Yaxin Jia, Jiajia Gengji, Tao Gong, Zhirong Zhang, Li Deng
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Baicalin (BA) has demonstrated anti-inflammatory benefits for inflammatory bowel disease, and the objective of this scholarly work is to address the challenges associated with the poor aqueous solubility and diminished oral bioavailability of the compound in question, thereby offering an innovative therapeutic approach for the management of ulcerative colitis.</p><p><strong>Methods: </strong>We developed a baicalin-arginine complex (BA-Arg) by screening for suitable basic compounds and utilizing a freeze-drying method, resulting in an amorphous solid dispersion of BA.</p><p><strong>Results: </strong>Our findings revealed that BA·Arg significantly enhances the intestinal absorption and transmembrane transport of BA without inducing toxicity in Caco-2 cells. Pharmacokinetic studies in healthy Wistar rats demonstrated significantly higher plasma concentrations of BA compared to free BA. In a mouse model induced by 3.5% dextran sodium sulfate, BA·Arg treatment markedly alleviated colitis symptoms as evidenced by reduced inflammatory cell infiltration, decreased lymphocyte aggregation in the colon, and better preservation of intestinal mucosa. This improved the overall anti-colitis efficacy of BA.</p><p><strong>Conclusions: </strong>Overall, our study presents a simple, eco-friendly formulation process that enhances BA solubility without the need for organic solvents, offering a practical and sustainable solution for developing BA-based therapies for UC.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"An Amorphous Solid Dispersion of Baicalin and its Oral Therapeutic Effect on Ulcerative Colitis.\",\"authors\":\"Yaxin Jia, Jiajia Gengji, Tao Gong, Zhirong Zhang, Li Deng\",\"doi\":\"10.1007/s11095-024-03804-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Ulcerative colitis (UC) treatment currently faces multiple challenges including adverse effects, prolonged therapy durations, and high costs. Baicalin (BA) has demonstrated anti-inflammatory benefits for inflammatory bowel disease, and the objective of this scholarly work is to address the challenges associated with the poor aqueous solubility and diminished oral bioavailability of the compound in question, thereby offering an innovative therapeutic approach for the management of ulcerative colitis.</p><p><strong>Methods: </strong>We developed a baicalin-arginine complex (BA-Arg) by screening for suitable basic compounds and utilizing a freeze-drying method, resulting in an amorphous solid dispersion of BA.</p><p><strong>Results: </strong>Our findings revealed that BA·Arg significantly enhances the intestinal absorption and transmembrane transport of BA without inducing toxicity in Caco-2 cells. Pharmacokinetic studies in healthy Wistar rats demonstrated significantly higher plasma concentrations of BA compared to free BA. In a mouse model induced by 3.5% dextran sodium sulfate, BA·Arg treatment markedly alleviated colitis symptoms as evidenced by reduced inflammatory cell infiltration, decreased lymphocyte aggregation in the colon, and better preservation of intestinal mucosa. This improved the overall anti-colitis efficacy of BA.</p><p><strong>Conclusions: </strong>Overall, our study presents a simple, eco-friendly formulation process that enhances BA solubility without the need for organic solvents, offering a practical and sustainable solution for developing BA-based therapies for UC.</p>\",\"PeriodicalId\":20027,\"journal\":{\"name\":\"Pharmaceutical Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-12-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11095-024-03804-0\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11095-024-03804-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
目的:溃疡性结肠炎(UC)的治疗目前面临多种挑战,包括不良反应、疗程长和费用高。黄芩苷(BA)已证明对炎症性肠病有抗炎作用,本学术研究的目的是解决该化合物水溶性差、口服生物利用度低等难题,从而为溃疡性结肠炎的治疗提供一种创新的治疗方法:我们通过筛选合适的碱性化合物并利用冷冻干燥法研制出了黄芩苷-精氨酸复合物(BA-Arg),从而得到了黄芩苷-精氨酸的无定形固体分散体:结果:我们的研究结果表明,BA-Arg 能明显促进肠道对 BA 的吸收和跨膜转运,且不会对 Caco-2 细胞产生毒性。在健康 Wistar 大鼠体内进行的药代动力学研究表明,与游离 BA 相比,BA 的血浆浓度明显更高。在 3.5% 右旋糖酐硫酸钠诱导的小鼠模型中,BA-Arg 治疗明显缓解了结肠炎症状,这表现在炎症细胞浸润减少、结肠淋巴细胞聚集减少以及肠粘膜保存更好。这提高了 BA 抗结肠炎的整体疗效:总之,我们的研究提出了一种简单、环保的制剂工艺,无需使用有机溶剂即可提高 BA 的溶解度,为开发基于 BA 的 UC 治疗方法提供了一种实用、可持续的解决方案。
An Amorphous Solid Dispersion of Baicalin and its Oral Therapeutic Effect on Ulcerative Colitis.
Objective: Ulcerative colitis (UC) treatment currently faces multiple challenges including adverse effects, prolonged therapy durations, and high costs. Baicalin (BA) has demonstrated anti-inflammatory benefits for inflammatory bowel disease, and the objective of this scholarly work is to address the challenges associated with the poor aqueous solubility and diminished oral bioavailability of the compound in question, thereby offering an innovative therapeutic approach for the management of ulcerative colitis.
Methods: We developed a baicalin-arginine complex (BA-Arg) by screening for suitable basic compounds and utilizing a freeze-drying method, resulting in an amorphous solid dispersion of BA.
Results: Our findings revealed that BA·Arg significantly enhances the intestinal absorption and transmembrane transport of BA without inducing toxicity in Caco-2 cells. Pharmacokinetic studies in healthy Wistar rats demonstrated significantly higher plasma concentrations of BA compared to free BA. In a mouse model induced by 3.5% dextran sodium sulfate, BA·Arg treatment markedly alleviated colitis symptoms as evidenced by reduced inflammatory cell infiltration, decreased lymphocyte aggregation in the colon, and better preservation of intestinal mucosa. This improved the overall anti-colitis efficacy of BA.
Conclusions: Overall, our study presents a simple, eco-friendly formulation process that enhances BA solubility without the need for organic solvents, offering a practical and sustainable solution for developing BA-based therapies for UC.
期刊介绍:
Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to:
-(pre)formulation engineering and processing-
computational biopharmaceutics-
drug delivery and targeting-
molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)-
pharmacokinetics, pharmacodynamics and pharmacogenetics.
Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.