Chiappa Arianna, Fusari Alice, Uboldi Marco, Cavarzan Fabiana, Petrini Paola, Zema Lucia, Melocchi Alice, Briatico Vangosa Francesco
Dipartimento di Chimica, Materiali e Ingegneria Chimica "G. Natta", Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, Italy.
PhormulaMi Lab, Sezione di Tecnologia e Legislazione Farmaceutiche "Maria Edvige Sangalli", Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Giuseppe Colombo 71, 20133 Milano, Italy.
Gels. 2025 Jul 1;11(7):510. doi: 10.3390/gels11070510.
The incorporation of solid particles as a filler to a hydrogel is a strategy to modulate its properties for specific applications, or even to introduce new functionalities to the hydrogel itself. The efficacy of such a modification depends on the filler content and its interaction with the hydrogel matrix. In drug delivery applications, solid particles can be added to hydrogels to improve drug loading capacity, enable the inclusion of poorly soluble drugs, and modulate release kinetics. This work focuses on the case of alginate (ALG)-based hydrogels, obtained following an internal gelation procedure using CaCO as the Ca source and containing a high solid volume fraction (up to 50%) of metronidazole (MTZ), a drug with low water solubility, as a potential extrusion-based drug delivery system. The impact of the hydrogel precursor composition (ALG and MTZ content) on the rheological behavior of the filled hydrogel and precursor suspension were investigated, as well as the hydrogel stability and MTZ dissolution. In the absence of solid MTZ, the precursor solutions showed a slightly shear thinning behavior, more accentuated with the increase in ALG concentration. The addition of drugs exceeding the saturation concentration in the precursor suspension resulted in a substantial increase (about one order of magnitude) in the low-shear viscosity and, for the highest MTZ loadings, a yield stress. Despite the significant changes, precursor formulations retained their extrudability, as confirmed by both numerical estimates and experimental validation. MTZ particles did not affect the crosslinking of the precursors to form the hydrogel, but they did control its viscoelastic behavior. In unfilled hydrogels, the ALG concentration controls stability (from 70 h for the lowest concentration to 650 h for the highest) upon immersion in acetate buffer at pH 4.5, determining the MTZ release/hydrogel dissolution behavior. The correlations between composition and material properties offer a basis for building predictive models for fine-tuning their composition of highly filled hydrogel systems.
将固体颗粒作为填充剂加入水凝胶中，是一种调节其性能以用于特定应用的策略，甚至可以为水凝胶本身引入新功能。这种改性的效果取决于填充剂的含量及其与水凝胶基质的相互作用。在药物递送应用中，可将固体颗粒添加到水凝胶中，以提高药物载量、纳入难溶性药物并调节释放动力学。本研究聚焦于基于藻酸盐（ALG）的水凝胶，该水凝胶通过使用碳酸钙作为钙源的内部凝胶化程序制备而成，含有高固体体积分数（高达50%）的甲硝唑（MTZ，一种水溶性低的药物），作为潜在的基于挤压的药物递送系统。研究了水凝胶前体组成（ALG和MTZ含量）对填充水凝胶和前体悬浮液流变行为的影响，以及水凝胶稳定性和MTZ溶解情况。在没有固体MTZ的情况下，前体溶液表现出轻微的剪切变稀行为，随着ALG浓度的增加更加明显。在前体悬浮液中添加超过饱和浓度的药物会导致低剪切粘度大幅增加（约一个数量级），对于最高MTZ载量，还会产生屈服应力。尽管有显著变化，但前体制剂仍保持其可挤出性，这通过数值估计和实验验证得到证实。MTZ颗粒不影响前体交联形成水凝胶，但它们确实控制了其粘弹性行为。在未填充的水凝胶中，ALG浓度控制着在pH 4.5的醋酸盐缓冲液中浸泡时的稳定性（从最低浓度的70小时到最高浓度的650小时），决定了MTZ释放/水凝胶溶解行为。组成与材料性能之间的相关性为构建预测模型以微调其高填充水凝胶系统的组成提供了基础。
