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基于聚乳酸-羟基乙酸共聚物的吉西他滨纳米胶囊的设计与优化以增强胰腺癌疗效

Design and optimization of PLGA-based gemcitabine nanocapsule for enhanced pancreatic cancer efficacy.

作者信息

Tiwari Gaurav, Panda Satyajit, Diyya A Salomy Monica, Thomas Noel Vinay, Deka Trinayan, Rudrangi Shashi Ravi Suman, Patel Gaurav, Sharma Pankaj

机构信息

PSIT-Pranveer Singh Institute of Technology (Pharmacy), Kanpur-Agra-Delhi National, NH 19, Kanpur, Uttar Pradesh, 209305, India.

Department of Pharmaceutics, Institute of Pharmacy and Technology, Salipur, Cuttack, Odisha, 754202, India.

出版信息

Invest New Drugs. 2025 Jul 23. doi: 10.1007/s10637-025-01567-y.

DOI:10.1007/s10637-025-01567-y
PMID:40696247
Abstract

This study aimed to develop gemcitabine-loaded nanocapsules for pancreatic cancer treatment, optimizing their formulation before evaluating them through in vivo studies. The researchers selected gemcitabine as the model drug because it has established clinical relevance and known pharmacokinetic shortfalls (short half-life and poor bioavailability) with toxic dose limits which suit the evaluation of nanoparticle drug delivery systems. The researchers conducted a 3 factorial design to optimize the formulation through adjustments of PLGA concentration and Tween 80 concentration. The optimal characteristics of F5 among nine formulations included particles of 160 ± 3 nm with 87 ± 2% encapsulation efficiency and - 27.8 ± 1.2 mV zeta potential. The in vitro drug release testing alongside pharmacokinetic results established that nanoparticle gemcitabine caused extended drug delivery and dramatically better bioavailability in addition to achieving longer systemic circulation than free gemcitabine alone. Evaluation of biodistribution revealed that the product displayed tumor-targeting property and had improved antitumor effect and less side effect compared with the other groups. The findings demonstrate that gemcitabine works as an ideal model chemotherapy drug to measure nanocarrier delivery platforms for treating pancreatic cancer solid tumors.

摘要

本研究旨在开发用于胰腺癌治疗的载吉西他滨纳米胶囊,在通过体内研究对其进行评估之前优化其配方。研究人员选择吉西他滨作为模型药物,因为它具有已确立的临床相关性以及已知的药代动力学缺陷(半衰期短和生物利用度差),其毒性剂量限制适合评估纳米颗粒药物递送系统。研究人员进行了三因素设计,通过调整聚乳酸-羟基乙酸共聚物(PLGA)浓度和吐温80浓度来优化配方。九种配方中F5的最佳特性包括粒径为160±3纳米、包封率为87±2%以及ζ电位为-27.8±1.2毫伏。体外药物释放测试以及药代动力学结果表明,纳米颗粒吉西他滨除了比游离吉西他滨单独使用具有更长的全身循环时间外,还能实现延长的药物递送并显著提高生物利用度。生物分布评估显示,与其他组相比,该产品具有肿瘤靶向特性,抗肿瘤效果更好且副作用更小。研究结果表明,吉西他滨是一种理想的模型化疗药物,可用于衡量治疗胰腺癌实体瘤的纳米载体递送平台。

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本文引用的文献

1
Drug Combination Nanoparticles Containing Gemcitabine and Paclitaxel Enable Orthotopic 4T1 Breast Tumor Regression.含吉西他滨和紫杉醇的药物组合纳米颗粒可使原位4T1乳腺肿瘤消退。
Cancers (Basel). 2024 Aug 8;16(16):2792. doi: 10.3390/cancers16162792.
2
A Systematic Investigation of the Kinetic Models Applied to the Transport Behaviors of Aromatic Solvents in Unfilled Hydrogenated Nitrile Rubber/Ethylene Propylene Diene Monomer Composites.应用于未填充氢化丁腈橡胶/三元乙丙橡胶复合材料中芳烃溶剂传输行为的动力学模型的系统研究。
Polymers (Basel). 2024 Mar 25;16(7):892. doi: 10.3390/polym16070892.
3
Meta-Analysis of Nanoparticle Distribution in Tumors and Major Organs in Tumor-Bearing Mice.
肿瘤荷瘤小鼠中肿瘤和主要器官内纳米颗粒分布的荟萃分析。
ACS Nano. 2023 Oct 24;17(20):19810-19831. doi: 10.1021/acsnano.3c04037. Epub 2023 Oct 9.
4
Lipid polymer hybrid nanoparticles: a custom-tailored next-generation approach for cancer therapeutics.脂质聚合物杂化纳米粒:一种为癌症治疗定制的新一代方法。
Mol Cancer. 2023 Oct 3;22(1):160. doi: 10.1186/s12943-023-01849-0.
5
Nanomedicine in cancer therapy.癌症治疗中的纳米医学。
Signal Transduct Target Ther. 2023 Aug 7;8(1):293. doi: 10.1038/s41392-023-01536-y.
6
Advances in Lung Cancer Treatment Using Nanomedicines.肺癌纳米药物治疗进展
ACS Omega. 2022 Dec 29;8(1):10-41. doi: 10.1021/acsomega.2c04078. eCollection 2023 Jan 10.
7
Drug Stability: ICH versus Accelerated Predictive Stability Studies.药物稳定性:国际协调会议(ICH)与加速预测稳定性研究
Pharmaceutics. 2022 Oct 28;14(11):2324. doi: 10.3390/pharmaceutics14112324.
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World J Gastroenterol. 2022 Aug 28;28(32):4698-4715. doi: 10.3748/wjg.v28.i32.4698.
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