Department of Chemical and Biomolecular Engineering, University of Illinois, 600 S. Mathews Avenue, Urbana, IL 61801, USA.
J Control Release. 2012 Oct 28;163(2):130-5. doi: 10.1016/j.jconrel.2012.08.032. Epub 2012 Sep 7.
We have designed and evaluated a dual anticancer delivery system to provide combined gene therapy and chemotherapy. Double-walled microspheres consisting of a poly(d,l-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(lactic acid) (PLA) shell were fabricated via the precision particle fabrication (PPF) technique. We make use of the advantages of double-walled microspheres to deliver chitosan-DNA nanoparticles containing the gene encoding the p53 tumor suppressor protein (chi-p53) and/or doxorubicin (Dox), loaded in the shell and core phases, respectively. Different molecular weights of PLA were used to form the shell layer for each formulation. The microspheres were monodisperse with a mean diameter of 65 to 75 μm and uniform shell thickness of 8 to 17 μm. Blank and Dox-loaded microspheres typically exhibited a smooth surface with relatively few small pores, while chi-microspheres containing p53 nanoparticles, with and without Dox, presented rough and porous surfaces. The encapsulation efficiency of Dox was significantly higher when it was encapsulated alone compared to co-encapsulation with chi-p53 nanoparticles. The encapsulation efficiency of chi-p53 nanoparticles, on the other hand, was not affected by the presence of Dox. As desired, chi-p53 nanoparticles were released first, followed by simultaneous release of chi-p53 nanoparticles and Dox at a near zero-order rate. Thus, we have demonstrated that the PPF method is capable of producing double-walled microspheres and encapsulating dual agents for combined modality treatment, such as gene therapy and chemotherapy.
我们设计并评估了一种双重抗癌药物传递系统，以提供联合基因治疗和化疗。通过精密颗粒制造（PPF）技术制备了由聚（丙交酯-共-乙交酯）（PLGA）核和聚乳酸（PLA）壳组成的双层微球。我们利用双层微球的优势，分别在壳层和核相中递送壳聚糖-DNA 纳米颗粒，其中包含编码 p53 肿瘤抑制蛋白（chi-p53）的基因和/或多柔比星（Dox）。不同分子量的 PLA 用于形成每个配方的壳层。微球具有单分散性，平均直径为 65 至 75μm，壳层厚度均匀为 8 至 17μm。空白和载 Dox 的微球通常具有光滑的表面，相对较少的小孔，而含有 p53 纳米颗粒的 chi 微球，无论是否载有 Dox，表面均呈现粗糙多孔。与与 chi-p53 纳米颗粒共同包封相比，Dox 单独包封时的包封效率明显更高。另一方面，chi-p53 纳米颗粒的包封效率不受 Dox 存在的影响。如预期的那样，chi-p53 纳米颗粒首先释放，然后以近零级速率同时释放 chi-p53 纳米颗粒和 Dox。因此，我们已经证明 PPF 方法能够生产双层微球并封装双重药物用于联合治疗模式，如基因治疗和化疗。
