Alternative mechanisms of insulin delivery
The need for insulin delivery not based on syringe and needle derives from problems associated with control of diabetes by this method. These include dislike of injections producing poor compliance; adverse insulin pharmacokinetics (basal insulin not constant, sc absorption of short-acting insulin too slow, highly variable absorption); hyperinsulinaemia due to peripheral rather than portal administration; and lack of feedback control due to absence of continuous glucose sensing.
Approaches to solving these problems include the development of inhaled insulin which, because it is absorbed (with low bioavailability) from the alveoli with their surface area 70 times that of the body, has an early peak action of about 30 min. It is therefore best given at meal-times. Mechanical and electronically controlled devices administer the inhaled insulin as an aerosolized dry powder or solution. In preliminary trials it is associated with improved patient satisfaction.
Oral insulin formulations have a long history, attempting to overcome protein denaturation, proteolytic degradation and low gut permeability. Some technologies investigated include insulin entrapped in liposomes (where absorption is enhanced but unpredictable), incorporation of insulin in biodegradable polymeric particles and 'drug carriers' such as bile acids. A recent experimental strategy for increasing intestinal insulin absorption is to enhance the permeability of the paracellular tight junction with zonula occludens toxin, a protein from Vibrio cholera.
Transdermal insulin administration via by low-frequency ultrasound and photomechanical waves is also being studied for increasing absorption across the stratum corneum.
Portable infusion pumps are now part of established clinical practice. The challenge is to 'close the loop' by coupling the pump to a glucose sensor. The stability and accuracy of in vivo glucose sensors has been a major problem in recent years. However, there is active investigation of alternative technologies, including non-invasive methods such as fluorescence which might prove robust enough for clinical use.