Sweet Joe L, Pillay Viness, Choonara Yahya E
Webster Surgical Center, Tallahassee, Florida, USA.
Drug Deliv. 2007 Jul;14(5):309-18. doi: 10.1080/10717540701203067.
A 23 full factorial design was employed to evaluate and optimize the drug entrapment efficiency and in vitro drug release from PLGA microparticles encapsulated in a complex crosslinked alginate-pectinate matrix (polysphere). The independent formulation variables included the volume of internal and external phases, and concentration of PLGA. Surface morphology and internal structure of PLGA microparticles and polyspheres were examined by scanning electron microscopy which revealed spherical PLGA microparticles with highly porous surfaces that accounted for the rapid burst effect of this system. Texture analysis was used to profile the matrix resilience, tolerance, and energy absorbed. In vitro drug release was assessed in buffer media on PLGA microparticles and polyspheres. Polyspheres exhibited ideal zero-order release while PLGA microparticles had a burst effect followed by lag phase. Kinetic modeling of in vitro drug release data indicated that formulations were not highly dependent on polymeric erosion as a mechanism for drug release but rather diffusion. A close correlation existed between the matrix tolerance and energy absorbed. Formulations with decreased tolerance absorbed less energy, thus led to rapid surface erosion, lower matrix integrity and hence a burst effect. The converse was true for an increased matrix tolerance, which led to zero-order release supported by superior matrix integrity and a significantly reduced burst effect. The rat subcutaneous model validated in vitro release data and demonstrated that the polyspheres provided flexible yet superior rate-modulated drug delivery.
采用23全因子设计来评估和优化包裹在复合交联藻酸盐 - 果胶酸盐基质（多球体）中的PLGA微粒的药物包封效率和体外药物释放。独立的配方变量包括内相和外相的体积以及PLGA的浓度。通过扫描电子显微镜检查PLGA微粒和多球体的表面形态和内部结构，结果显示PLGA微粒呈球形，表面具有高度多孔性，这解释了该系统的快速突释效应。使用质地分析来描述基质的弹性、耐受性和吸收的能量。在缓冲介质中对PLGA微粒和多球体进行体外药物释放评估。多球体表现出理想的零级释放，而PLGA微粒则有一个突释效应，随后是滞后阶段。体外药物释放数据的动力学模型表明，制剂对作为药物释放机制的聚合物侵蚀的依赖性不高，而对扩散的依赖性较高。基质耐受性与吸收的能量之间存在密切相关性。耐受性降低的制剂吸收的能量较少，从而导致表面快速侵蚀、较低的基质完整性，进而产生突释效应。相反，基质耐受性增加时情况则相反，这导致了零级释放，其支持因素是卓越的基质完整性和显著降低的突释效应。大鼠皮下模型验证了体外释放数据，并表明多球体提供了灵活且卓越的速率调节药物递送。
