解产物对成纤维细胞的细胞毒性研究表明，这些材料具有良好的细胞相容性。总体而言，用高达2500mg/L的半结晶聚酸酐及其降解产物处理的细胞显示，人皮肤成纤维细胞（HDFa）的细胞活力>90%，表明具有良好的细胞相容性。
