Objective: The aim of this study was to formulate and optimize solid lipid nanoparticles (SLNs) for the enhancement of solubility and bioavailability of the poorly aqueous soluble drug rosuvastatin calcium.Methods: SLNs were prepared by slight modification of solvent emulsification-diffusion technique and analyzed for particle size, zeta potential, drug entrapment efficiency, in vitro drug release, stability, and pharmacokinetic studies. Rosuvastatin calcium SLNs were formulated using stearic acid as main lipid, poloxamer 407 as surfactant, and Tween 80 as cosurfactant.Results: All parameters were found to be in an acceptable range. Optimized formulation OR2 SLNs have shown mean particle size 115.49±2.97 nm with polydispersity index value of 0.456, zeta potential - 18.40 mV, 60.34% drug loading, and 97.16% drug entrapment efficiency. In vitro drug release was found to be 88.70±3.59% after 12 h with sustained release and was fitted with Higuchi model with a very high correlation coefficient (R2=0.9905). Transmission electron microscopy confirms that the SLNs of selected optimized formulation are circular in shape. Differential scanning calorimetry and X-ray diffraction confirm the formation of amorphous product. 1H nuclear magnetic resonance studies confirm the intermolecular hydrogen bonding between drug and lipid. Pharmacokinetic studies showed an optimized formulation OR2 SLNs enhanced bioavailability with 4.44-fold as compare to plain drug suspension. Optimized formulation OR2 SLNs have shown good stability at 25±2°C and 60±5°C relative humidity for 180 days.Conclusion: Thus, the current study can be useful for the successful development of optimized SLNs and able to enhance the bioavailability of poorly soluble drug rosuvastatin calcium.

: The aim of the present study was to review the streptozotocin-nicotinamide (STZ-NA) diabetes model. Type 2 diabetes is more prevalent (90-95%) in adults than type 1. Experimentally-induced diabetes models may be established by chemicals, viral agents, insulin antibodies, surgery, etc. The most advisable and prompt method to induce diabetes is using chemicals, and STZ and alloxan are widely used chemicals. STZ has proven to be a better diabetogenic agent than alloxan because alloxan has many drawbacks, as it induces only type 1 diabetes, has a high mortality rate in rats, and causes ketosis in animals. Moreover, it has lesser selectivity towards β-cells, and the diabetes-induced is reversible. STZ can be used to induce both type 1 and type 2 diabetes. It is noted that the genotoxic behavior of STZ in animals is accomplished through a reduction of nicotinamide adenine dinucleotide (NAD+) in pancreatic β-cells via the GLUT2 (Glucose transporter 2), which can cause cellular damage by DNA (Deoxyribonucleic acid) strand breaks that lead to cell death. NA is a biochemical precursor of NAD+, and it is a poly-ADP-ribose-polymerase-1 (PARP-1) inhibitor. NAD+ is an important redox reaction co-enzyme for the production of adenosine triphosphate (ATP) and many other metabolic pathways. Extreme DNA damage contributes to the over-activation of PARP-1, loss of cellular resources, and necrotic cells death. Some studies have expressed that NA can protect pancreatic β-cells against the severe cytotoxicity of STZ. The review concluded that the STZ-NA model is dependent on the competency of NA to attain partial protection against the β-cytotoxic essence of STZ to induce type-2 diabetes.

No abstract

No abstract

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia resulting long-term secondary complication. Aldose reductase, the rate-limiting enzyme of the polyol pathway, plays a key role in the treatment of diabetic complications. Appropriately, inhibition of this enzyme is emerging as a major therapeutic strategy for the pathogenesis of secondary complication. In this study, we describe a series of 5 aryl benzylidene -thiazolidine, 4-dione derivatives, F3 synthesized as aldose reductase inhibitors. Besides inhibiting efficiently the target enzyme, F4 and F5 showed additional AR inhibitory as well as hypoglycaemic activity (146.15 and 175.20 mg/dl ) thus emerging as novel dual acting compounds. The bezylidene derivative F3, the most promising of the whole series, showed a well-balanced, consisting of ALR2 inhibitory efficacy (83.00% at 10µg/mL), similarly, F3 have lower blood glucose level in the range of 131.11 mg/dl at 15 mg/kg body weight. This compound show robust in vitro and in vivo efficacy, and could be considered as promising dual target antidiabetic drug candidates. Keywords: Diabetes mellitus, hyperglycemia, Aldose reductase inhibitors