How it Works
We believe the rapid action of Technosphere® Insulin may be related to unique characteristics of both our carrier molecule and the insulin in our formulation. Our Technosphere® formulation technology is centered on a class of pH-sensitive organic molecules, known as fumaryl diketopiperazine (FDKP), that self-assemble into small particles under mildly acidic conditions.
Certain drugs, such as insulin, can be loaded onto these particles by combining mildly acidic solutions of the drug and FDKP to form a mixture, which is then dried to form a powder. This powder is then filled into plastic cartridges and blister-packaged. To obtain a dose of insulin, a patient loads a cartridge into our palm-sized inhaler. By inhaling through the inhaler, air is pulled through the cartridge, which breaks up the powder and pulls the particles into the air current and out through the mouthpiece. The individual particles within this powder are small and have a highly porous surface topography; these qualities enable them to fly deep into the lungs.
When the particles contact the moist lung surface with its neutral pH, the Technosphere® particles instantaneously change from a powder to a liquid, releasing the insulin molecules to diffuse across a thin layer of cells into the bloodstream. This final step occurs passively, without any active assistance or enhancement. Technosphere® particles, unlike penetration enhancers, do not affect the tight junctions between cells, do not alter cell permeability and do not cause disruption of cell membranes.
Moreover, when the Technosphere® particles dissociate, it appears that the insulin that is released is in a form that can readily be used by the body. In most pharmaceutical dosage forms, regular human insulin exists as a hexamer, a complex of six associated insulin molecules. In order to exert a pharmacological effect, the hexamer must first dissociate into three dimers — complexes of two insulin molecules — which then further dissociate into individual insulin molecules, or monomers. Only monomeric insulin exerts a physiological effect. Rapid-acting insulin analogs are designed to be fragile hexamers that dissociate more quickly than regular insulin, thereby reducing the time required to achieve an effect. However, the insulin released from Technosphere® particles is already largely in monomeric form. During the manufacture of Technosphere® Insulin, we cause hexameric insulin to dissociate into monomeric insulin before being loaded onto Technosphere® particles. When the Technosphere® Insulin particles dissolve in the deep lung, the insulin that is released is a mixture of dimer and monomer. Little change to the insulin is required before it can start exerting its glucose-lowering effect.
