Department of Chemical Engineering, Monash University, Clayton 3800, VIC, Australia.
Eur J Pharm Sci. 2010 Mar 18;39(5):412-20. doi: 10.1016/j.ejps.2010.01.011. Epub 2010 Feb 1.
DNA vaccines or proteins are capable of inducing specific immunity; however, the translation to the clinic has generally been problematic, primarily due to the reduced magnitude of immune response and poor pharmacokinetics. Herein we demonstrate a composite microsphere formulation, composed of mesoporous silica spheres (MPS) and poly(D,L-lactide-co-glycolide) (PLGA), enables the controlled delivery of a prime-boost vaccine via the encapsulation of plasmid DNA (pDNA) and protein in different compartments. Method with modified dual-concentric-feeding needles attached to a 40 kHz ultrasonic atomizer was studied. These needles focus the flow of two different solutions, which passed through the ultrasonic atomizer. The process synthesis parameters, which are important to the scale-up of composite microspheres, were also studied. These parameters include polymer concentration, feed flowrate, and volumetric ratio of polymer and pDNA-PEI/MPS-BSA. This fabrication technique produced composite microspheres with mean D[4,3] ranging from 6 to 34 microm, depending upon the microsphere preparation. The resultant physical morphology of composite microspheres was largely influenced by the volumetric ratio of pDNA-PEI/MPS-BSA to polymer, and this was due to the precipitation of MPS at the surface of the microspheres. The encapsulation efficiencies were predominantly in the range of 93-98% for pDNA and 46-68% for MPS. In the in vitro studies, the pDNA and protein showed different release kinetics in a 40 day time frame. The dual-concentric-feeding in ultrasonic atomization was shown to have excellent reproducibility. It was concluded that this fabrication technique is an effective method to prepare formulations containing a heterologous prime-boost vaccine in a single delivery system.
DNA 疫苗或蛋白质能够诱导特异性免疫；然而，向临床的转化通常存在问题，主要是由于免疫反应的幅度降低和药代动力学不佳。本文中，我们展示了一种复合微球制剂，由介孔硅球（MPS）和聚（D，L-乳酸-共-乙醇酸）（PLGA）组成，通过将质粒 DNA（pDNA）和蛋白质封装在不同的隔室中，实现了一种初免-加强疫苗的控制释放。方法是使用附有改良双同心进料针的 40 kHz 超声雾化器进行研究。这些针将两种不同溶液的流动聚焦在一起，这两种溶液通过超声雾化器。还研究了对复合微球放大很重要的过程合成参数，包括聚合物浓度、进料流速以及聚合物和 pDNA-PEI/MPS-BSA 的体积比。该制造技术生产的复合微球的平均 D[4,3]范围为 6 至 34 微米，具体取决于微球的制备。复合微球的最终物理形态主要受 pDNA-PEI/MPS-BSA 与聚合物的体积比影响，这是由于 MPS 在微球表面沉淀。包封效率主要在 pDNA 的 93-98%和 MPS 的 46-68%范围内。在体外研究中，pDNA 和蛋白质在 40 天的时间内显示出不同的释放动力学。超声雾化中的双同心进料显示出出色的重现性。结论是，这种制造技术是在单一给药系统中制备含有异源初免-加强疫苗的制剂的有效方法。
