Development and Evaluation of Nanomedicines (DEVANA), Faculty of Pharmacy, Albacete, Spain.
Instituto de Biomedicina (IB), Universidad de Castilla-La Mancha (UCLM), Albacete, 02008, Spain.
Drug Deliv Transl Res. 2024 Oct;14(10):2598-2614. doi: 10.1007/s13346-024-01641-7. Epub 2024 Jun 10.
The success of colon-targeted oral hybrid systems relies in the proper control over the release of the entrapped nanostructures at the colon. This work describes the design of hybrid systems for their colonic enzyme-triggered release. The hybrid systems were constituted by nanoemulsions, with adequate characteristics for the treatment of ulcerative colitis, included in a pectin hydrogel-like matrix. For that purpose, pectins with similar degrees of methylation (< 50%) and increasing degree of amidation, i.e. 0, 13 and 20%, were selected. Hybrid systems were formulated by a novel aggregation induced gelation method, using Ca, Ba or Zn as aggregating agents, as well as by a polyelectrolyte condensation approach, obtaining structures in the micrometric range (< 10 μm). Despite the resistance of pectins to the upper gastrointestinal tract stimuli, the analysis of the behaviour of the different prototypes showed that the non-covalent crosslinks that allow the formation of the hybrid structure may play a relevant role on the performance of the formulation.Our results indicated that the partial disassembling of the hybrid system's microstructure due to the intestinal conditions may facilitate the stimuli-triggered release of the nanoemulsions at the colon. More interestingly, the particle tracking experiments showed that the condensation process that occurs during the formation of the system may affect to the enzymatic degradation of pectin. In this sense, the effect of the high degree of amidation of pectin may be more prevalent as structural feature rather than as a promoter of the enzyme-triggered release.
结肠靶向口服混合系统的成功依赖于对纳米结构在结肠中释放的有效控制。本工作描述了用于结肠酶触发释放的混合系统的设计。混合系统由纳米乳液组成，具有治疗溃疡性结肠炎的适当特性，包含在果胶水凝胶样基质中。为此，选择了具有相似甲氧基化程度（<50%）和酰胺化程度增加的果胶，即 0、13 和 20%。通过一种新型的聚集诱导凝胶化方法（使用 Ca、Ba 或 Zn 作为聚集剂）和聚电解质缩合方法来制备混合系统，获得了微米级的结构（<10 μm）。尽管果胶能够抵抗上消化道刺激，但对不同原型的行为分析表明，允许形成混合结构的非共价交联可能在制剂的性能中发挥重要作用。我们的结果表明，由于肠道条件，混合系统的微观结构的部分解体可能有利于纳米乳液在结肠中的刺激触发释放。更有趣的是，颗粒跟踪实验表明，在系统形成过程中发生的缩合过程可能会影响果胶的酶降解。在这种意义上，果胶的高酰胺化程度的影响可能更倾向于作为结构特征，而不是作为酶触发释放的促进剂。
