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Jitkasem Meewan,1 Sukrut Somani,1 Jamal Almowalad,1 Partha Laskar,1 Margaret Mullin,2 Graeme MacKenzie,1 Swapnil Khadke,1 Yvonne Perrie,1 Christine Dufès1 1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK; 2Glasgow Imaging Facility, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UKCorrespondence: Christine Dufès, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK, Tel +44 1415483796, Fax +44 1415522562, Email C.Dufes@strath.ac.ukBackground: The manufacture of nanoparticles using manual methods is hampered by its challenging scale-up and poor reproducibility. To overcome this issue, the production of zein nanoparticles entrapping a lipophilic drug model, coumarin-6, by using a microfluidic system was assessed in this study. The influence of PEG density and chain length on zein nanoparticle characteristics, as well as their uptake efficacy in melanoma cancer cells, was also evaluated.Methods: Zein nanoparticles were prepared by both manual and microfluidic approaches to allow comparison between the two processes. PEGylated zein nanoparticles with various PEG densities and chain lengths were produced by nanoprecipitation and characterized. Their cellular uptake was evaluated on B16F10 melanoma cancer cells in vitro.Results: Zein nanoparticles have successfully been produced by both manual and microfluidic approaches. Parameters such as total flow rate and flow rate ratio of the aqueous and organic phases in microfluidic process, as well as the method preparation and aqueous to organic phase volume ratio during nanoprecipitation, have been shown to strongly influence the characteristics of the resulting nanoparticles. Continuous microfluidics led to the production of nanoparticles with low yield and drug entrapment, unlike nanoprecipitation, which resulted in zein nanoparticles with an appropriate size and an optimal drug entrapment efficiency of 64%. The surface modification of the nanoparticles produced by nanoprecipitation, with lower PEG density and shorter PEG chain length made mPEG5K-zein (0.5:1) the most favorable formulation in our study, resulting in enhanced stability and higher coumarin-6 uptake by melanoma cancer cells.Conclusion: mPEG5K-zein (0.5:1) nanoparticles prepared by nanoprecipitation were the most promising formulation in our study, exhibiting increased stability and enhancing coumarin-6 uptake by melanoma cancer cells.Graphical Abstract: Keywords: zein nanoparticles, microfluidics, nanoprecipitation, poly(ethylene glycol), cellular uptake

Dyslipidemia is a significant morbidity associated with diabetes and cardiovascular disorders. The present study was undertaken to assess the lipid profile of type 2 diabetic and age-gender matched healthy subjects and its association, if any, with fasting plasma glucose. Clinically diagnosed diabetic subjects were recruited for the study. The fasting plasma glucose and lipid profiles were analyzed for 99 diabetic and 101 healthy volunteers. The blood samples were analyzed for fasting plasma glucose, total cholesterol, triglycerides, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol and very low density lipoprotein-cholesterol. Correlation analysis of lipid profile with fasting plasma glucose and calculation of risk ratio was done. The levels of high density lipoprotein-cholesterol and low density lipoprotein-cholesterol were found to be significantly low in diabetics and subjects with lower low density lipoprotein-cholesterol were on statins. Inspite of lower lipid values, the risk ratio for diabetics was significantly higher. The correlation analysis indicated significant difference in relationship between fasting plasma glucose, lipid parameters and risk ratios in the two groups. Diabetics with lower high density lipoprotein-cholesterol and higher total cholesterol present with a higher risk ratio pointing to need of non-statin high density lipoprotein-raising medications decreasing their predisposition to cardiovascular disorders. The study highlights the altered pattern of correlation of lipid profile with fasting plasma glucose in diabetics and their increased risk of cardiovascular disorders. The dyslipidemia in the form of triglyceridemia and significantly low high density lipoprotein-cholesterol in diabetics point towards the need of non-statin high density lipoprotein-raising medications. [ABSTRACT FROM AUTHOR]

Objective: The present study analyzed the effects of antidiabetic drugs on antioxidant enzymes and liver function test (LFT) markers and their association with homeostatic model assessment of insulin resistance (HOMA-IR) in type 2 diabetic subjects. Methods: We assessed healthy and diabetic subjects (100 each). Diabetic subjects were divided based on treatment with only metformin, metformin in combination with other antidiabetic drugs and insulin in combination with other antidiabetic drugs. LFT markers, antioxidant status and HOMA-IR were assessed in the subjects. Results: Superoxide dismutase activity was higher (p < 0.01) while catalase activity was lower (p < 0.01) in the diabetic subjects as compared to controls. Serum glutamate-pyruvate transaminase (SGPT) (p < 0.01) and bilirubin (p < 0.05) levels were higher in diabetic male subjects while urea (p < 0.05) levels were lower and SGPT (p < 0.01) levels were higher in diabetic female subjects. In male subjects consuming only metformin, a positive association between HOMA-IR and insulin (p < 0.05) was seen. A positive association between HOMA-IR and glucose (p < 0.01), insulin (p < 0.01), SOD (p < 0.01) and SGPT (p < 0.05) was seen in males receiving metformin with other drugs. Interestingly, the female subjects on metformin displayed a positive association between HOMA-IR and insulin (p < 0.05) only. A positive association of HOMA-IR with glucose (p < 0.01) and insulin (p < 0.05) was seen in females on metformin in combination with other anti-diabetic drugs. Conclusion: The alterations in the antioxidant enzyme activities and liver function tests are dependent upon the gender and glycemic status of subjects while the variations in correlations of HOMA-IR with antioxidant enzymes, liver function tests and inflammatory markers are dependent on type of treatments. [ABSTRACT FROM AUTHOR]