김정환 (Oregon State University, 영남대학교 약학대학) | 한빛사논문 > 한빛사

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조회541

김정환Jeonghwan Kim

Oregon State University, 영남대학교 약학대학

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ACS Nano, Apr 15 2024, | https://doi.org/10.1021/acsnano.4c00768 Microfluidic Platform Enables Shearless Aerosolization of Lipid Nanoparticles for mRNA Inhalation

Jeonghwan Kim ^1,2, Antony Jozić ¹, Elissa Bloom¹, Brian Jones ³, Michael Marra ³, Namratha Turuvekere Vittala Murthy ¹, Yulia Eygeris ¹, Gaurav Sahay ^1,4,5,6

¹Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, Oregon 97201, United States.

²College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.

³Funai Microfluidic Systems, Lexington, Kentucky 40508, United States.

⁴Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon 97201, United States.

⁵Department of Biomedical Engineering, Robertson Life Sciences Building, Oregon Health & Science University, Portland, Oregon 97201, United States.

⁶Center for Innovative Drug Delivery and Imaging, College of Pharmacy, Oregon State University, Portland, Oregon 97201, United States.

J.K. and A.J. contributed equally to this work.

Corresponding Author : Gaurav Sahay

Abstract

Leveraging the extensive surface area of the lungs for gene therapy, the inhalation route offers distinct advantages for delivery. Clinical nebulizers that employ vibrating mesh technology are the standard choice for converting liquid medicines into aerosols. However, they have limitations when it comes to delivering mRNA through inhalation, including severe damage to nanoparticles due to shearing forces. Here, we introduce a microfluidic aerosolization platform (MAP) that preserves the structural and physicochemical integrity of lipid nanoparticles, enabling safe and efficient delivery of mRNA to the respiratory system. Our results demonstrated the superiority of the MAP over the conventional vibrating mesh nebulizer, as it avoided problems such as particle aggregation, loss of mRNA encapsulation, and deformation of the nanoparticle morphology. Notably, aerosolized nanoparticles generated by the microfluidic device led to enhanced transfection efficiency across various cell lines. In vivo experiments with mice that inhaled these aerosolized nanoparticles revealed successful lung-specific mRNA transfection without observable signs of toxicity. This MAP may represent an advancement for the pulmonary gene therapy, enabling precise and effective delivery of aerosolized nanoparticles.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-04-16)
연구진국내+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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