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...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.展开更多
In the present study,we analyzed the structures of the two unknown impurities that were contained more than 0.1% in triamcinolone acetonide palmitate by using HPLC-DAD and HPLC-MS hyphenated techniques,and these impur...In the present study,we analyzed the structures of the two unknown impurities that were contained more than 0.1% in triamcinolone acetonide palmitate by using HPLC-DAD and HPLC-MS hyphenated techniques,and these impurities were synthesized and purified by column chromatography.Based on the results of NMR spectroscopy,IR spectroscopy,and MS,the two impurities were confirmed as 9-fluoro-11β,21-dihydroxy-16α,17-(isopropylidenedioxy)pregna-1,4-diene-3,20-dione 21-myristate and stearate,respectively.展开更多
基金supported by National Natural Science Foundation(81871477,81603051,and 81673377)Natural Science Foundation of Jiangsu Province(BK20160760 and BK20170748)+2 种基金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).
文摘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.
文摘In the present study,we analyzed the structures of the two unknown impurities that were contained more than 0.1% in triamcinolone acetonide palmitate by using HPLC-DAD and HPLC-MS hyphenated techniques,and these impurities were synthesized and purified by column chromatography.Based on the results of NMR spectroscopy,IR spectroscopy,and MS,the two impurities were confirmed as 9-fluoro-11β,21-dihydroxy-16α,17-(isopropylidenedioxy)pregna-1,4-diene-3,20-dione 21-myristate and stearate,respectively.
