Fu K, Pack D W, Klibanov A M, Langer R
Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts, USA.
Pharm Res. 2000 Jan;17(1):100-6. doi: 10.1023/a:1007582911958.
In the past decade, biodegradable polymers have become the materials of choice for a variety of biomaterials applications. In particular, poly(lactic-co-glycolic acid) (PLGA) microspheres have been extensively studied for controlled-release drug delivery. However, degradation of the polymer generates acidic monomers, and acidification of the inner polymer environment is a central issue in the development of these devices for drug delivery.
To quantitatively determine the intrapolymer acidity, we entrapped pH-sensitive fluorescent dyes (conjugated to 10,000 Da dextrans) within the microspheres and imaged them with confocal fluorescence microscopy. The technique allows visualization of the spatial and temporal distribution of pH within the degrading microspheres (1).
Our experiments show the formation of a very acidic environment within the particles with the minimum pH as low as 1.5.
The images show a pH gradient, with the most acidic environment at the center of the spheres and higher pH near the edges, which is characteristic of diffusion-controlled release of the acidic degradation products.
在过去十年中，可生物降解聚合物已成为多种生物材料应用的首选材料。特别是，聚乳酸-乙醇酸共聚物（PLGA）微球已被广泛研究用于控释药物递送。然而，聚合物的降解会产生酸性单体，聚合物内部环境的酸化是这些药物递送装置开发中的一个核心问题。
为了定量测定聚合物内部的酸度，我们将pH敏感荧光染料（与10,000 Da葡聚糖偶联）包裹在微球内，并用共聚焦荧光显微镜对其成像。该技术能够可视化降解微球内pH的时空分布（1）。
我们的实验表明，颗粒内部形成了非常酸性的环境，最低pH值低至1.5。
图像显示出pH梯度，球体中心的酸性环境最强，边缘附近的pH值较高，这是酸性降解产物扩散控制释放的特征。
