Many protein-based drugs are administered by injection because of their low stability and bioavailability. Pulmonary delivery has been shown as non-invasive administration route to injection administration, while offering a higher storage stability as powder. However, in order to reach the lower airways, the aerodynamic particle size distribution requires µm size particles. The supercritical fluid (SC) drying is a fast and mild process suitable to produce microparticles (MPs) for inhalation, by protein precipitation in an anti-solvent process (SAS) with SC-CO2. Because MPs are very cohesive and characterized by poor flow properties, a common strategy involves blending the active compound with a carrier. Furthermore, the MPs can be engineered to achieve site specificity, like surface molecules receptors to improved targeting efficacy. Because approved excipients are very limited, interest is turning to natural materials, produced with rapid and mild methods, lower cost, and evidencing similar or higher biocompatibility profiles.
The microwave technology (MW), using the know-how already acquired by the team, will be applied to treat locust bean gum (galactomannans (GM) model), gum arabic (arabinogalactans (AG) model), coffee and spent coffee grounds (SCG). The advantage of using SCG is its content in GM and AG, but also chlorogenic acids and melanoidins which can confer charge and potentiate additional stability. The use of hot compressed water in MW systems, avoiding organic solvents, and the high water-solubility of these carbohydrates, pose two interesting properties for their use as natural polymers for engineering of new pulmonary delivery carriers. The water-soluble carbohydrates will be fractionated, purified, and structurally characterized using methodologies implemented in routine laboratory analysis obtaining a large range of carbohydrate structures (distinct degrees of polymerization, degrees of ramification, ratios mannose/galactose, etc). Microcarriers for target compound delivery, using insulin as protein model. The possibility to have negative charges using SCG melanoidins will increase the interaction with insulin to potentiate an increase sustained release. In vitro studies will clarify the kinetics and mechanisms of epithelial transport, evidencing microparticles bioactivity. Because both insulin and polysaccharides have a very low solubility in SC-CO2, SAS technique will be applied to obtain the loaded microparticles.