Growing evidences suggest the presence of several similarities in the molecular mechanisms underlying the neurodegenerative diseases and metabolic abnormalities. Adults who develop Metabolic Syndrome (MS) are at a higher risk of developing Alzheimer's disease (AD). Pharmacological agents, like dipeptidyl peptidase-4 (DPP-4) inhibitors that increase the levels of glucagon like peptide 1 (GLP-1) and ameliorate symptoms of MS, have become an auspicious candidate as disease modifying agents in the treatment of AD. The present study investigates the beneficial effects of Vildagliptin, a DPP-4 inhibitor in counteracting cognitive decline in different models of dementia targeting the AKT, JAK/STAT signaling pathways and hippocampal Klotho expression, to judge the neuroprotective, anti-apoptotic and anti-inflammatory effects of the drug. Cognitive decline was induced by either administration of high fat high sugar (HFHS) diet for 45 days alone, or with oral administration of AlCl (100 mg/kg/day) for 60 days. Rats were orally administered Vildagliptin (10 mg/kg) for 60 days along with AlCl administration. Vildagliptin treatment improved spatial memory and activities in morris water maze (MWM) test and open field test respectively. Results revealed an increase of both hippocampal klotho and Bcl-2 expressions along with an increase in both AKT and ERK1/2 phosphorylation. In contrast, Vildagliptin treatment decreased hippocampal contents of inflammatory, apoptotic and oxidative stress biomarkers as TNF-α, caspase-3 and FOXO1 along with restoring metabolic abnormalities. A significant decrease in BAX expressions with JAK2/STAT3 inhibition was observed. These findings demonstrate that the neuroprotective role of vildagliptin is possibly via modulating Klotho protein together with AKT pathway.

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One of the greatest challenges in in situ forming implant (ISFI) systems by polymer precipitation is the large burst release during the first 124 hours after implant injection. The aim of this study was to decrease the burst-release effect of a water-soluble model drug, donepezil HCl, with a molecular weight of 415.96Da, from in situ forming implants using a novel in situ implant containing lipospheres (ISILs). In situ implant suspensions were prepared by dispersing cetyl alcohol and glyceryl stearate lipospheres in a solution of poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG). Also, in situ implant solutions were prepared using different concentrations of PDL or PDLG solutions in N-methyl-2-pyrrolidone (NMP). Triacetin and Pluronic L121 were used to modify the release pattern of donepezil from the in situ implant solutions. In vitro release, rheological measurement, and injectability measurement were used to evaluate the prepared in situ implant formulae. It was found that ISIL decreased the burst effect as well as the rate and extent of drug release, compared to lipospheres, PDL, and PDLG in situ implant. The amount of drug released in the first day was 37.75, 34.99, 48.57, 76.3, and 84.82% for ISIL in 20% PDL (IL-1), ISIL in 20% PDLG (IL-2), lipospheres (L), 20% PDL ISFI (I5), and 20% PDLG ISFI (I8), respectively. The prepared systems showed Newtonian flow behavior. ISIL (IL-1 and IL-2) had a flow rate of 1.94 and 1.40mL/min, respectively. This study shows the potential of using in situ implants containing lipospheres in controlling the burst effect of ISFI. © 2012 Informa Healthcare USA, Inc.

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Paper-based microfluidic device was designed with wax-printing to combine potentiometric, fluorimetric and colorimetric detection zones. This newly developed trimodal paper chip has been used for on-site determination of ketamine hydrochloride (KET) as a date rape drug in beverages. The device employed polyaniline nano-dispersion as conducting polymer in ion sensing paper electrodes designed to fit USB plug connector. Carbon dots-gold nanoparticles and cobalt thiocyanate were used in fluorescence and color detection zones, respectively. Cellular phone’s camera facilitated the on-site fluorimetric and color detection. The implemented trimodal detection system exhibited specificity for KET detection in the presence of several other beverage interferences i.e., biogenic amines. This innovative sensor brings together analytical figures of merit for effective KET detection in single aliquot of spiked beverages. The proposed paper-based chip also fulfils WHO criteria for point-of-care devices posing the proposed trimodal paper device as an active part for rapid, on-site drug diagnostics and to be applied further for other similar drugs.

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One of the greatest challenges in in situ forming implant (ISFI) systems by polymer precipitation is the large burst release during the first 124 hours after implant injection. The aim of this study was to decrease the burst-release effect of a water-soluble model drug, donepezil HCl, with a molecular weight of 415.96Da, from in situ forming implants using a novel in situ implant containing lipospheres (ISILs). In situ implant suspensions were prepared by dispersing cetyl alcohol and glyceryl stearate lipospheres in a solution of poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG). Also, in situ implant solutions were prepared using different concentrations of PDL or PDLG solutions in N-methyl-2-pyrrolidone (NMP). Triacetin and Pluronic L121 were used to modify the release pattern of donepezil from the in situ implant solutions. In vitro release, rheological measurement, and injectability measurement were used to evaluate the prepared in situ implant formulae. It was found that ISIL decreased the burst effect as well as the rate and extent of drug release, compared to lipospheres, PDL, and PDLG in situ implant. The amount of drug released in the first day was 37.75, 34.99, 48.57, 76.3, and 84.82% for ISIL in 20% PDL (IL-1), ISIL in 20% PDLG (IL-2), lipospheres (L), 20% PDL ISFI (I5), and 20% PDLG ISFI (I8), respectively. The prepared systems showed Newtonian flow behavior. ISIL (IL-1 and IL-2) had a flow rate of 1.94 and 1.40mL/min, respectively. This study shows the potential of using in situ implants containing lipospheres in controlling the burst effect of ISFI. © 2012 Informa Healthcare USA, Inc.