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.     

Risk Factors for Coronary Artery Disease in Indians

Background

A case control study was carried out to study the emerging risk factors for coronary artery disease in Indians. Methods: The diagnosis of coronary artery disease was based on correlation of clinical, biochemical, electrocardiography, echocardiography, treadmill testing and coronary arteriography findings. The study comprised 100 cases of coronary artery disease (acute coronary syndrome and chronic coronary artery disease) and 100 controls in two tertiary care service hospitals. The subjects were evaluated for total plasma homocysteine, insulin, C-reactive protein (CRP), lipoprotein fibrinogen and anti-chlamydial anti-bodies.

Result

Male to female ratio was 10:1 in study group with similar predominance of males in controls. Mean age of the cases was 47 years (range 25-59 years) and that of controls was 43 years (range 23-56 years). 64% cases had acute coronary syndrome and 34% had chronic coronary artery disease. In the coronary artery disease population, 76% cases had hyperhomocyteinemia, 9% hyperinsulinaemia, 11% abnormal CRP values, 23% abnormal lipoprotein (a) levels, 40% IgG anti-chlamydial anti-bodies and only 11% had Ig M anti-chlamydial antibodies. In the control population, 72% had hyperhomocystinaemia and 6% hyperinsulinaemia while 23% and 9% controls had IgG and IgM anti chlamydial antibodies respectively. In control group 19% cases had abnormal lipoprotein(a) levels and only 2% had abnormal C reactive protein values. Significant correlation of CAD was seen with CRP values and Ig G anti-chlamydial antibodies. Both the study group and controls had higher homocysteine levels than that observed in some Indian and Western studies.

Conclusion

High C reactive protein levels and Ig G anti-chlamydial antibodies are associated with coronary artery disease in Indians. Insulin, lipoprotein A, fibrinogen, lgM anti-chlamydial antibodies and higher levels of total plasma homocysteine have no significant association with coronary artery disease.Key Words: Emerging risk factors, Coronary artery disease     

Fanconi anemia genes act to suppress a cross-linker-inducible p53- independent apoptosis pathway in lymphoblastoid cell lines

Hypersensitivity to cross-linking agents such as mitomycin C (MMC) is characteristic of cells from patients suffering from the inherited bone marrow failure syndrome. Fanconi anemia (FA). Here, we link MMC hypersensitivity of Epstein-Barr virus (EBV)-immortalized FA lymphoblasts to a high susceptibility for apoptosis and p53 activation. In MMC-treated FA cells belonging to complementation group C (FA-C), apoptosis followed cell cycle arrest in the G2 phase. In stably transfected FA-C cells, plasmid-driven expression of the wild-type cytoplasmic FAC protein relieved MMC-dependent G2 arrest and suppressed p53 activation. However, in both FA and non-FA lymphoblasts, p53 seemed not to be instrumental in the induction of MMC-dependent apoptosis, since overexpression of a dominant-negative p53 mutant failed to affect cell survival. In addition, no differences in the level of Bcl-2 expression, an inhibitor of apoptosis, were detected between FA and non- FA cells either in the absence or presence of MMC. Our findings suggest that FAC and the other putative FA gene products may function in a yet to be identified p53-independent apoptosis pathway.     

Progression of joint damage in early active severe rheumatoid arthritis during 18 months of treatment: comparison of low-dose cyclosporin and parenteral gold

OBJECTIVE: This study compared the progression of joint damage in patients with early active severe rheumatoid arthritis (RA) treated with cyclosporin or parenteral gold. METHODS: In this open, randomized, multicentre study with a blinded radiological endpoint, 375 patients who had suffered from active severe RA for <3 yr were randomized to be treated for 18 months with low-dose cyclosporin or parenteral gold. The groups were stratified with regard to corticosteroid use. Primary efficacy variables were numbers of erosions, erosion score and the Larsen-Dale joint damage score. RESULTS: Joint damage progressed at similar rates in both treatment arms. In both groups, patients receiving corticosteroids had less X-ray progression. Rheumatoid factor positivity, high swollen joint count, high erythrocyte sedimentation rate and pre-existing X-ray abnormalities predicted progression of joint damage. Although numbers of serious adverse events were similar, more gold patients (n = 65) than cyclosporin patients (n = 45) withdrew from study medication because of adverse events. CONCLUSION: Cyclosporin was comparable to parenteral gold in retarding progression of joint damage and was better tolerated in terms of adherence to therapy. The open label design should be kept in mind when assessing this difference.      

Growth Patterns in Small for Gestational Age Babies and Correlation with Insulin-like Growth Factor-1 Levels

Objective

Correlation of catch-up growth and Insulin-like Growth Factor -1 levels (IGF-I) in SGA babies.

Methods

50 Full-term Small for Gestational Age children aged 12–18 months were analyzed for Catch-up growth (gain in weight and/or length, Standard Deviation Score/SDS >0.67). IGF-1 was measured after post-glucose load using ELISA method and correlated with catch-up growth.

Results

Mean (SD) birthweight and length were 2.1 (0.3) Kg and 44.4 (3.1) cm, respectively. At enrollment, mean (SD) age, weight and length were 15.0 (2.1) months, 7.7 (1.3) Kg, and 72.9 (5.6) cm, respectively. Catch-up growth was noted in 60% children. IGF-1 levels were significantly higher in children showing catch-up growth (56.6 (63.2) ng/mL) compared to those not having catch up growth (8.7 (8.3) ng/mL). IGF-1 was positively correlated with both weight and length catch-up.

Conclusion

Majority of Small for Gestational Age showed catch-up growth by 18 months, which had good correlation with IGF-1 levels.

     

不同胰岛素促泌剂单药治疗对2型糖尿病患者死亡率和心血管风险的影响

研究纳入丹麦1997～2006年间107806例起始胰岛素促泌剂或二甲双胍单药治疗的2型糖尿病患者(年龄>20岁,没有使用过胰岛素单药和联合治疗)其中9607例患者既往存在心肌梗死史.随访时间3.3年,每3个月为一个区间,收集不同胰岛素促泌剂或二甲双胍的处方,如果某区间无处方量则以之前最多3个处方量的区间 作为参考.