Sublingual Administration of Teucrium Polium-Loaded Nanofibers with Ultra-Fast Release in the Treatment of Diabetes Mellitus: In Vitro and In Vivo Evaluation.

In this study, Teucrium polium (TP) methanolic extract, which has antidiabetic activity and protects the ß-cells of the pancreas, was loaded in polyethylene oxide/sodium alginate nanofibers by electrospinning and administered sublingually to evaluate their effectiveness in type-2 diabetes mellitus (T2DM) by cell culture and in vivo studies. The gene expressions of insulin, glucokinase, GLUT-1, and GLUT-2 improved in TP-loaded nanofibers (TPF) on human beta cells 1.1B4 and rat beta cells BRIN-BD11. Fast-dissolving (<120 s) sublingual TPF exhibited better sustainable anti-diabetic activity than the suspension form, even in the twenty times lower dosage in streptozotocin/nicotinamide-induced T2DM rats. The levels of GLP-1, GLUT-2, SGLT-2, PPAR-γ, insulin, and tumor necrosis factor-alpha were improved. TP and TPF treatments ameliorated morphological changes in the liver, pancreas, and kidney. The fiber diameter increased, tensile strength decreased, and the working temperature range enlarged by loading TP in fibers. Thus, TPF has proven to be a novel supportive treatment approach for T2DM with the features of being non-toxic, easy to use, and effective.

Investigation of the effect of pancreatic decellularized matrix on encapsulated Islets of Langerhans with mesenchymal stem cells.

OBJECTIVE: In this study, it was aimed to provide a therapeutic approach for T1DM by encapsulating the pancreatic islets with mesenchymal stem cells and decellularized pancreatic extracellular matrix to support the survival of islets while maintaining their cellular activity. METHOD: Pancreatic extracellular matrix was decellularized using different concentrations of detergent series. After the preparation of the protein-based tissue extracellular matrix was shown to be free of cells or any genetic material by molecular, immunofluorescence and histochemical techniques. Following the homogenization of the decellularized pancreatic extracellular matrix and the analysis of its protein composition by LC-MS, the matrix proteins were incorporated with pancreatic islets and rat adipose tissue-derived MSCs (rAT-MSCs) in alginate microcapsules. Glucose-stimulated insulin secretion property of the islet cells in the microbeads was evaluated by insulin ELISA. The gene expression profile of the encapsulated cells was analyzed by Real-Time PCR. RESULTS: Unlike the protein composition of whole pancreatic tissue, the decellularized pancreas matrix was free of histone proteins or proteins originated from mitochondria. The protein matrix derived from pancreatic tissue was shown to support the growth and maintenance of the islet cells. When compared to the non-encapsulated pancreatic islet, the encapsulated cells demonstrate to be more efficient in terms of insulin expression. CONCLUSION: The extracellular pancreatic matrix obtained in this study was directly used as supplementary in the alginate-based microcapsule enhancing the cell survival. The tissue matrix protein and alginate had a synergistic effect on total insulin secretion, which might have the potential to overcome the insulin deficiency. Despite the improvement in the cell viability and the number, the efficiency of the insulin secretion in response to glucose stimulation from the alginate microcapsules did not meet the expectation when compared with the non-encapsulated pancreatic islets.

A novel multi-target strategy for Alzheimer's disease treatment via sublingual route: Donepezil/memantine/curcumin-loaded nanofibers.

Drug delivery systems that not only show efficacy through multiple therapeutic pathways but also facilitate patient drug use and exhibit a high bioavailability profile represent a promising strategy in the treatment of Alzheimer's disease (AD). Here, donepezil (DO)/memantine (MM)/curcumin (CUR)-loaded electrospun nanofibers (NFs) were produced for the treatment of AD. DSC, XRD, and FT-IR studies demonstrated the complete incorporation of the drug into PVA/PVP NFs. The disintegration profile was improved by loading the drugs in PVA/PVP with fast wetting (less than 1 s), the start of disintegration (21 s), and dispersion in 110 s. The desired properties for sublingual application were achieved with the dissolution of NFs in 240 s. The cell viability in DO/MM/CUR-loaded NFs was similar to the control group after 48 h in the cell culture. DO/MM/CUR-loaded NFs enhanced the expressions of BDNF (13.5-fold), TUBB3 (8.9-fold), Neurog2 (5.6-fold), NeuroD1 (5.8-fold), Nestin (166-fold), and GFAP (115-fold). DO/MM/CUR-loaded NFs and powder of these drugs contained in these fibers were daily administered sublingually to intracerebroventricular-streptozotocin (icv-STZ) treated rats. DO/MM/CUR-loaded NFs treatment improved the short-term memory damage and enhanced memory, learning ability, and spatial exploration talent. Results indicated that the levels of Aß, Tau protein, APP, GSK-3ß, AChE, and TNF-α were significantly decreased, and BDNF was increased by DO/MM/CUR-loaded NFs treatment compared to the AD group. In the histopathological analysis of the hippocampus and cortex, neuritic plaques and neurofibrillary nodes were not observed in the rats treated with DO/MM/CUR-loaded NFs. Taken together, the sublingual route delivery of DO/MM/CUR-loaded NFs supports potential clinical applications for AD.

Improvement of the insulin secretion from beta cells encapsulated in alginate/poly-L- histidine/alginate microbeads by platelet-rich plasma.

Type 1 diabetes is clinically characterized as the loss of control of glucose homeostasis due to the reduced number of insulinproducing cells. Long-term glycemic control after implantation could be maintained by preserving the cell viability and tissue-specific functions during the process of microencapsulation. In this study, alginate solution was supplemented with platelet-rich plasma (PRP) to improve the viability and preserve the cell functions during the encapsulation of a beta cell line (BRIN-BD11). Cell viability was assessed and insulin secretion and insulin stimulation index were evaluated. eTh polymerization of alginate with PRP enhanced the viability up to 61% in the alginate microbeads. PRP supplementation to the alginate composition not only increased the number of viable cells by 1.95-fold, but the insulin secretion also improved by about 66%. eTh stimulation index, however, was not affected by the PRP supplementation.