The current study aimed at developing diethonolamine-modified high-methoxyl pectin (DMP)-alginate (ALG) based core-shell composites for controlled intragastric delivery of metformin HCl (MFM) by combined approach of floating and bioadhesion. DMP with degree of amidation of 48.72% was initially accomplished and characterized by FTIR, DSC and XRD analyses. MFM-loaded core matrices were then fabricated by ionotropic gelation technique employing zinc acetate as cross-linker. The core matrices were further coated by fenugreek gum (FG)-ALG gel membrane via diffusion-controlled interfacial complexation method. Various formulations demonstrated excellent drug encapsulation efficiency (DEE, 51-70%) and sustained drug eluting behavior (Q8h, 72-96%), which were extremely influenced by polymer-blend (ALG:DMP) ratios, low density additives (olive oil/magnesium stearate) and FG-ALG coating inclusion. The drug release profile of the core-shell matrices (F-7) was best fitted in zero-order kinetic model with case-II transport driven mechanism. It also portrayed outstanding gastroretentive characteristics. Moreover, the composites were analyzed for surface morphology, drug-excipients compatibility, thermal behavior and drug crystallinity. Thus, the developed composites are appropriate for controlled stomach-specific delivery of MFM for type 2 diabetes management.
High-fat diet (HFD) interferes with the dietary plan of patients with type 2 diabetes mellitus (T2DM). However, many diabetes patients consume food with higher fat content for a better taste bud experience. In this study, we examined the effect of HFD on rats at the early onset of diabetes and prediabetes by supplementing their feed with palm olein oil to provide a fat content representing 39% of total calorie intake. Urinary profile generated from liquid chromatography-mass spectrometry analysis was used to construct the orthogonal partial least squares discriminant analysis (OPLS-DA) score plots. The data provide insights into the physiological state of an organism. Healthy rats fed with normal chow (NC) and HFD cannot be distinguished by their urinary metabolite profiles, whereas diabetic and prediabetic rats showed a clear separation in OPLS-DA profile between the two diets, indicating a change in their physiological state. Metformin treatment altered the metabolomics profiles of diabetic rats and lowered their blood sugar levels. For prediabetic rats, metformin treatment on both NC- and HFD-fed rats not only reduced their blood sugar levels to normal but also altered the urinary metabolite profile to be more like healthy rats. The use of metformin is therefore beneficial at the prediabetes stage.