Department of Chemical Engineering, Queen's University, 99 University Ave., Kingston, Ontario, Canada.
Department of Chemical Engineering, Queen's University, 99 University Ave., Kingston, Ontario, Canada.
J Pharm Sci. 2021 Jun;110(6):2472-2478. doi: 10.1016/j.xphs.2021.01.006. Epub 2021 Jan 13.
Alginate solutions crosslink into microspheres in calcium alginate, enabling the encapsulation and subsequent release of biological macromolecules and drugs. However, release from calcium alginate into PBS is relatively fast because it will decrosslink the gel relatively quickly. In this research, FITC-dextran (MW 10 kDa) was encapsulated in 2% (w/v) calcium alginate microspheres by electrospraying. The resulting microspheres (diameter = 247 ± 13 μm) were then layered with thin polyelectrolyte films of hyaluronic acid (HA) and poly-l-lysine (PLL) to attempt to slow the diffusion of FITC-dextran out of the microspheres and the coating parameters were modified to modulate diffusion and release. Increasing the concentration of FITC-dextran encapsulated in the microspheres resulted in an increase in its release over time into PBS. Crosslinking PLL/HA layers on the microspheres did not decrease the in vitro release rates of encapsulated FITC-dextran into PBS. Increasing the number of layers on the microspheres from 3 to 5 layers significantly decreased the amount of encapsulated FITC-dextran released. However, increasing the number of layers to 7 did not further sustain the release of FITC-dextran, likely because these microspheres collapsed to a smaller size during the coating procedure, resulting in release controlled by both diffusion and swelling. Multiple layers of PLL and HA provided a robust mechanism to sustain and control release of large molecules from calcium alginate.
海藻酸钠溶液在海藻酸钙中交联形成微球,从而能够包封生物大分子和药物,并随后进行释放。然而,由于凝胶会相对较快地解交联,因此从海藻酸钙到 PBS 的释放相对较快。在这项研究中,通过电喷雾将 FITC-葡聚糖(MW 10 kDa)封装在 2%(w/v)的海藻酸钠微球中。然后,将所得微球(直径=247±13μm)用透明质酸(HA)和聚-l-赖氨酸(PLL)的薄聚电解质层进行层压,以尝试减缓 FITC-葡聚糖从微球中的扩散,并且对涂层参数进行了修改以调节扩散和释放。随着微球中包封的 FITC-葡聚糖浓度的增加,其在 PBS 中的释放时间也随之增加。交联 PLL/HA 层不会降低包封的 FITC-葡聚糖在 PBS 中的体外释放率。将微球上的层从 3 层增加到 5 层,显著减少了释放的包封 FITC-葡聚糖的量。但是,将层数增加到 7 层并不能进一步维持 FITC-葡聚糖的释放,这可能是因为这些微球在涂层过程中坍塌到较小的尺寸,导致释放受到扩散和溶胀的共同控制。多层 PLL 和 HA 提供了一种稳健的机制,可以持续控制和释放海藻酸钙中的大分子。