Electrostatic Intraperitoneal Aerosol Delivery of Nanoparticles: Proof of Concept and Preclinical Validation.,Advanced Healthcare Materials

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Electrostatic Intraperitoneal Aerosol Delivery of Nanoparticles: Proof of Concept and Preclinical Validation.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-06-16 , DOI: 10.1002/adhm.202000655
Leen Van de Sande _{1,

2} , Mohammad Rahimi-Gorji _{1,

2,

3} , Silvia Giordano ₄ , Enrico Davoli ₄ , Cristina Matteo ₅ , Sönke Detlefsen _{6,

7} , Katharina D'Herde ₁ , Helena Braet _{2,

8} , Molood Shariati _{2,

8} , Katrien Remaut _{2,

8} , Feifan Xie ₉ , Charlotte Debbaut _{2,

3} , Ghader Ghorbaniasl ₁₀ , Sarah Cosyns _{1,

2} , Wouter Willaert _{1,

2} , Wim Ceelen _{1,

1,

2}

Affiliation

Department of Human Structure and Repair, Ghent University, Corneel Heymanslaan 10, Ghent, 9000, Belgium.
Cancer Research Institute Ghent (CRIG), Ghent University, Corneel Heymanslaan 10, Ghent, 9000, Belgium.
IBiTech - bioMMeda, Ghent University, Corneel Heymanslaan 10, Ghent, 9000, Belgium.
Mass Spectrometry Laboratory, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, Milan, 20156, Italy.
Cancer Pharmacology Laboratory, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, Milan, 20156, Italy.
Department of Pathology, Odense University Hospital, J.B. Winsløws Vej 4, Odense, 5000, Denmark.
Department of Clinical Research, University of Southern Denmark, Winsløwsparken 19, Odense, 5000, Denmark.
Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium.
Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium.
Department of Mechanical Engineering, Vrije Universiteit Brussel (VUB), Pleinlaan 2, Brussels, 1050, Belgium.

There is an increasing interest in intraperitoneal delivery of chemotherapy as an aerosol in patients with peritoneal metastasis. The currently used technology is hampered by inhomogenous drug delivery throughout the peritoneal cavity because of gravity, drag, and inertial impaction. Addition of an electrical force to aerosol particles, exerted by an electrostatic field, can improve spatial aerosol homogeneity and enhance tissue penetration. A computational fluid dynamics model shows that electrostatic precipitation (EP) results in a significantly improved aerosol distribution. Fluorescent nanoparticles (NPs) remain stable after nebulization in vitro, while EP significantly improves spatial homogeneity of NP distribution. Next, pressurized intraperitoneal chemotherapy with and without EP using NP albumin bound paclitaxel (Nab‐PTX) in a novel rat model is examined. EP does not worsen the effects of CO₂ insufflation and intraperitoneal Nab‐PTX on mesothelial structural integrity or the severity of peritoneal inflammation. Importantly, EP significantly enhances tissue penetration of Nab‐PTX in the anatomical regions not facing the nozzle of the nebulizer. Also, the addition of EP leads to more homogenous peritoneal tissue concentrations of Nab‐PTX, in parallel with higher plasma concentrations. In conclusion, EP enhances spatial homogeneity and tissue uptake after intraperitoneal nebulization of anticancer NPs.

中文翻译：

纳米粒子的静电腹膜内气雾剂递送：概念验证和临床前验证。

在腹膜转移患者中，腹膜内以气雾剂形式进行化学治疗的兴趣日益增加。由于重力，阻力和惯性冲击，整个腹膜腔内的药物输送不均匀阻碍了当前使用的技术。由静电场施加的力施加到气溶胶颗粒上，可以改善空间气溶胶的均匀性并增强组织穿透力。计算的流体动力学模型表明，静电沉淀（EP）可以显着改善气溶胶分布。在体外雾化后，荧光纳米颗粒（NPs）保持稳定，而EP则显着提高了NP分布的空间均匀性。下一个，在新型大鼠模型中，使用NP白蛋白结合的紫杉醇（Nab-PTX）对有或没有EP的加压腹膜内化疗进行了检查。EP不会恶化CO的作用₂吹气和腹膜内Nab-PTX对间皮结构完整性或腹膜炎症的严重性。重要的是，EP显着增强了Nab-PTX在不面向雾化器喷嘴的解剖区域的组织穿透力。同样，添加EP会导致Nab-PTX的腹膜组织浓度更高，同时血浆浓度更高。总之，EP可增强腹膜内雾化抗癌NP后的空间均匀性和组织摄取。

更新日期：2020-08-19

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