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基于多糖-肠道菌群的姜黄素结肠靶向自微乳给药系统治疗多囊卵巢综合征。

Polysaccharide-fecal microbiota-based colon-targeted self-nanoemulsifying drug delivery system of curcumin for treating polycystic ovarian syndrome.

机构信息

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, Punjab, India.

Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, Australia.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Sep;397(9):6721-6743. doi: 10.1007/s00210-024-03029-3. Epub 2024 Mar 20.

Abstract

The gut microbiome is involved in the pathogenesis of many diseases including polycystic ovarian syndrome (PCOS). Modulating the gut microbiome can lead to eubiosis and treatment of various metabolic conditions. However, there is no proper study assessing the delivery of microbial technology for the treatment of such conditions. The present study involves the development of guar gum-pectin-based solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing curcumin (CCM) and fecal microbiota extract (FME) for the treatment of PCOS. The optimized S-SNEDDS containing FME and CCM was prepared by dissolving CCM (25 mg) in an isotropic mixture consisting of Labrafil M 1944 CS, Transcutol P, and Tween-80 and solidified using lactose monohydrate, aerosil-200, guar gum, and pectin (colon-targeted CCM solid self-nanoemulsifying drug delivery system [CCM-CT-S-SNEDDS]). Pharmacokinetic and pharmacodynamic evaluation was carried out on letrozole-induced female Wistar rats. The results of pharmacokinetic studies indicated about 13.11 and 23.48-fold increase in AUC of CCM-loaded colon-targeted S-SNEDDS without FME (CCM-CT-S-SNEDDS (WFME)) and CCM-loaded colon-targeted S-SNEDDS with FME [(CCM-CT-S-SNEDDS (FME)) as compared to unprocessed CCM. The pharmacodynamic study indicated excellent recovery/reversal in the rats treated with CCM-CT-S-SNEDDS low and high dose containing FME (group 13 and group 14) in a dose-dependent manner. The developed formulation showcasing its improved bioavailability, targeted action, and therapeutic activity in ameliorating PCOS can be utilized as an adjuvant therapy for developing a dosage form, scale-up, and technology transfer.

摘要

肠道微生物群参与许多疾病的发病机制,包括多囊卵巢综合征(PCOS)。调节肠道微生物群可以导致生态平衡和治疗各种代谢状况。然而,目前还没有适当的研究评估微生物技术在治疗这些疾病中的应用。本研究涉及开发基于瓜尔胶-果胶的固体自微乳化药物传递系统(S-SNEDDS),该系统包含姜黄素(CCM)和粪便微生物群提取物(FME),用于治疗 PCOS。通过将 CCM(25mg)溶解在由 Labrafil M 1944 CS、Transcutol P 和 Tween-80 组成的各向同性混合物中,并使用乳糖一水合物、aerosil-200、瓜尔胶和果胶固化,制备含有 FME 和 CCM 的优化 S-SNEDDS(CCM-CT-S-SNEDDS)。在来曲唑诱导的雌性 Wistar 大鼠上进行药代动力学和药效学评价。药代动力学研究结果表明,与未经处理的 CCM 相比,不含 FME 的载有 CCM 的结肠靶向 S-SNEDDS(CCM-CT-S-SNEDDS(WFME))和载有 CCM 的结肠靶向 S-SNEDDS 与 FME(CCM-CT-S-SNEDDS(FME))的 CCM 的 AUC 分别增加了 13.11 倍和 23.48 倍。药效学研究表明,在 FME 存在的情况下,用 CCM-CT-S-SNEDDS 低剂量和高剂量处理的大鼠(第 13 组和第 14 组)在剂量依赖性方式下,表现出极好的恢复/逆转。该制剂展示了其在改善 PCOS 方面的生物利用度、靶向作用和治疗活性的提高,可作为开发剂型、放大和技术转让的辅助治疗。

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