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层状醋酸纤维素包裹的载紫杉醇聚(乳酸-共-乙醇酸)酸纳米粒的工程化用于前列腺癌治疗的体外研究。

Engineering of layer-by-layer acetate-coated paclitaxel loaded poly(lactide-co-glycolide) acid nanoparticles for prostate cancer therapy- in vitro.

机构信息

Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Division of Pharmaceutical Sciences, Tallahassee, FL 32307, United States.

Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Division of Pharmaceutical Sciences, Tallahassee, FL 32307, United States.

出版信息

J Pharm Sci. 2024 Nov;113(11):3375-3383. doi: 10.1016/j.xphs.2024.09.014. Epub 2024 Sep 21.

Abstract

It is hypothesized that layer-by-layer acetate-coated Paclitaxel-loaded PLGA nanoparticles (F2) can be engineered to potentiate the effectiveness of Paclitaxel (PTX) on LNCaP, a human prostate cancer cell line. The core of the layer-by-layer NPs is formed by nanoprecipitation, and the shell of the NPs is engineered using the sodium acetate's unique coating mechanism and surface-active properties. The resulting nanoformulation physicochemical properties are characterized by Fourier Transform Infra-Red (FTIR), Differential Scanning Calorimetry (DSC) Transmission Electron Microscopy (TEM), NanoSight NS300, spectrophotometry, Korsmeyer-Peppas model, respectively. The NP's cytotoxicity on LNCaP is assessed by MTS assay. The DSC and the FTIR confirm SA's coating of the NPs. The particle's mean diameters (PMD) are 89.4±2.3- to 114.4±7.6 nm. The TEM shows a unique multilayer and spherical nanoparticle. The encapsulation efficiency of commonly PTX-loaded PLGA NPs (F1) and F2 are 84.37±2.71% and 86.74±2.22, respectively. The drug transport mechanism of F1 and F2 is anomalous transport and case II, respectively. F2 follows a zero-order release mechanism. The cell viability is 45.08±2.18% and 60.17±4.72% when LNCaP is treated with 10 µg/mL of F2 and F1, respectively, after 48 hours of exposure. F2 and F1 cell growth inhibition are dose-dependent. This unique process of engineering the layer-by-layer NPs will provide new horizons for developing future innovative nanoparticles for targeted prostate cancer therapy.

摘要

据推测,通过层层包裹醋酸纤维素的载紫杉醇 PLGA 纳米粒(F2)可以增强紫杉醇(PTX)对人前列腺癌细胞系 LNCaP 的疗效。层层纳米粒的核心是通过纳米沉淀形成的,纳米粒的外壳是利用醋酸钠独特的涂层机制和表面活性特性设计的。所得纳米制剂的物理化学性质分别通过傅里叶变换红外(FTIR)、差示扫描量热法(DSC)、透射电子显微镜(TEM)、纳米视(NanoSight NS300)、分光光度法、Korsmeyer-Peppas 模型进行了表征。通过 MTS 测定评估 NP 对 LNCaP 的细胞毒性。DSC 和 FTIR 证实了 SA 对 NP 的涂层。颗粒的平均粒径(PMD)为 89.4±2.3-114.4±7.6nm。TEM 显示出独特的多层和球形纳米颗粒。通常载有紫杉醇的 PLGA NPs(F1)和 F2 的包封效率分别为 84.37±2.71%和 86.74±2.22%。F1 和 F2 的药物转运机制分别为异常转运和 II 型。F2 遵循零级释放机制。LNCaP 暴露 48 小时后,用 10μg/mL 的 F2 和 F1 处理,细胞活力分别为 45.08±2.18%和 60.17±4.72%。F2 和 F1 的细胞生长抑制呈剂量依赖性。这种独特的层层纳米粒工程化过程将为开发用于靶向前列腺癌治疗的未来创新纳米粒提供新的视野。

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