Liposomal remdesivir inhalation solution for targeted lung delivery as a novel therapeutic approach for COVID-19  

作　　者：Jingjing Li Kai Zhang Di Wua Lianjie Ren Xinyu Chu Chao Qin Xiaopeng Han Taijun Hang Yungen Xu Lei Yang Lifang Yina 

机构地区：[1]Jiangsu Province Engineering Research Center for R&D and Evaluation of Intelligent Drugs and Key Functional Excipients,China Pharmaceutical University,Nanjing 210009,China [2]Department of Pharmaceutical Analysis,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China [3]Department of Medicinal Chemistry,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2021年第6期772-783,共12页亚洲药物制剂科学（英文）

基　　金：supported by National Natural Science Foundation(81871477,81603051,and 81673377);Natural Science Foundation of Jiangsu Province(BK20160760 and BK20170748);The Anti-COVID-19 Emergency Research Project of China Pharmaceutical University(2632020ZX007);The Creation of Major New Drugs National Major Projects(2017ZX09101001-004);Fundamental Research Funds for the Central Universities(2016ZPY015,2632017PY18).

摘　　要：Strong infectivity enables coronavirus disease 2019(COVID-19)to rage throughout the world.Moreover,the lack of drugs with definite therapeutic effects further aggravates the spread of the pandemic.Remdesivir is one of the most promising anti-severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)drugs.However,the limited clinical effects make its therapeutic effect controversial,which may result from the poor accumulation and activation of remdesivir in the lung.Therefore,we developed lyophilized remdesivir liposomes(Rdv-lips)which can be reconstituted as liposomal aerosol for pulmonary delivery to improve the in vivo behavior of existing remdesivir cyclodextrin conclusion compound(Rdv-cyc)injections.Liposome encapsulation endowed remdesivir with much higher solubility and better biocompatibility.The in vitro liposomal aerosol characterization demonstrated that Rdv-lips possessed a mass median aerodynamic diameter of 4.118μm and fine particle fraction(<5μm)higher than 50%,indicating good pulmonary delivery properties.Compared to the Rdv-cyc intravenous injection group,the Rdv-lips inhalation group displayed a nearly 100-fold increase in the remdesivir-active metabolite nucleotide triphosphate(NTP)concentration and better NTP accumulation in the lung than the Rdv-cyc inhalation group.A faster transition from remdesivir to NTP of Rdv-lips(inhalation)could also be observed due to better cell uptake.Compared to other preparations,the superiority of Rdv-lips was further evidenced by the results of an in vivo safety study,with little possibility of inducing inflammation.In conclusion,Rdv-lips for pulmonary delivery will be a potent formulation to improve the in vivo behavior of remdesivir and exert better therapeutic effects in COVID-19 treatment.

关 键 词：COVID-19 Remdesivir Pulmonary delivery Liposomal aerosol Nucleotide triphosphate 

分 类 号：R563.1[医药卫生—呼吸系统]