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利用脂质体纳米杂化递药系统增强伊布替尼的口服生物利用度。

Enhancement of oral bioavailability of ibrutinib using a liposil nanohybrid delivery system.

机构信息

Research Scholar, Department of Pharmacy, Annamalai University, Annamalainagar, Chidambaram, Tamil Nadu, India.

Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Kingdom of Saudi Arabia.

出版信息

PLoS One. 2024 Sep 24;19(9):e0310492. doi: 10.1371/journal.pone.0310492. eCollection 2024.

Abstract

Liposils, synthesized via the liposome templating method, offer a promising strategy for enhancing liposome stability by employing a silica coating. This study focuses on the development of nanocarriers utilizing silica-coated nanoliposomes for encapsulating the poorly water-soluble drug, ibrutinib. Ibrutinib-loaded nanoliposomes were meticulously formulated using the reverse-phase evaporation technique, serving as templates for silica coating, resulting in spherical liposils with an average size of approximately 240 nanometers. Comprehensive characterization of the liposil's physical and chemical properties was conducted using various analytical methods, including dynamic light scattering, transmission electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction analysis. Liposils demonstrated superior performance compared to ibrutinib-loaded nanoliposomes, showing sustained drug release profiles in simulated intestinal fluids and resistance to simulated gastric fluid, as confirmed by dissolution studies. Moreover, ibrutinib liposils exhibited a significant increase in half-life (4.08-fold) and notable improvement in bioavailability (3.12-fold) compared to ibrutinib suspensions, as determined by pharmacokinetic studies in rats. These findings underscore the potential of liposils as nanocarriers for orally delivering poorly water-soluble drugs, offering enhanced stability and controlled release profiles, thereby improving bioavailability prospects and therapeutic efficacy. This approach holds promise for addressing challenges associated with the oral administration of drugs with limited solubility, thereby advancing drug delivery technologies and clinical outcomes in pharmaceutical research and development.

摘要

脂质体,通过脂质体模板法合成,提供了一种通过使用二氧化硅涂层来提高脂质体稳定性的有前途的策略。本研究专注于开发利用二氧化硅涂层纳米脂质体作为载体包封疏水性差的药物伊布替尼的纳米载体。使用反相蒸发技术精心配制载有伊布替尼的纳米脂质体,作为二氧化硅涂层的模板,得到平均粒径约为 240 纳米的球形脂质体。使用各种分析方法对脂质体的物理和化学性质进行了全面表征,包括动态光散射、透射电子显微镜、傅里叶变换红外光谱和 X 射线衍射分析。脂质体的性能优于载有伊布替尼的纳米脂质体,在模拟肠液中的药物释放曲线更持久,在模拟胃液中的稳定性更高,溶解研究得到证实。此外,与伊布替尼混悬剂相比,伊布替尼脂质体的半衰期(4.08 倍)显著延长,生物利用度(3.12 倍)显著提高,通过大鼠药代动力学研究得到证实。这些发现强调了脂质体作为用于口服递送疏水性差的药物的纳米载体的潜力,提供了增强的稳定性和控制的释放曲线,从而提高生物利用度前景和治疗效果。这种方法有望解决与具有有限溶解度的药物的口服给药相关的挑战,从而推动药物输送技术和临床结果在药物研发中的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8418/11421787/ff7f08b8bdcb/pone.0310492.g001.jpg

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