Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano (SA), Italy.
Molecules. 2020 Mar 4;25(5):1140. doi: 10.3390/molecules25051140.
The aim of this research was to verify the application of alginate in combination with Ca and Zn ions to produce a floating and prolonged release system for the oral administration of prednisolone. Hollow and floating gel-beads were designed using prilling/ionotropic gelation as the microencapsulation technique, zinc acetate in the gelling solution as the alginate external crosslinker, and calcium carbonate in the feed as the internal crosslinking agent able to generate gas when in contact with the acidic zinc acetate solution. To achieve this goal, drug/alginate solutions were opportunely combined with different amounts of calcium carbonate. The effect of the addition of calcium carbonate into the feed solution on buoyancy, encapsulation efficiency, morphology, size distribution, as well as in vitro drug release profile of the alginate particles was studied. Moreover, the ability of the floating beads to modulate in vivo the anti-inflammatory response was assayed using the carrageenan-induced acute oedema in rat paw. The proposed strategy allowed obtaining alginate beads with extremely high encapsulation efficiency values (up to 94%) and a very porous inner matrix conferring buoyancy in vitro in simulated gastric fluid up to 5 h. Moreover, in vivo, the best formulation, F4, resulted in the ability to prolong the anti-inflammatory effect up to 15 h compared with raw prednisolone.
本研究旨在验证海藻酸盐与 Ca 和 Zn 离子结合应用于制备泼尼松龙口服的漂浮和缓释系统。采用成粒/离子凝胶化作为微囊化技术，使用醋酸锌凝胶溶液中的醋酸锌作为海藻酸盐外部交联剂，以及饲料中的碳酸钙作为内部交联剂，在与酸性醋酸锌溶液接触时能产生气体，设计了空心和漂浮凝胶珠。为了实现这一目标，药物/海藻酸盐溶液与不同量的碳酸钙进行了适当的组合。研究了碳酸钙添加到饲料溶液中对海藻酸盐颗粒的漂浮性、包封效率、形态、粒径分布以及体外药物释放特性的影响。此外，还使用角叉菜胶诱导的大鼠爪急性水肿来测定漂浮珠在体内调节抗炎反应的能力。所提出的策略允许获得具有极高包封效率值（高达 94%）的海藻酸盐珠，并且非常多孔的内部基质在模拟胃液中赋予体外漂浮性长达 5 小时。此外，在体内，最佳配方 F4 与原泼尼松龙相比，能够将抗炎作用延长至 15 小时。
