Effect of matrix composition, sphere size and hormone concentration on diffusion coefficient of insulin for controlled gastrointestinal delivery for diabetes treatment

Abstract

Oral insulin administration is limited due to its degradation by proteases. The hormone was encapsulated in spheres made of either pure calcium alginate (ALG) or its association with whey protein isolate (WPI-ALG) in order to minimise loss in the stomach region while allowing liberation in the maximum absorption area, located in the intestine. Diffusion coefficients for both matrix compositions were determined in vitro for gastric pH (5.88 and 10.26 × 10 m s) and intestinal pH (21.11 and 79.29 × 10 m s). Higher initial insulin concentrations and lower diameters accelerated its release, confirming Fickian behaviour. The analytic model exhibited a good fit in most cases. Computer simulations revealed that ALG spheres are more convenient for oral administration because they release more insulin in the intestine than the WPI-ALG ones, thus supporting its therapeutic viability for the purpose of reducing stress in those who depend on insulin.

Photoacoustic imaging reveals mechanisms of rapid-acting insulin formulations dynamics at the injection site

“…Moreover, the in vivo diffusion analysis shows that excipients do influence protein transport by enabling faster diffusion in the interstitium. Until now, all the reported studies on diffusion of therapeutic insulins have been performed in either water, gel-based phantoms, or ex vivo [ 25 , 39 , 40 ]. Our in vivo study accounts for crucial diffusion factors, such as interstitium pressure on the drug from tissue elasticity, the effect of interstitial fluid viscosity, and tissue heterogeneity that were not properly controlled for in the past studies and suggests a further study to understand the translation of this mouse ear cutaneous model to the human subcutaneous tissue.…”