Quality by design empowered preparation of itraconazole albumin nanoparticles for prostate cancer.

IF 5.7 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Drug Delivery and Translational Research Pub Date : 2025-01-01 Epub Date: 2024-05-02 DOI:10.1007/s13346-024-01592-z

Saurabh Shah, Paras Famta, Anamika Sharma, Rahul Kumar, Giriraj Pandey, Ganesh Vambhurkar, Dadi A Srinivasarao, Akshay Shinde, Sajja Bhanu Prasad, Amit Asthana, Saurabh Srivastava

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Abstract

The current advent explores the potential of itraconazole (ITR) in prostate cancer (PCa), by its incorporation into albumin nanoparticles (NP). ITR as a repurposed moiety has displayed tremendous potential in various cancers. However, poor aqueous solubility poses hurdles towards its clinical translation. Amorphisation of ITR was observed post-incorporation within NP matrix which could prevent its precipitation in aqueous media. ITR NP was developed using quality by design and multivariate analysis and evaluated for cellular uptake, cell proliferation inhibition and the mechanism of PCa cell inhibition. Time and concentration-dependent serum stability and hemolytic potential revealed safety of ITR NP. Morphological changes and nuclear staining studies revealed the efficacy of ITR and ITR NP in promoting growth inhibition of PC-3 cells. Superior qualitative and quantitative uptake, reactive oxygen species (ROS) and mitochondrial impairment for ITR NP in comparison with ITR and control group was observed. Cell cycle study revealed remarkable G2/M phase inhibition in PC-3 cells. ITR NP demonstrated superior anticancer potential in 3D tumoroids mimicking the micro-metastatic lesions compared to control and ITR. Hence, ITR NP can be a favorable alternative therapeutic alternative in PCa.

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通过设计提高伊曲康唑白蛋白纳米粒子的制备质量，用于治疗前列腺癌。

目前的研究探索了伊曲康唑（ITR）通过加入白蛋白纳米颗粒（NP）治疗前列腺癌（PCa）的潜力。ITR 作为一种重新利用的分子，在各种癌症中显示出巨大的潜力。然而，较差的水溶性为其临床转化带来了障碍。在 NP 基质中加入 ITR 后，观察到其发生了非晶化，这可能会阻止其在水介质中沉淀。采用质量设计和多元分析方法开发了 ITR NP，并对其细胞吸收、细胞增殖抑制和 PCa 细胞抑制机制进行了评估。与时间和浓度相关的血清稳定性和溶血潜能显示了 ITR NP 的安全性。形态学变化和核染色研究显示了 ITR 和 ITR NP 在促进 PC-3 细胞生长抑制方面的功效。与 ITR 组和对照组相比，ITR NP 的定性和定量吸收、活性氧（ROS）和线粒体损伤均优于对照组。细胞周期研究显示，PC-3 细胞的 G2/M 期抑制作用明显。与对照组和 ITR 组相比，ITR NP 在模拟微转移病灶的三维肿瘤组织中表现出更高的抗癌潜力。因此，ITR NP 可以成为治疗 PCa 的有利替代疗法。

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来源期刊

Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY

CiteScore

11.70

自引率

1.90%

发文量

160

期刊介绍： The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.