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.
Highlights
Silk has been used for centuries as fabric as well as in cosmeceutics
We investigated whether the novel and biologically-inspired silk-based drug delivery systems are suitable for inhalation to achieve deposition in the lower airways
The results indicate that this silk-based drug delivery system has the potential to be used in the targeted treatment of lung cancer
Summary
Silk has been used for centuries as fabric as well as in cosmeceutics It is recently attracting immense attention in biomedical applications[1]. A few recent studies highlight the advantages of combining silk fibroin with other bioactive materials such as albumin, chitosan, hyaluronic acid, polyprolactone and aloe vera in drug delivery and tissue engineering applications[8,9,10,11]. Despite the broad use of silk in biomedical applications, its potential as drug carriers for targeted delivery to the lungs is not investigated and silk-based delivery systems are yet to be developed into an inhalable form. This study aims to develop novel, biologically-inspired silk-based inhalable drug delivery systems that target the lungs. The lung is an attractive target for drug delivery due to the avoidance of first-pass metabolism, the large surface area and the rapid onset of action leading to enhanced absorption of drugs[13,15,16]
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