Preparation and <i>in vitro</i> characterization of remdesivir-loaded liposomes for inhalation

ZHAO Di; LI Jingjing; ZHANG Kai; QIN Chao; YANG Lei; YIN Lifang

doi:10.11665/j.issn.1000-5048.20210506

Journal of China Pharmaceutical University > 2021 > 52(5): 547-554. > DOI: 10.11665/j.issn.1000-5048.20210506

ZHAO Di, LI Jingjing, ZHANG Kai, QIN Chao, YANG Lei, YIN Lifang. Preparation and in vitro characterization of remdesivir-loaded liposomes for inhalation[J]. Journal of China Pharmaceutical University, 2021, 52(5): 547-554. DOI: 10.11665/j.issn.1000-5048.20210506

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Preparation and in vitro characterization of remdesivir-loaded liposomes for inhalation

Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China

Funds: This study was supported by the National Natural Science Foundation of China (No.81871477, No.81673377); China National Key Hi-Tech Innovation Project for the R&D of Novel Drugs (No.2017ZX09101001-004) and the Emergency Research Project for COVID-19 of China Pharmaceutical University (No.2632020ZX007)

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Received Date: February 17, 2021
Revised Date: May 09, 2021

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Abstract

Abstract

Remdesivir-loaded liposomes for inhalation were prepared and the in vitro properties were evaluated. Firstly, preparation methods of remdesivir-loaded liposomes were screened, and single-factor experiments were conducted to optimize the prescription and preparation process. Then the physical property, deposition ratio and aerodynamic particle size distribution of remdesivir-loaded liposomes suspension for inhalation were comprehensively evaluated. As a result, the optimal liposomes were prepared by the thin-film dispersion method with pH 6.5 phosphate-buffered saline as the hydration medium. In the prescription, the ratio of drug to DPPC was 1∶20; the cholesterol accounted for 10% of total lipids; and 20% DSPE-mPEG 2000 was added as stabilizer.4% trehalose was added as lyoprotectant when lyophilizing to obtain ideal appearance, good stability and a small particle size change after reconstitution. Remdesivir-loaded liposomes were spherical with smooth surface and uniform particle size distribution under transmission electron microscope. In vitro release tests showed no significant change for release curves of remdesivir-loaded liposomes suspension before and after nebulization. Deposition experiments indicated that the fine particles fraction of liposomes was 51.4%, and the mass median aerodynamic diameter was less than 5 μm measured by next generation impactor. To sum up, remdesivir-loaded liposomes for inhalation with high encapsulation efficiency and stability can achieve a suitable particle size distribution to effectively deposit in the lung after nebulization, which provides a new approach for the treatment of COVID-19.
- remdesivir,
- liposomes,
- inhalation,
- preparation,
- aerodynamics

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References

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