静电沉淀法增强气雾剂腹腔给药的建模和体外评价

IF 4.7 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Mohammad Rahimi-Gorji , Yiwen Long , Amrit Sareen , Charlotte Debbaut , Ghader Ghorbaniasl , Wouter Willaert , Wim Ceelen
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引用次数: 0

摘要

腹膜转移瘤(PM)由于对全身化疗的抵抗,仍然是一个重大的临床挑战。腹腔雾化给药(IPADD)已显示出作为局部治疗选择的希望;然而,其功效往往受到气溶胶液滴分布不足和组织穿透性差的限制。在这项研究中,我们使用静电沉淀(eIPADD)来增强IPADD,并通过计算模拟和体外/离体实验来评估其性能。采用真实的人体腹腔三维重建模型,模拟静电场对液滴分布和沉积的影响。结果表明,多个电极改善了气溶胶均匀性和组织穿透深度。这些发现在体外得到了验证,eIPADD显著增加了液滴覆盖和组织渗透,特别是在解剖学上具有挑战性的区域。重要的是,将电极数量从一个增加到三个,进一步提高了液滴分布的均匀性和组织渗透深度。虽然提高电势可以改善关键区域的沉积,但在10 kV以上的效果趋于稳定,表明有效性存在阈值。然而,在这个范围内优化电压,结合增加电极数量,对于实现药物在腹膜表面的一致递送和最大化治疗效果仍然至关重要。我们的研究结果表明,eIPADD有潜力解决传统IPADD的局限性,为治疗PM提供更有效和统一的给药方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Modeling and ex vivo evaluation of electrostatic precipitation-enhanced intraperitoneal aerosol drug delivery

Modeling and ex vivo evaluation of electrostatic precipitation-enhanced intraperitoneal aerosol drug delivery
Peritoneal metastases (PM) remain a significant clinical challenge due to their resistance to systemic chemotherapy. Intraperitoneal aerosolized drug delivery (IPADD) has shown promise as a localized treatment option; however, its efficacy is often limited by inadequate aerosol droplet distribution and poor tissue penetration. In this study, we enhance IPADD using electrostatic precipitation (eIPADD) and evaluate its performance through computational simulations and in vitro/ex vivo experiments. A realistic 3D reconstruction of the human peritoneal cavity was used to simulate the effects of electrostatic fields on droplet distribution and deposition. The results demonstrated that multiple electrodes improved aerosol homogeneity and tissue penetration depth. These findings were validated in vitro, where eIPADD significantly increased droplet coverage and tissue penetration, particularly in anatomically challenging regions. Importantly, increasing the number of electrodes from one to three further enhanced droplet distribution uniformity and tissue penetration depth. While raising the electrical potential improved deposition in key areas, benefits plateaued beyond 10 kV, suggesting a threshold in efficacy. Nevertheless, optimizing voltage within this range, in conjunction with the increased electrode count, remains critical for achieving consistent drug delivery across the peritoneal surfaces and maximizing therapeutic outcomes. Our findings suggest that eIPADD has the potential to address the limitations of conventional IPADD, providing a more effective and uniform drug delivery method for treating PM.
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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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