{"title":"甲磺酸卡莫他雾化治疗SARS-CoV- 2感染的配方及体外试验","authors":"Rama Kashikar, Arun Kumar Kotha, Rakshya Shrestha, Rudragouda Channappanavar, Mahavir Bhupal Chougule","doi":"10.1208/s12249-025-03099-3","DOIUrl":null,"url":null,"abstract":"<div><p>COVID- 19, caused by the coronavirus SARS-CoV- 2, has arisen as a global health epidemic, claiming the lives of millions of people throughout the world. Combating the pandemic has involved developing and approving vaccines and antiviral products. Camostat Mesylate (Camo) is a TMPRSS2 inhibitor that inhibits virus-cell membrane fusion and, thereby, viral multiplication. Significant limitations of using oral Camo include the limited amount of Camo reaching the site of action, lungs, side effects due to distribution to all tissues, and enzymatic breakdown in the gut. This investigation aims to develop self-administrable and patient-compliant extended-release Camo-loaded pegylated nanoliposomes (Camo-pegNLs) for delivering Camo directly to the lungs, thereby enabling faster onset of action and overcoming limitations of oral Camo delivery. We developed the Camo-pegNLs were composed of 1,2-dipalmitoyl-sn-glycerol- 3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycerol- 3-phosphoethanolamine (DOPE-PEG, MW2000) and cholesterol using the ethanol injection technique and syringe pump. The NLs were characterized for their particle size, polydispersity index (PDI), and zeta potential using Malvern Zetasizer. The assay, unentrapped Camo using Vivaspin 500 ultrafilter (10 kDa) and in-vitro release were determined. The Camo content was analyzed using a validated HPLC method. The aerodynamic properties of Camo-pegNLs were determined using a Westech Andersen Cascade Impactor (ACI) at 28.3L/min and a pneumatic jet nebulizer. The antiviral effect of Camo-pegNLs was assessed in Vero cells expressing TMPRSS2 and infected with SARS-CoV- 2. Camo-pegNLs suspension showed size of 167.50 ± 0.90 nm, zeta potential of 0.48 ± 0.04 mV, and PDI of 0.07 ± 0.01. The quantity of entrapped Camo was found to be 44.86 ± 1.35%w/v, and the drug loading was 27.41 ± 0.04%w/w. The Camo-pegNL- 2 had an extended release of up to 24 h, MMAD of 4.295 ± 0.1 µm, GSD of 1.915 ± 0.064, and FPF of 42.01% ± 6.90. Camo-pegNLs showed a significant antiviral effect on Vero cells compared to no treatment group (<i>p</i> < 0.01). An efficacious nebulized Camo-pegNLs suspension product was successfully developed for direct lung delivery to Camo-pegNLs to treat the SARS-CoV- 2 infection.</p><h3>Graphical Abstract</h3><p>SARS-CoV- 2</p>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03099-3.pdf","citationCount":"0","resultStr":"{\"title\":\"Formulation and In-Vitro Testing of Nebulized Camostat Mesylate Loaded Nanoliposomes for the Treatment of SARS-CoV- 2 Infection\",\"authors\":\"Rama Kashikar, Arun Kumar Kotha, Rakshya Shrestha, Rudragouda Channappanavar, Mahavir Bhupal Chougule\",\"doi\":\"10.1208/s12249-025-03099-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>COVID- 19, caused by the coronavirus SARS-CoV- 2, has arisen as a global health epidemic, claiming the lives of millions of people throughout the world. Combating the pandemic has involved developing and approving vaccines and antiviral products. Camostat Mesylate (Camo) is a TMPRSS2 inhibitor that inhibits virus-cell membrane fusion and, thereby, viral multiplication. Significant limitations of using oral Camo include the limited amount of Camo reaching the site of action, lungs, side effects due to distribution to all tissues, and enzymatic breakdown in the gut. This investigation aims to develop self-administrable and patient-compliant extended-release Camo-loaded pegylated nanoliposomes (Camo-pegNLs) for delivering Camo directly to the lungs, thereby enabling faster onset of action and overcoming limitations of oral Camo delivery. We developed the Camo-pegNLs were composed of 1,2-dipalmitoyl-sn-glycerol- 3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycerol- 3-phosphoethanolamine (DOPE-PEG, MW2000) and cholesterol using the ethanol injection technique and syringe pump. The NLs were characterized for their particle size, polydispersity index (PDI), and zeta potential using Malvern Zetasizer. The assay, unentrapped Camo using Vivaspin 500 ultrafilter (10 kDa) and in-vitro release were determined. The Camo content was analyzed using a validated HPLC method. The aerodynamic properties of Camo-pegNLs were determined using a Westech Andersen Cascade Impactor (ACI) at 28.3L/min and a pneumatic jet nebulizer. The antiviral effect of Camo-pegNLs was assessed in Vero cells expressing TMPRSS2 and infected with SARS-CoV- 2. Camo-pegNLs suspension showed size of 167.50 ± 0.90 nm, zeta potential of 0.48 ± 0.04 mV, and PDI of 0.07 ± 0.01. The quantity of entrapped Camo was found to be 44.86 ± 1.35%w/v, and the drug loading was 27.41 ± 0.04%w/w. The Camo-pegNL- 2 had an extended release of up to 24 h, MMAD of 4.295 ± 0.1 µm, GSD of 1.915 ± 0.064, and FPF of 42.01% ± 6.90. Camo-pegNLs showed a significant antiviral effect on Vero cells compared to no treatment group (<i>p</i> < 0.01). An efficacious nebulized Camo-pegNLs suspension product was successfully developed for direct lung delivery to Camo-pegNLs to treat the SARS-CoV- 2 infection.</p><h3>Graphical Abstract</h3><p>SARS-CoV- 2</p>\\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":6925,\"journal\":{\"name\":\"AAPS PharmSciTech\",\"volume\":\"26 5\",\"pages\":\"\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-05-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://link.springer.com/content/pdf/10.1208/s12249-025-03099-3.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"AAPS PharmSciTech\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1208/s12249-025-03099-3\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"AAPS PharmSciTech","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1208/s12249-025-03099-3","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Formulation and In-Vitro Testing of Nebulized Camostat Mesylate Loaded Nanoliposomes for the Treatment of SARS-CoV- 2 Infection
COVID- 19, caused by the coronavirus SARS-CoV- 2, has arisen as a global health epidemic, claiming the lives of millions of people throughout the world. Combating the pandemic has involved developing and approving vaccines and antiviral products. Camostat Mesylate (Camo) is a TMPRSS2 inhibitor that inhibits virus-cell membrane fusion and, thereby, viral multiplication. Significant limitations of using oral Camo include the limited amount of Camo reaching the site of action, lungs, side effects due to distribution to all tissues, and enzymatic breakdown in the gut. This investigation aims to develop self-administrable and patient-compliant extended-release Camo-loaded pegylated nanoliposomes (Camo-pegNLs) for delivering Camo directly to the lungs, thereby enabling faster onset of action and overcoming limitations of oral Camo delivery. We developed the Camo-pegNLs were composed of 1,2-dipalmitoyl-sn-glycerol- 3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycerol- 3-phosphoethanolamine (DOPE-PEG, MW2000) and cholesterol using the ethanol injection technique and syringe pump. The NLs were characterized for their particle size, polydispersity index (PDI), and zeta potential using Malvern Zetasizer. The assay, unentrapped Camo using Vivaspin 500 ultrafilter (10 kDa) and in-vitro release were determined. The Camo content was analyzed using a validated HPLC method. The aerodynamic properties of Camo-pegNLs were determined using a Westech Andersen Cascade Impactor (ACI) at 28.3L/min and a pneumatic jet nebulizer. The antiviral effect of Camo-pegNLs was assessed in Vero cells expressing TMPRSS2 and infected with SARS-CoV- 2. Camo-pegNLs suspension showed size of 167.50 ± 0.90 nm, zeta potential of 0.48 ± 0.04 mV, and PDI of 0.07 ± 0.01. The quantity of entrapped Camo was found to be 44.86 ± 1.35%w/v, and the drug loading was 27.41 ± 0.04%w/w. The Camo-pegNL- 2 had an extended release of up to 24 h, MMAD of 4.295 ± 0.1 µm, GSD of 1.915 ± 0.064, and FPF of 42.01% ± 6.90. Camo-pegNLs showed a significant antiviral effect on Vero cells compared to no treatment group (p < 0.01). An efficacious nebulized Camo-pegNLs suspension product was successfully developed for direct lung delivery to Camo-pegNLs to treat the SARS-CoV- 2 infection.
期刊介绍：
AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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