Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen, Denmark.
J Control Release. 2011 Nov 30;156(1):11-20. doi: 10.1016/j.jconrel.2011.07.013. Epub 2011 Jul 20.
Injectable cell scaffolds play a dual role in tissue engineering by supporting cellular functions and delivering bioactive molecules. The present study aimed at developing biodegradable nanocomposite microparticles with sustained drug delivery properties thus potentially being suitable for autologous stem cell therapy. Semi-crystalline poly(l-lactide/dl-lactide) (PLDL70) and poly(l-lactide-co-glycolide) (PLGA85) were used to prepare nanoparticles by the double emulsion method. Uniform and spherical nanoparticles were obtained at an average size of 270-300 nm. The thrombin receptor activator peptide-6 (TRAP-6) was successfully loaded in PLDL70 and PLGA85 nanoparticles. During the 30 days' release, PLDL70 nanoparticles showed sustainable release with only 30% TRAP-6 released within the first 15 days, while almost 80% TRAP-6 was released from PLGA85 nanoparticles during the same time interval. The release mechanism was found to depend on the crystallinity and composition of the nanoparticles. Subsequently, mPEG-PLGA nanocomposite microparticles containing PLDL70 nanoparticles were produced by the ultrasonic atomization method and evaluated to successfully preserve the intrinsic particulate properties and the sustainable release profile, which was identical to that of the nanoparticles. Good cell adhesion of the human fibroblasts onto the nanocomposite microparticles was observed, indicating the desired cell biocompatibility. The presented results thus demonstrate the development of nanocomposite microparticles tailored for sustainable drug release for application as injectable cell scaffolds.
可注射细胞支架在组织工程中具有双重作用，既能支持细胞功能，又能输送生物活性分子。本研究旨在开发具有持续药物释放性能的可生物降解纳米复合微球，从而有可能适用于自体干细胞治疗。半结晶聚（L-丙交酯/DL-丙交酯）（PLDL70）和聚（L-丙交酯-共-乙交酯）（PLGA85）被用来通过双乳液法制备纳米颗粒。在平均粒径为 270-300nm 时，可以得到均匀和球形的纳米颗粒。血栓酶受体激活肽-6（TRAP-6）成功地装载在 PLDL70 和 PLGA85 纳米颗粒中。在 30 天的释放过程中，PLDL70 纳米颗粒表现出持续释放，在前 15 天内仅释放了 30%的 TRAP-6，而在相同的时间间隔内，PLGA85 纳米颗粒释放了近 80%的 TRAP-6。释放机制被发现取决于纳米颗粒的结晶度和组成。随后，通过超声雾化法制备了含有 PLDL70 纳米颗粒的 mPEG-PLGA 纳米复合微球，并对其进行了评价，成功地保留了纳米颗粒的固有颗粒特性和持续释放特性，与纳米颗粒的特性相同。观察到人成纤维细胞良好地黏附在纳米复合微球上，表明其具有良好的细胞生物相容性。因此，研究结果表明，开发了用于持续药物释放的纳米复合微球，可作为可注射细胞支架。
