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自乳化药物传递系统用于口服抗癌治疗:限制因素和最新进展。

Self-emulsifying Drug Delivery System for Oral Anticancer Therapy: Constraints and Recent Development.

机构信息

Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, Vile Parle West, Mumbai 400056, India.

出版信息

Curr Pharm Des. 2022;28(31):2538-2553. doi: 10.2174/03666220606143443.

Abstract

Oral anticancer therapy faces several drawbacks: low aqueous solubility, poor and irregular absorption from gastrointestinal sites, high first-pass metabolism, food-influenced absorption, non-targeted delivery, severe systemic and local adverse effects, etc. Enhancement of oral bioavailability could reduce the drug load and associated adverse effects. Self-emulsifying drug delivery systems (SEDDS) can enhance in-vivo solubility and drug absorption from the gastrointestinal tract, bypass liver metabolism by lymphatic absorption and inhibit efflux transport. All these phenomena ultimately result in improved oral bioavailability. Anticancer drug delivery using the SEDDS has shown promising results for bioavailability and pharmacodynamic response. A handful of research studies have produced evidence of the successful loading of anticancer agents in SEDDS-based formulations. Various potent and established chemotherapeutic agents such as docetaxel, paclitaxel, etoposide, 5 Fluorouracil, doxorubicin etc., have been successfully formulated and evaluated. Improved bioavailability and reduction of dose might be possible by SEDDS. It could be effective for low-dose drugs. But, excessive surfactant- cosurfactant concentration, lacking predictive in-vitro models and adequate IVIVC, and unavailability of toxicity data are certain challenges for future researchers. No clinical trials have been recorded with anticancer drug-loaded SEDDS. Overcoming the challenges and further progression to clinical studies are required to avail the benefits of anticancer SEDDS.

摘要

口服抗癌疗法面临一些缺点

水溶解度低、从胃肠道部位吸收不良且不规则、首过代谢高、受食物影响的吸收、非靶向递送、严重的全身和局部不良反应等。提高口服生物利用度可以降低药物负荷和相关的不良反应。自乳化药物递送系统(SEDDS)可以提高体内胃肠道的溶解度和药物吸收,通过淋巴吸收绕过肝脏代谢并抑制外排转运。所有这些现象最终都导致了口服生物利用度的提高。使用 SEDDS 的抗癌药物递送在生物利用度和药效反应方面显示出了有希望的结果。少数研究已经证明了成功地将抗癌药物载入 SEDDS 制剂中。各种有效的和已建立的化疗药物,如多西紫杉醇、紫杉醇、依托泊苷、5-氟尿嘧啶、阿霉素等,已经被成功地配制和评估。SEDDS 可能会提高生物利用度并减少剂量。它可能对低剂量药物有效。但是,表面活性剂-共溶剂浓度过高、缺乏预测性的体外模型和适当的 IVIVC 以及缺乏毒性数据是未来研究人员的一些挑战。没有记录到载有抗癌药物的 SEDDS 的临床试验。需要克服这些挑战并进一步推进到临床研究,以利用抗癌 SEDDS 的优势。

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