Formulation of Biologically-Inspired Silk-Based Drug Carriers for Pulmonary Delivery Targeted for Lung Cancer

Sally Yunsun Kim, Deboki Naskar, Subhas C Kundu, David P Bishop, Philip A Doble, Alan V Boddy, Hak-Kim Chan, Ivan B Wall, Wojciech Chrzanowski

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number11878
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 3 Aug 2015

Bibliographical note

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Keywords

  • Animals
  • Antineoplastic Agents, Alkylating/chemistry
  • Biocompatible Materials/chemistry
  • Bombyx/metabolism
  • Cell Line, Tumor
  • Cell Movement/drug effects
  • Cell Proliferation/drug effects
  • Cell Survival/drug effects
  • Cisplatin/chemistry
  • DNA Damage/drug effects
  • Drug Carriers/chemistry
  • Dry Powder Inhalers/methods
  • Fibroins/chemistry
  • Freeze Drying
  • Humans
  • Nanoparticles/chemistry
  • Particle Size

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