Evaluation of novel particles as pulmonary delivery systems for insulin in rats

Abstract

KEYWORDS:pulmonary delivery, insulin, CAP-PEG particles, pharmacokinetics, pharmacodynamicsThe purpose of the study was to evaluate the influence of calcium phosphate (CAP) and polyethylene glycol (PEG) particles on the systemic delivery of insulin administered by the pulmonary route. Two methods of pulmonary delivery were employed: intratracheal instillation and spray instillation. Insulin-CAP-PEG particles in suspension (1.2 U/kg, 110-140 μL) were administered to the lungs of fasted rats by intratracheal instillation (INCAPEG) or spray instillation (SINCAPEG). Control treatments consisted of insulin solution (1.2 U/kg) by intratracheal instillation, spray instillation, and subcutaneous administration (SC). Plasma concentrations of insulin and glucose were determined by chemiluminescence and colorimetric methods, respectively. Data were analyzed by compartmental and non-compartmental methods, and pharmacokinetic (PK) and pharmacodynamic (PD) parameters of insulin disposition were determined. PK analysis suggested that insulin administered in particles had a longer half-life, a longer mean residence time, and a smaller rate of elimination than insulin in solution. In addition, insulin bioavailability after SINCAPEG was 1.8-fold that of insulin solution administered SC. PD analysis showed that smaller areas under the effect curve and, conversely, larger areas above the effect curve were obtained after INCAPEG in comparison to insulin solution. The magnitude of this effect was increased after SINCAPEG. The presence of CAP-PEG particles appears to positively influence the disposition of insulin administered to the lungs of Sprague-Dawley rats. Spray instillation appears to be a more efficient method of delivering insulin to the lungs of rats than intratracheal instillation.

In vivo animal models for drug delivery across the lung mucosal barrier☆

“…The objectives of the analysis of drug action are to delineate the chemical or physical interactions between a drug and the target cell and to characterize the full sequence and scope of actions of each drug [136]. Studies that evaluate the disposition of [103,105]. These studies measured the decrease in glucose levels after administration of insulin formulations.…”

The Effect of Salvia Hispanica L. Seeds on Weight Loss in Overweight and Obese Individuals with Type 2 Diabetes Mellitus

“…Insulin was separated from the samples using immunoprecipitation with magnetic particles, and subsequently reacted with a chemiluminescent substrate to generate light (231). The light generated was directly proportional to the concentration of insulin in the sample, as measured using a luminometer and determined from a calibration curve (231).…”

Nanoparticle Insulin Drug Delivery — Applications and New Aspects

“…Low frequency ultrasound (20-160 kHz) decreases blood glucose levels both in animal and human studies [36,72,75].…”

“…When aerolized insulin liposomes delivered by the inhalation route in mice caused significantly reduction in plasma glucose concentrations [71]. Insulincalcium phosphate (CAP) and polyethylene glycol (PEG) particles were administered to the lungs by a route of administration of respiratory tract and these particles positively affected the disposition of the insulin in the lungs of rats [72]. Poly-lactide-co-glycolide (PLGA) particles have used to improve insulin loaded particles which has a mean diameter of 400 nm.…”