Intranasal Aerosolized Insulin

Abstract

We assessed the efficacy of intranasal aerosolized insulin containing laureth-9 as a surfactant in patients with Type I diabetes by fasting studies in 8 patients, mixed-meal studies in 15, and long-term home use in 8. The intranasal insulin (1 U per kilogram of body weight in 1 per cent laureth-9) was rapidly absorbed (in 15 minutes); it lowered the plasma glucose level by 50 per cent in 45 minutes in fasting normal controls and by 50 per cent in 120 minutes in fasting diabetics. The glucose-lowering potency depended on the insulin dose and surfactant concentration. Nasal irritation was proportional to surfactant concentration, with great variability among subjects. After intranasal insulin used before meals (1 U per kilogram in 1 per cent laureth-9), the two-hour postprandial glucose level increased above before-meal levels by 38 mg per deciliter, as compared with 191 mg per deciliter after intranasal placebo in patients with Type I diabetes (P less than 0.05). An outpatient feasibility study examining three months of use of intranasal aerosolized insulin before meals as a supplement to Ultralente insulin revealed that the aerosol was well tolerated, with glycemic control (as indicated by the percentage of glycohemoglobin, home glucose measurements, and hypoglycemic reactions) comparable to that during a subsequent three-month period of conventional subcutaneous insulin treatment. The results suggest that intranasal insulin has potential as an adjunct to subcutaneous insulin in the therapy of Type I diabetes.

Effect of Brij-78 on Systemic Delivery of Insulin from an Ocular Device

“…Chiou et al 3 showed no irritation in the peripheral tissue of eye due to 50 µL of 0.25% insulin eyedrops containing 0.5% of Brij-78. In addition, Salzman et al 21 pointed out that 0.1% laureth-9 (polyoxyethylene-9 lauryl ether) in intranasal spray insulin was completely tolerated in all of the study subjects. On the other hand, some preliminary studies 22,23 regarding insulin intranasal systemic delivery have indicated that the absorption enhancer will irritate the nasal mucosa.…”

Insulin structure and function

“…Nonetheless, nasal insulin delivery can be achieved through the use of absorption enhancers at a bioavailability similar to that recorded for pulmonary delivery (*5-10%). 201,202 These additives, which include such entities as phosphotidylcholine derivatives, 203 laureth-9, 204 and bile salts, 205 have been associated with acute and chronic nasal irritation. Finding the right combination of insulin and absorption enhancer that provides efficacy with little adverse effect remains the central challenge for this route of administration.…”

Intrapulmonary administration of insulin to healthy volunteers

“…In contrast to our study, earlier investigations on intrapulmonary and intranasal insulin administration have not been randomized, nor blinded and the materials have also been fairly small with as few as six subjects receiving treatment on only one occasion [10,11], except for Salzman et al who investigated a total of 45 patients with insulindependent diabetes mellitus (IDDM) [12].…”