title: Formulation of Biologically-Inspired Silk-Based Drug Carriers for Pulmonary Delivery Targeted for Lung Cancer.
abstract: The benefits of using silk fibroin, a major protein in silk, are widely established in many biomedical applications including tissue regeneration, bioactive coating and in vitro tissue models. The properties of silk such as biocompatibility and controlled degradation are utilized in this study to formulate for the first time as carriers for pulmonary drug delivery. Silk fibroin particles are spray dried or spray-freeze-dried to enable the delivery to the airways via dry powder inhalers. The addition of excipients such as mannitol is optimized for both the stabilization of protein during the spray-freezing process as well as for efficient dispersion using an in vitro aerosolisation impactor. Cisplatin is incorporated into the silk-based formulations with or without cross-linking, which show different release profiles. The particles show high aerosolisation performance through the measurement of in vitro lung deposition, which is at the level of commercially available dry powder inhalers. The silk-based particles are shown to be cytocompatible with A549 human lung epithelial cell line. The cytotoxicity of cisplatin is demonstrated to be enhanced when delivered using the cross-linked silk-based particles. These novel inhalable silk-based drug carriers have the potential to be used as anti-cancer drug delivery systems targeted for the lungs.
authors.affiliation: 1] Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia [2] Department of Biochemical Engineering, University College London, London WC1E7JE, United Kingdom.
authors.forename: Sally Yunsun
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, West Bengal - 721302, India.
authors.forename: Deboki
authors.initials: D
authors.lastname: Naskar
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, West Bengal - 721302, India.
authors.forename: Subhas C
authors.initials: SC
authors.lastname: Kundu
authors.affiliation: Elemental Bio-imaging Facility, University of Technology Sydney, Broadway, NSW, 2007, Australia.
authors.forename: David P
authors.initials: DP
authors.lastname: Bishop
authors.affiliation: Elemental Bio-imaging Facility, University of Technology Sydney, Broadway, NSW, 2007, Australia.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Doble
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Alan V
authors.initials: AV
authors.lastname: Boddy
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
authors.affiliation: 1] Department of Biochemical Engineering, University College London, London WC1E7JE, United Kingdom [2] Department of Nanobiomedical Science &BK21 Plus NBM Global Research Center of Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Ivan B
authors.initials: IB
authors.lastname: Wall
authors.affiliation: 1] Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia [2] Department of Nanobiomedical Science &BK21 Plus NBM Global Research Center of Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Chrzanowski
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry* / Q000633:toxicity; D001672:Biocompatible Materials / Q000737:chemistry*; D012831:Bombyx / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry* / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D058995:Dry Powder Inhalers / Q000379:methods; D005349:Fibroins / Q000737:chemistry* / Q000302:isolation & purification; D005612:Freeze Drying; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size
chemical_list: D018906:Antineoplastic Agents, Alkylating; D001672:Biocompatible Materials; D004337:Drug Carriers; D005349:Fibroins; D002945:Cisplatin