RESUMEN
In vivo evaluation of arabinoxylans (AX) microspheres showed to protect insulin from degradation in the upper gastrointestinal tract and carrier insulin to colon. Insulin-loaded AX microspheres (50 UI/kg) decreased blood glucose level by 39% in diabetic rats with a maximum effect at 18 h post-administration, indicating that insulin remains bioactive. The continuous administration (4 days) of insulin-loaded AX microspheres improved the polyuria and increased the production of short-chain fatty acids, as well as Bifidobacterium and Bacteroides in diabetic rats compared to untreated diabetic rats. AX microspheres are a potential microbiota-activated carrier for colon-specific drug delivery and could be useful as a complementary treatment for diabetes.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Portadores de Fármacos/metabolismo , Microbioma Gastrointestinal , Insulina/administración & dosificación , Xilanos/metabolismo , Administración Oral , Animales , Colon/metabolismo , Colon/microbiología , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/microbiología , Diabetes Mellitus Tipo 1/inducido químicamente , Diabetes Mellitus Tipo 1/microbiología , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/microbiología , Humanos , Insulina/farmacocinética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Masculino , Microesferas , Ratas , Estreptozocina/administración & dosificación , Estreptozocina/toxicidadRESUMEN
Arabinoxylans (AX) microspheres with different insulin/AX mass ratio were prepared by formation of phenoxy radical issued from the ferulic acid by enzymatic oxidation (entrapped in situ of insulin). Phenolic acid content and FT-IR spectrum of unloaded and insulin-loaded AX microspheres revealed that the phenoxy radical issued from the ferulic acid by enzymatic oxidation did not interact covalently with insulin. The microspheres showed a spherical shape, smooth surface and an average diameter of particles of 320⯵m. In vitro control release found that AX microspheres minimized the insulin loss in the upper GI tract, retaining high percentage (~75%) of insulin in its matrix. The stability of the secondary structure of insulin was studied by dichroism circular (CD). The CD spectra of insulin released from AX microspheres did not change according to the insulin/AX mass ratio of the microsphere. Significant hypoglycemic effects with improved insulin-relative bioavailability tested on an in vivo murine model revealed the efficacy of these enzymatically cross-linked arabinoxylans microspheres as a new oral insulin carrier.