Formulation Development of a Food-Graded Curcumin-Loaded Medium Chain Triglycerides-Encapsulated Kappa Carrageenan (CUR-MCT-KC) Gel Bead Based Oral Delivery Formulation.

In recent years, curcumin has been a major research endeavor in food and biopharmaceutical industries owing to its miscellaneous health benefits. There is an increasing amount of research ongoing in the development of an ideal curcumin delivery system to resolve its limitations and further enhance its solubility, bioavailability and bioactivity. The emergence of food-graded materials and natural polymers has elicited new research interests into enhanced pharmaceutical delivery due to their unique properties as delivery carriers. The current study is to develop a natural and food-graded drug carrier with food-derived MCT oil and a seaweed-extracted polymer called k-carrageenan for oral delivery of curcumin with improved solubility, high gastric resistance, and high encapsulation of curcumin. The application of k-carrageenan as a structuring agent that gelatinizes o/w emulsion is rarely reported and there is so far no MCT-KC system established for the delivery of hydrophobic/lipophilic molecules. This article reports the synthesis and a series of in vitro bio-physicochemical studies to examine the performance of CUR-MCT-KC as an oral delivery system. The solubility of CUR was increased significantly using MCT with a good encapsulation efficiency of 73.98 ± 1.57% and a loading capacity of 1.32 ± 0.03 mg CUR/mL MCT. CUR was successfully loaded in MCT-KC, which was confirmed using FTIR and SEM with good storage and thermal stability. Dissolution study indicated that the solubility of CUR was enhanced two-fold using heated MCT oil as compared to naked or unformulated CUR. In vitro release study revealed that encapsulated CUR was protected from premature burst under simulated gastric environment and released drastically in simulated intestinal condition. The CUR release was active at intestinal pH with the cumulative release of >90% CUR after 5 h incubation, which is the desired outcome for CUR absorption under human intestinal conditions. A similar release profile was also obtained when CUR was replaced with beta-carotene molecules. Hence, the reported findings demonstrate the potencies of MCT-KC as a promising delivery carrier for hydrophobic candidates such as CUR.

Mice lacking the ß2 adrenergic receptor have a unique genetic profile before and after focal brain ischaemia.

The role of the ß2AR (ß2 adrenergic receptor) after stroke is unclear as pharmacological manipulations of the ß2AR have produced contradictory results. We previously showed that mice deficient in the ß2AR (ß2KO) had smaller infarcts compared with WT (wild-type) mice (FVB) after MCAO (middle cerebral artery occlusion), a model of stroke. To elucidate mechanisms of this neuroprotection, we evaluated changes in gene expression using microarrays comparing differences before and after MCAO, and differences between genotypes. Genes associated with inflammation and cell deaths were enriched after MCAO in both genotypes, and we identified several genes not previously shown to increase following ischaemia (Ccl9, Gem and Prg4). In addition to networks that were similar between genotypes, one network with a central core of GPCR (G-protein-coupled receptor) and including biological functions such as carbohydrate metabolism, small molecule biochemistry and inflammation was identified in FVB mice but not in ß2KO mice. Analysis of differences between genotypes revealed 11 genes differentially expressed by genotype both before and after ischaemia. We demonstrate greater Glo1 protein levels and lower Pmaip/Noxa mRNA levels in ß2KO mice in both sham and MCAO conditions. As both genes are implicated in NF-κB (nuclear factor κB) signalling, we measured p65 activity and TNFα (tumour necrosis factor α) levels 24 h after MCAO. MCAO-induced p65 activation and post-ischaemic TNFα production were both greater in FVB compared with ß2KO mice. These results suggest that loss of ß2AR signalling results in a neuroprotective phenotype in part due to decreased NF-κB signalling, decreased inflammation and decreased apoptotic signalling in the brain.

Diabetes connect: an evaluation of patient adoption and engagement in a web-based remote glucose monitoring program.

BACKGROUND: We determine whether Diabetes Connect (DC), a Web-based diabetes self-management program, can help patients effectively manage their diabetes and improve clinical outcomes. METHODS: Diabetes Connect is a 12-month program that allows patients with type 2 diabetes mellitus to upload their blood glucose readings to a database, monitor trends, and share their data with their providers. To examine the impact of the program, we analyzed patient utilization and engagement data, clinical outcomes, as well as qualitative feedback from current and potential users through focus groups. RESULTS: We analyzed 75 out of 166 patients. Mean age was 61 years (range 27-87). Patients engaged in DC had an average hemoglobin A1c (HbA1c) change of 1.5%, while nonengaged patients had a HbA1c change of 0.4% (p = .05). Patients with the best outcomes (HbAlc decline of at least 0.8%) typically took less than 10 days to upload, while patients with the worst outcomes (a rise in HbAlc) took an average of 65 days to upload. Patients with more engaged providers had a better HbA1c change (1.39% versus 0.87%) for practices with an average of 74 versus 30 logins/providers. CONCLUSIONS: Patient engagement in the program has a positive impact on the outcomes of this collaborative Web-based diabetes self-management tool. Patients who engage early and remain active have better clinical outcomes than unengaged patients. Provider engagement, too, was found critical in engaging patients in DC.