Stability and Release Kinetics of an Advanced Gliclazide-Cholic Acid Formulation: The Use of Artificial-Cell Microencapsulation in Slow Release Targeted Oral Delivery of Antidiabetics

Introduction: In previous studies carried out in our laboratory, a bile acid (BA) formulation exerted a hypoglycaemic effect in a rat model of type-1 diabetes (T1D). When the antidiabetic drug gliclazide (G) was added to the bile acid, it augmented the hypoglycaemic effect. In a recent study, we designed a new formulation of gliclazide-cholic acid (G-CA), with good structural properties, excipient compatibility and exhibits pseudoplastic-thixotropic characteristics. The aim of this study is to test the slow release and pH-controlled properties of this new formulation. The aim is also to examine the effect of CA on G release kinetics at various pH values and different temperatures. Method: Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) and G-CA-SA (test) at a constant ratio (1:3:30), respectively. Microcapsules were examined for efficiency, size, release kinetics, stability and swelling studies at pH 1.5, pH 3, pH 7.4 and pH 7.8 and temperatures of 20 and 30 °C. Results: The new formulation is further optimised by the addition of CA. CA reduced microcapsule swelling of the microcapsules at pH 7.8 and pH 3 at 30 °C and pH 3 at 20 °C, and, even though microcapsule size remains similar after CA addition, percent G release was enhanced at high pH values (pH 7.4 and pH 7.8, p < 0.01). Conclusion: The new formulation exhibits colon-targeted delivery and the addition of CA prolonged G release suggesting its suitability for the sustained and targeted delivery of G and CA to the lower intestine

Diabetes and hypertension increase the placental and transcellular permeation of the lipophilic drug diazepam in pregnant women

Background: Previous studies carried out in our laboratories have demonstrated impaired drug permeation in diabetic animals. In this study the permeation of diazepam (after a single dose of 5 mg/day, administered intramuscularly) will be investigated in diabetic and hypertensive pregnant women.Methods: A total 75 pregnant women were divided into three groups: group 1 (healthy control, n = 31), group 2 (diabetic, n = 14) and group 3 (hypertensive, n = 30). Two sets of diazepam plasma concentrations were collected and measured (after the administration of the same dose of diazepam), before, during and after delivery. The first set of blood samples was taken from the mother (maternal venous plasma). The second set of samples was taken from the fetus (fetal umbilical venous and arterial plasma). In order to assess the effect of diabetes and hypertension on diazepam placental-permeation, the ratios of fetal to maternal blood concentrations were determined. Differences were considered statistically significant if p=0.05.Results: The diabetes and hypertension groups have 2-fold increase in the fetal umbilical-venous concentrations, compared to the maternal venous concentrations. Feto: maternal plasma-concentrations ratios were higher in diabetes (2.01 ± 1.10) and hypertension (2.26 ± 1.23) groups compared with control (1.30 ± 0.48) while, there was no difference in ratios between the diabetes and hypertension groups. Umbilical-cord arterial: venous ratios (within each group) were similar among all groups (control: 0.97 ± 0.32; hypertension: 1.08 ± 0.60 and diabetes: 1.02 ± 0.77).Conclusions: On line with our previous findings which demonstrate disturbed transcellular trafficking of lipophilic drugs in diabetes, this study shows significant increase in diazepam placental-permeation in diabetic and hypertensive pregnant women suggesting poor transcellular control of drug permeation and flux, and bigger exposure of the fetus to drug-placental transport

A comprehensive health effects assessment of the use of sanitizers and disinfectants during COVID-19 pandemic: a global survey

COVID-19 has affected all aspects of human life so far. From the outset of the pandemic, preventing the spread of COVID-19 through the observance of health protocols, especially the use of sanitizers and disinfectants was given more attention. Despite the effectiveness of disinfection chemicals in controlling and preventing COVID-19, there are critical concerns about their adverse effects on human health. This study aims to assess the health effects of sanitizers and disinfectants on a global scale. A total of 91,056 participants from 154 countries participated in this cross-sectional study. Information on the use of sanitizers and disinfectants and health was collected using an electronic questionnaire, which was translated into 26 languages via web-based platforms. The findings of this study suggest that detergents, alcohol-based substances, and chlorinated compounds emerged as the most prevalent chemical agents compared to other sanitizers and disinfectants examined. Most frequently reported health issues include skin effects and respiratory effects. The Chi-square test showed a significant association between chlorinated compounds (sodium hypochlorite and per-chlorine) with all possible health effects under investigation (p-value <0.001). Examination of risk factors based on multivariate logistic regression analysis showed that alcohols and alcohols-based materials were associated with skin effects (OR, 1.98; 95%CI, 1.87-2.09), per-chlorine was associated with eye effects (OR, 1.83; 95%CI, 1.74-1.93), and highly likely with itching and throat irritation (OR, 2.00; 95%CI, 1.90-2.11). Furthermore, formaldehyde was associated with a higher prevalence of neurological effects (OR, 2.17; 95%CI, 1.92-2.44). Furthermore, formaldehyde was associated with a higher prevalence of neurological effects (OR, 2.17; 95%CI, 1.92-2.44). The use of sodium hypochlorite and per-chlorine also had a high chance of having respiratory effects. The findings of the current study suggest that health authorities need to implement more awareness programs about the side effects of using sanitizers and disinfectants during viral epidemics especially when they are used or overused