Pulmonary Insulin-like Growth Factor I Delivery from Trehalose and Silk-Fibroin Microparticles

Abstract

Insulin-like growth factor I (IGF-I) is a strong anabolic peptide with promising therapeutic value in muscle wasting diseases such as sarcopenia. We report a pulmonary IGF-I delivery system deploying silk-fibroin (SF) as carrier and in comparison to trehalose. Both IGF-I delivery systems were characterized regarding IGF-I integrity, IGF-I release profiles and aerodynamic properties. Transepithelial in vitro transport of IGF-I using the pulmonary Calu-3 model cell system followed comparable kinetics and mechanism of uptake as earlier demonstrated for insulin (INS), for which effective pulmonary delivery is known. Microparticles were spray-dried using either trehalose or SF, resulting in geometries allowing alveolar deposition. The effective IGF-I shuttling through the epithelial barrier of the lung was demonstrated in an ex vivo human lung lobe model, and expanded the exciting possibility of this administration route to this effective and anabolic peptide.

Nano Spray-Dried Drugs for Oral Administration: A Review

“…21,78 As several studies have shown, nano spray drying has only a negligible or marginal influence on product degradation or aggregation. For example, Schultz et al 79 revealed that the activity of insulin-like growth factor encapsulated in trehalose remained unaffected. In another study, Schmid detected a slight decrease in L-lactic dehydrogenase enzyme activity during feed pump circulation.…”

From silk spinning in insects and spiders to advanced silk fibroin drug delivery systems

“…Furthermore, circular dichroism was used (vide supra) [90]. Additionally, morphological changes of solid SF scaffolds or particles can be observed upon crystallization, typically including shrinkage of scaffolds, changes in porosity [41] or altered surface roughness [29,92]. Methanol is typically used to induce the crystallinity [90] through SF dehydration and conformational destabilizing leading to b-sheet formation [41].…”

Cryo-crystallization under a partial anti-solvent environment as a facile technology for dry powder inhalation development

“…28,29 In case of non spherical particles, particularly elongated ones, the aspect ratio plays a key role. It is a fact that the cross sectional area of air way from trachea to alveoli decreases progressively causing enormous air resistance during inhalation.…”

“…the alveoli. 28,29 In the case of non spherical particles, particularly elongated ones, the aspect ratio plays a key role. If the smaller dimension (width or thickness) of the elongated particles is below 5 mm, they will reach the alveoli.…”