Development of Sesamol Loaded-Polymer-Lipid Blend Nanoparticles: Statistical Optimization, In-Vitro, and Preclinical Assessment

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmaceutical Innovation Pub Date : 2025-06-23 DOI:10.1007/s12247-025-10016-5

Ameeduzzafar Zafar, Mohd Yasir, Md Ali Mujtaba, Mohammad Khalid, Dibya Sundar Panda, Lubhan Singh, Omar Awad Alsaidan, Anwarulabedin Mohsin Quazi

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引用次数: 0

Abstract

Background

The oral route is the most preferred drug delivery method for treating both chronic and acute diseases due to its ease of administration and high patient compliance. However, sesamol (SM), a natural bioactive compound, exhibits promising antioxidant and anticancer activity but suffers from poor water solubility, inconsistent absorption, and low bioavailability, limiting its therapeutic potential. This study aimed to develop SM-loaded hybrid nanoparticles (HNP) composed of a polymer-lipid matrix to enhance bioavailability and therapeutic efficacy for its antioxidant potential and anticancer activity.

Method

SMHNP were formulated using homogenization and ionotropic gelation techniques and optimized by Box-Behnken design using design expert software. The SMHNP were evaluated through in-vitro and in vivo studies using the albino Wistar rat model.

Results

The optimized SMHNP formulation (SMHNP13) exhibits a particle size of 177.6 ± 4.7 nm, a polydispersity index of 0.179, and a zeta potential of 27.2 mV. Scanning electron microscopy (SEM) confirmed that the particles were spherical and non-aggregated. FTIR and X-ray diffraction (XRD) analyses indicated successful drug encapsulation within the HNP matrix. The SMHNP13 formulation exhibited a sustained drug release profile, with 92.81 ± 3.76% release over 24 h, attributed to its nanosize and encapsulation. It displayed 2.45-fold higher ex-vivo intestinal permeation and significantly higher in-vitro antioxidant activity (P < 0.05) at all tested concentrations than pure SM. It also increased cytotoxicity against SK-LU-1 cells (IC50 = 590.23 µM) compared to pure SM (IC50 = 1510.12 µM) and demonstrated a 3.33-fold higher relative bioavailability than pure SM.

Conclusion

The results indicate that HNP are a promising strategy for enhancing the oral bioavailability and therapeutic potential of sesamol. Further preclinical investigations are needed to confirm their clinical applicability.

Graphical Abstract

Abstract Image

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芝麻酚负载聚合物-脂质混合纳米颗粒的开发：统计优化，体外和临床前评估

背景：口服给药容易，患者依从性高，是治疗慢性和急性疾病的首选给药方法。然而，芝麻醇（SM）作为一种天然生物活性化合物，具有良好的抗氧化和抗癌活性，但其水溶性差，吸收不一致，生物利用度低，限制了其治疗潜力。本研究旨在开发由聚合物-脂质基质组成的sm -负载混合纳米粒子（HNP），以提高其抗氧化和抗癌活性的生物利用度和治疗效果。方法采用均质化和离子化凝胶法制备smhnp，采用Box-Behnken设计优化。采用白化Wistar大鼠模型，通过体外和体内研究评估SMHNP。结果优化后的SMHNP配方（SMHNP13）粒径为177.6±4.7 nm，多分散性指数为0.179，zeta电位为27.2 mV。扫描电镜（SEM）证实，颗粒呈球形，未聚集。红外光谱（FTIR）和x射线衍射（XRD）分析表明药物在HNP基质内包封成功。SMHNP13具有较好的缓释特性，24 h内释药率为92.81±3.76%。在所有测试浓度下，其离体肠道渗透率均比纯SM高2.45倍，体外抗氧化活性显著高于纯SM （P < 0.05）。与纯SM （IC50 = 1510.12µM）相比，它还增加了SK-LU-1细胞的细胞毒性（IC50 = 590.23µM），并显示出比纯SM高3.33倍的相对生物利用度。结论HNP是提高芝麻酚口服生物利用度和治疗潜力的有效方法。需要进一步的临床前研究来证实其临床适用性。图形抽象

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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.