Vaz Cláudia M, van Doeveren Patrick F N M, Dias Gustavo R, Reis Rui L, Cunha António M
Department of Polymer Engineering, University of Minho, Campus de Azurém, 4800-058 Guimarães, Portugal.
Macromol Biosci. 2004 Aug 9;4(8):795-801. doi: 10.1002/mabi.200300060.
The aim of this study was to design new soy protein-based bi-layered co-injection moulded matrix systems aimed to achieve controlled drug delivery. The devices consisted of a drug-free outer layer (skin) and a drug-containing core. The systems overcame the inherent disadvantage of non-linear release associated with diffusion-controlled single-layer matrix devices by providing additional releasing area with time to compensate for the decreasing release rate. As expected, the bi-layer devices presented a significant decrease in drug release rate when compared with a correspondent single layer matrix system. The skin thickness and the degree of crosslinking of the core appeared to be very important tools to tailor the release patterns. Furthermore, due to the amphoteric nature of the soy protein, the developed devices evidenced a pH-dependent behaviour. The mechanisms of drug release were also elucidated at two different pH values: i) pH 5.0, near the isoelectric point of soy (low matrix solubility); and ii) pH 7.4, physiological pH (high matrix solubility). Consequently, changing the release medium from pH 5.0 to pH 7.4 after two hours, led to an abrupt increase in drug release and the devices presented a typical controlled drug delivery profile: slow release/fast release. These evidences may provide for the development of individual systems with different release onsets that in combination may exhibit drug releases at predetermined times in a pre-programmed way. Another possibility is the production of three-layer devices presenting bimodal release profiles (fast release/slow release/fast release) by similar technologies. Scanning electron micrograph of a developed bi-layer device.
本研究的目的是设计新型大豆蛋白基双层共注塑成型基质系统，以实现药物的控释。这些装置由无药外层（皮层）和含药核心组成。该系统克服了与扩散控制的单层基质装置相关的非线性释放的固有缺点，通过随着时间提供额外的释放面积来补偿释放速率的降低。正如预期的那样，与相应的单层基质系统相比，双层装置的药物释放速率显著降低。皮层厚度和核心的交联程度似乎是调整释放模式的非常重要的因素。此外，由于大豆蛋白的两性性质，所开发的装置表现出pH依赖性行为。还在两个不同的pH值下阐明了药物释放机制：i）pH 5.0，接近大豆的等电点（低基质溶解度）；ii）pH 7.4，生理pH值（高基质溶解度）。因此，两小时后将释放介质从pH 5.0变为pH 7.4，导致药物释放突然增加，并且这些装置呈现出典型的控释曲线：缓释/速释。这些证据可为开发具有不同释放起始点的个体系统提供依据，这些系统组合起来可以以预编程的方式在预定时间呈现药物释放。另一种可能性是通过类似技术生产具有双峰释放曲线（速释/缓释/速释）的三层装置。所开发的双层装置的扫描电子显微镜照片。
