Department of Biomedical Sciences, School of Infection, Inflammation, & Immunology, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
The Microbiome Treatment Centre, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
J Control Release. 2024 Nov;375:495-512. doi: 10.1016/j.jconrel.2024.09.021. Epub 2024 Sep 20.
The process of microencapsulation and the development of microparticle-based drug formulations have gained increased pharmaceutical interest, particularly for drug delivery and bacterial-encapsulation purposes for probiotic delivery. Existing studies have examined microcomposite (MC) responses to gastrointestinal (GI) conditions with the aim of controlling disintegration, and thus release, across the small and large bowel. However, the delivery of MCs which remain intact, without degrading, could act as bacterial growth scaffolds or materials providing a prebiotic support, conferring potentially beneficial GI health properties. This present study employs prilling as a method to produce a portfolio of MCs using a variety of biopolymers (alginate, chitosan, pectin and gellan gum) with a range of MC diameters and density compositions. Fluorescent probes are co-encapsulated within each MC to enable flow-cytometry directed release profile assessments following exposure to chemical simulated gastric and intestinal digestion conditions. We observe that MC size, gel-strength, density, and biopolymer material all influence response to gastric and intestinal conditions. Gellan gum (GG) MCs demonstrated complete resistance to disintegration throughout GI-simulation in the stomach and small intestine. Considering these MCs could reach the colon intact, we then examined how such MCs, doped with prebiotic growth supporting carboxymethyl cellulose (CMC) polymers, could impact microbial communities using a bioreactor model of the colonic microbiome. Following supplementation with GGCMC MCs, mucosal bacterial diversity (using 16 s rRNA sequencing and Shannon entropy and observed feature diversity metrics) and taxonomic composition changes were observed. Concentrations of short chain fatty acid (SCFA) metabolites were also found to be altered. This is the first study to comprehensivelyexamine how MC physicochemistry can be manipulated to tailor MCs to have the desired GI release performance and subsequently, how GI-resistant MCs could have influential microbial altering properties and be adopted in novel prebiotic strategies.
微胶囊化过程和基于微粒的药物制剂的开发引起了制药行业的浓厚兴趣，特别是在药物传递和益生菌传递的细菌包封方面。现有研究已经检查了微复合材料（MC）对胃肠道（GI）条件的反应，目的是控制在小肠和大肠中的崩解和释放。然而，保持完整而不降解的 MC 可以作为细菌生长支架或提供益生元支持的材料，赋予潜在有益的 GI 健康特性。本研究采用制粒作为一种方法，使用各种生物聚合物（藻酸盐、壳聚糖、果胶和结冷胶）生产一系列 MC，其 MC 直径和密度组成范围广泛。将荧光探针共同包封在每个 MC 中，以便在暴露于化学模拟的胃和肠消化条件后，通过流式细胞术进行释放曲线评估。我们观察到 MC 尺寸、凝胶强度、密度和生物聚合物材料都影响对胃和肠条件的反应。在胃和小肠的 GI 模拟中，结冷胶（GG）MC 完全抵抗崩解。考虑到这些 MC 可以完整地到达结肠，我们然后研究了掺杂有支持益生元生长的羧甲基纤维素（CMC）聚合物的此类 MC 如何通过结肠微生物组的生物反应器模型影响微生物群落。用 GGCMC MC 补充后，观察到粘膜细菌多样性（使用 16s rRNA 测序和香农熵和观察到的特征多样性指标）和分类组成发生变化。短链脂肪酸（SCFA）代谢物的浓度也发现发生了变化。这是第一项全面研究 MC 物理化学性质如何被操纵以定制 MC 以具有所需的 GI 释放性能的研究，以及随后如何 GI 抗性 MC 可以具有有影响力的微生物改变特性并被采用于新型的益生元策略。
