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.

Implantable chemotherapy-loaded silk protein materials for neuroblastoma treatment

“…Silk fibroin‐based materials have gained considerable interest in supporting the bioactivity and delivery of many therapeutic molecules including oncology therapeutics . Additionally, silk protein‐based materials have been used clinically for centuries as a suture material and more recently has gained FDA approval as a bioresorbable scaffold for soft tissue support and to reinforce tissue deficiencies .…”

“…7 Silk fibroin-based materials have gained considerable interest in supporting the bioactivity and delivery of many therapeutic molecules including oncology therapeutics. [8][9][10][11][12][13][14][15][16][17] Additionally, silk protein-based materials have been used clinically for centuries as a suture material and more recently has gained FDA approval as a bioresorbable scaffold for soft tissue support and to reinforce tissue deficiencies. 18 Furthermore, materials developed from silk fibroin isolated from Bombyx mori silkworm cocoons exhibit minimal immune response in vivo, 19,20 are fully biodegradable 19,21 and is processed via all aqueous techniques.…”

Characterization of drug delivery vehicles using atomic force microscopy: current status

“…Surface roughness values were obtained from AFM images of spray-dried and spray-freeze-dried silkbased nanoparticles; the latter had much larger values (Ra 421 c.f. 27 nm) and were therefore judged more favourable for improved dispersion and enhanced aerosolisation efficiency for their use as lung cancer delivery agents (encapsulating cisplatin) [78].…”

Sustained release silk fibroin discs: Antibody and protein delivery for HIV prevention

“…Silk fibroin doesn't cause any inflammatory reaction and biocompatible following degumming process and therefore it can safely be applied via vaginal or rectal routes [8,9]. In addition to being a Food and Drug Administration (FDA) approved biomaterial as medical sutures and soft tissue scaffolds [10], silk has shown the ability to successfully deliver a wide range of bioactive molecules including antineoplastic drugs [11][12][13][14][15][16][17][18], antibiotics [19], antiepileptics [20], genes [21,22] and biological drugs such as growth factors [23] and antibodies [24]. Silk also increases the stability of drugs and biomacromolecules [25][26][27].…”