Development and Evaluation of a PH-Responsive Bovine Serum Albumin-Functionalized Layered Double Hydroxide Nanocarrier for Targeted Therapy of Ovarian Cancer

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmaceutical Innovation Pub Date : 2025-09-22 DOI:10.1007/s12247-025-10104-6

Mervat Shafik Ibrahim, Nihal Mohamed Elmahdy Elsayyad, Shereen H. Noshi

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引用次数: 0

Abstract

Purpose

Ovarian cancer accounts for 4.7% of cancer-related deaths in women, with paclitaxel (PAC) being an effective treatment option. However, poor water solubility and inefficient release within the tumor microenvironment limit its clinical use. This study aims to optimize a novel PAC pH-sensitive nanocarrier system based on layered double hydroxide (LDH) functionalized with bovine serum albumin (BSA) to enhance its delivery and release.

Methods

A response surface D-optimal design was utilized to optimize the formulation of BSA-d-LDH-PAC nanoparticles, considering particle size (PS), drug entrapment efficiency (EE%), and zeta potential (ZP). The optimized formulation (F3) was characterized using structural and physicochemical analyses, and in vitro drug release studies were conducted at different pH levels. Additionally, cytotoxicity studies were performed to evaluate the therapeutic potential of the developed system.

Results

The optimized formulation (F3) incorporated 16 mg/mL BSA, 0.5 mg PAC, and delaminated layered double hydroxide (d-LDH), yielding nanoparticles with a brucite-like structure, a diameter of 95 nm, a ZP of -27 mV, and an EE% of 51%. Molecular modeling and FTIR analysis confirmed the layered LDH structure and successful integration of BSA and PAC via hydrogen bonding, contributing to high drug loading and entrapment efficiency. The less ordered particle arrangement enhanced PAC aqueous solubility and facilitated rapid release, with 90% of the drug released at pH 5.5 within 5 h. Cytotoxicity studies demonstrated the superior anticancer activity of BSA-d-LDH-PAC compared to free PAC suspension.

Conclusion

BSA-functionalized LDH nanoparticles provide an efficient, pH-responsive delivery system for PAC, improving solubility, controlled release, and cytotoxic efficacy. These findings emphasize the future promise of this nanocarrier system for enhanced ovarian cancer treatment and broader applications in targeted drug delivery.

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ph响应性牛血清白蛋白功能化层状双氢氧化物纳米载体用于卵巢癌靶向治疗的研制与评价

目的卵巢癌占女性癌症相关死亡的4.7%，紫杉醇（PAC）是一种有效的治疗选择。但其水溶性差，在肿瘤微环境内释放效率低，限制了其临床应用。本研究旨在优化基于层状双氢氧化物（LDH）与牛血清白蛋白（BSA）功能化的新型PAC ph敏感纳米载体体系，以提高其递送和释放能力。方法采用响应面d优化设计，综合考虑BSA-d-LDH-PAC纳米颗粒粒径（PS）、药物包封效率（EE%）、ZP电位（ZP）等因素，优化BSA-d-LDH-PAC纳米颗粒的处方。对优化后的配方（F3）进行结构和理化表征，并在不同pH水平下进行体外释药研究。此外，还进行了细胞毒性研究，以评估开发的系统的治疗潜力。结果优化配方（F3）中添加16 mg/mL牛血清白蛋白（BSA）、0.5 mg PAC和分层双氢氧化物（d-LDH），得到的纳米颗粒具有水镁石样结构，直径为95 nm， ZP为-27 mV， EE%为51%。分子建模和FTIR分析证实了层状LDH结构，并通过氢键成功地将BSA和PAC结合在一起，从而提高了药物的负载和包载效率。不那么有序的颗粒排列增强了PAC的水溶性，促进了快速释放，90%的药物在pH 5.5下在5小时内释放。细胞毒性研究表明，与自由PAC悬浮液相比，bsa -d- ldl -PAC具有更好的抗癌活性。结论bsa功能化的LDH纳米颗粒为PAC提供了一种高效的ph响应递送系统，改善了PAC的溶解度、控释和细胞毒作用。这些发现强调了这种纳米载体系统在增强卵巢癌治疗和更广泛的靶向药物递送方面的应用前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-

CiteScore

3.70

自引率

3.80%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.