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Article: Inhalable powder formulations of siRNA and pH responsive peptides with antiviral activity against H1N1 influenza virus

TitleInhalable powder formulations of siRNA and pH responsive peptides with antiviral activity against H1N1 influenza virus
Authors
Issue Date2015
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/mpohbp/index.html
Citation
Molecular Pharmaceutics, 2015, v. 12 n. 3, p. 910-921 How to Cite?
Abstract(Graph Presented) Pulmonary delivery of siRNA has considerable therapeutic potential for treating viral respiratory infectious diseases including influenza. By introducing siRNA that targets the conserved region of viral genes encoding nucleocapsid protein (NP), viral mRNAs can be degraded and viral replication can be inhibited in mammalian cells. To enable siRNA to be used as an antiviral agent, the nucleic acid delivery barrier must be overcome. Effective local delivery of siRNA to lung tissues is required to reduce the therapeutic dose and minimize systemic adverse effects. To develop a formulation suited for clinical application, complexes of pH-responsive peptides, containing either histidine or 2,3-diaminopropionic acid (Dap), and siRNA were prepared into dry powders by spray drying with mannitol, which was used as a bulking agent. The spray-dried (SD) powders were characterized and found to be suitable for inhalation with good stability, preserving the integrity of the siRNA as well as the biological and antiviral activities. The formulations mediated highly effective in vitro delivery of antiviral siRNA into mammalian lung epithelial cells, leading to significant inhibition of viral replication when the transfected cells were subsequently challenged with H1N1 influenza virus. SD siRNA powders containing pH-responsive peptides are a promising inhalable formulation to deliver antiviral siRNA against influenza and are readily adapted for the treatment of other respiratory diseases. © 2015 American Chemical Society.
Persistent Identifierhttp://hdl.handle.net/10722/208766
ISSN
2015 Impact Factor: 4.342
2015 SCImago Journal Rankings: 1.681

 

DC FieldValueLanguage
dc.contributor.authorLIANG, W-
dc.contributor.authorCHOW, YT-
dc.contributor.authorLau, PN-
dc.contributor.authorZhou, QT-
dc.contributor.authorKwok, PCL-
dc.contributor.authorLeung, GPH-
dc.contributor.authorMason, AJM-
dc.contributor.authorChan, HK-
dc.contributor.authorPoon, LLM-
dc.contributor.authorLam, JKW-
dc.date.accessioned2015-03-18T09:12:16Z-
dc.date.available2015-03-18T09:12:16Z-
dc.date.issued2015-
dc.identifier.citationMolecular Pharmaceutics, 2015, v. 12 n. 3, p. 910-921-
dc.identifier.issn1543-8384-
dc.identifier.urihttp://hdl.handle.net/10722/208766-
dc.description.abstract(Graph Presented) Pulmonary delivery of siRNA has considerable therapeutic potential for treating viral respiratory infectious diseases including influenza. By introducing siRNA that targets the conserved region of viral genes encoding nucleocapsid protein (NP), viral mRNAs can be degraded and viral replication can be inhibited in mammalian cells. To enable siRNA to be used as an antiviral agent, the nucleic acid delivery barrier must be overcome. Effective local delivery of siRNA to lung tissues is required to reduce the therapeutic dose and minimize systemic adverse effects. To develop a formulation suited for clinical application, complexes of pH-responsive peptides, containing either histidine or 2,3-diaminopropionic acid (Dap), and siRNA were prepared into dry powders by spray drying with mannitol, which was used as a bulking agent. The spray-dried (SD) powders were characterized and found to be suitable for inhalation with good stability, preserving the integrity of the siRNA as well as the biological and antiviral activities. The formulations mediated highly effective in vitro delivery of antiviral siRNA into mammalian lung epithelial cells, leading to significant inhibition of viral replication when the transfected cells were subsequently challenged with H1N1 influenza virus. SD siRNA powders containing pH-responsive peptides are a promising inhalable formulation to deliver antiviral siRNA against influenza and are readily adapted for the treatment of other respiratory diseases. © 2015 American Chemical Society.-
dc.languageeng-
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/mpohbp/index.html-
dc.relation.ispartofMolecular Pharmaceutics-
dc.titleInhalable powder formulations of siRNA and pH responsive peptides with antiviral activity against H1N1 influenza virus-
dc.typeArticle-
dc.identifier.emailLau, PN: sbsylvia@hku.hk-
dc.identifier.emailKwok, PCL: pclkwok@hku.hk-
dc.identifier.emailLeung, GPH: gphleung@hkucc.hku.hk-
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hk-
dc.identifier.emailLam, JKW: jkwlam@hku.hk-
dc.identifier.authorityKwok, PCL=rp01540-
dc.identifier.authorityLeung, GPH=rp00234-
dc.identifier.authorityPoon, LLM=rp00484-
dc.identifier.authorityLam, JKW=rp01346-
dc.identifier.doi10.1021/mp500745v-
dc.identifier.scopuseid_2-s2.0-84924039536-
dc.identifier.hkuros242636-
dc.identifier.volume12-
dc.identifier.issue3-
dc.identifier.spage910-
dc.identifier.epage921-
dc.publisher.placeUnited States-

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