Department of Chemical Engineering, University of Toledo, Toledo, Ohio 43606, United States.
Langmuir. 2024 Jun 11;40(23):11947-11958. doi: 10.1021/acs.langmuir.4c00297. Epub 2024 May 28.
Calcium alginate (Ca/alginate) gel beads find use in diverse applications, ranging from drug delivery and tissue engineering to bioprocessing, food formulation, and agriculture. Unless modified, however, these gels have limited stability in alkaline media (including phosphate buffers), and their high solute permeability limits their ability to efficiently encapsulate and slowly release water-soluble small molecules. Here, we show how these limitations can be addressed by mixing the alginate solutions used in the bead preparation with the nontoxic anionic polymer polyphosphate (PP). Upon complexing Ca ions, PP undergoes complex coacervation (i.e., liquid/liquid phase separation into a Ca/PP-rich coacervate phase and a dilute supernatant phase). At lower PP concentrations, the Ca/PP coacervate appears to simply remain dispersed within the beads. Though its presence makes the beads more stable in alkaline media (phosphate-buffered saline and seawater), it has little impact on the bead stiffness, morphology, and (at least in the absence of substantial payload/coacervate association) encapsulation and release properties. When the PP concentrations exceed a critical value, however, Ca/PP coacervation within the gelling Ca/alginate beads collapses the resulting beads into more compact, interpenetrating polymer networks. Besides their enhanced stability to alkaline environments, these hybrid beads exhibit irregular morphologies with wrinkled and dimpled surface structures and macroscopic (closed) internal pores, and their collapse into these polymer-rich networks also makes them significantly stiffer than their PP-free counterparts. Crucially, these beads also exhibit a much lower solute permeability, which enables highly efficient encapsulation and multiday release of water-soluble small molecules (with the beads encapsulating >90% of the added model payload and sustaining its release over 3-5 d). Collectively, these findings provide a mild and simple (single-step) pathway to generating ionically cross-linked alginate beads with significantly enhanced stability, encapsulation efficiency, and sustained release.
海藻酸钙（Ca/alginate）凝胶珠在药物输送、组织工程、生物加工、食品配方和农业等多个领域都有应用。然而，如果不进行修饰，这些凝胶在碱性介质（包括磷酸盐缓冲液）中的稳定性有限，而且其高溶质渗透性限制了它们有效封装和缓慢释放水溶性小分子的能力。在这里，我们展示了如何通过混合在珠粒制备中使用的藻酸盐溶液与无毒阴离子聚合物多磷酸盐（PP）来解决这些限制。在与 Ca 离子络合后，PP 会发生复杂共凝聚（即，液体/液体相分离为富含 Ca/PP 的凝聚相和稀的上清相）。在较低的 PP 浓度下，Ca/PP 凝聚物似乎简单地分散在珠粒内。尽管它的存在使珠粒在碱性介质（磷酸盐缓冲盐水和海水）中更稳定，但对珠粒的硬度、形态以及（至少在没有大量负载物/凝聚物结合的情况下）封装和释放性能影响不大。然而，当 PP 浓度超过临界值时，Ca/alginate 凝胶珠中的 Ca/PP 共凝聚会使珠粒塌陷成更紧凑的互穿聚合物网络。除了增强对碱性环境的稳定性外，这些杂化珠粒还具有不规则的形态，表面结构有皱纹和凹陷，宏观（封闭）内部孔，并且它们塌陷成这些富含聚合物的网络也使它们比没有 PP 的珠粒硬得多。至关重要的是，这些珠粒还表现出更低的溶质渗透性，这使得它们能够高效封装和多天释放水溶性小分子（珠粒封装了超过 90%的添加模型负载物，并在 3-5 天内持续释放）。总的来说，这些发现提供了一种温和简单（单步）的途径，可生成离子交联的海藻酸钙珠粒，具有显著增强的稳定性、封装效率和持续释放。
