Preparation of nanoparticle and nanoemulsion formulations containing repaglinide and determination of pharmacokinetic parameters in rats.

Repaglinide (RPG) belongs to the class of drugs known as meglitinides and is used for improving and maintaining glycemic control in the treatment of patients with Type 2 diabetes. RPG is a Class II drug (BCS) because of its high permeability and low water solubility. It also undergoes hepatic first-pass metabolism. The oral bioavailability of RPG is low (about 56 %) due to these drawbacks. Our aim in this study is to prepare two different nano-sized drug carrier systems containing RPG (nanoparticle: RPG-PLGA-Zein-NPs or nanoemulsion: RPG-NE) and to carry out a pharmacokinetic study for these formulations. We prepared NPs using PLGA and Zein. In addition, a single NE formulation was developed using Tween 80 and Pluronic F68 as surfactants and Labrasol as co-surfactant. The droplet size values of the blank-NE and RPG-NE formulations were found to be less than 120 nm. The mean particle sizes of blank-Zein-PLGA-NPs and RPG-Zein-PLGA-NPs were less than 260 nm. The Cmax and tmax values of RPG-Zein-PLGA-NPs and RPG-NE (523 ± 65 ng/mL and 770 ± 91 ng/mL; 1.41 ± 0.46 h and 1.61 ± 0.37 h, respectively) were meaningfully higher than those of free RPG (280 ± 33 ng/mL; 0.72 ± 0.28 h) (p < 0.05). The AUC0-∞ values calculated for RPG-Zein-PLGA-NPs and RPG-NE were approximately 4.04 and 5.05 times higher than that calculated for free RPG. These nanosized drug delivery systems were useful in increasing the oral bioavailability of RPG. Moreover, the NE formulation was more effective than the NP formulation in improving the oral bioavailability of RPG (p < 0.05).

Assessment of Pharmacokinetic Parameters of Daidzein-Containing Nanosuspension and Nanoemulsion Formulations After Oral Administration to Rats.

BACKGROUND AND OBJECTIVES: Daidzein has several biological effects such as antioxidation, anti-inflammation, chemoprevention, and anticancer effects. The aim of this study was to evaluate the impact of nano-formulations (nanoemulsion-NE and nanosuspension-NS) prepared to increase the oral bioavailability of daidzein, a poorly water-soluble isoflavone, on the pharmacokinetic parameters of daidzein in rats. METHODS: A high-performance liquid chromatography-ultraviolet (HPLC-UV) method was successfully developed for daidzein analysis in rat plasma. The pharmacokinetics studies of the nano-sized formulations, compared to coarse daidzein suspension, were carried out in the rats by a single oral dose at 10 mg/kg (n = 6/group). Area under the plasma concentration-time curve from time zero to extrapolation to time infinity (AUC0-∞), maximum plasma concentration (Cmax), time to reach maximum plasma concentration (tmax), and elimination half life (t1/2) values for coarse daidzein suspension, daidzein-NS, and daidzein-NE were estimated by a non-compartmental analysis. RESULTS: The AUC values of daidzein-NE and daidzein-NS were approximately 2.62 and 2.65 times higher than that of coarse daidzein suspension, respectively (p < 0.05). Relative bioavailability (Frel) (%) values of daidzein following oral administration of nanosuspension or nanoemulsion formulations were about 265.6% and 262.3%, respectively. CONCLUSION: It revealed that nanoscale size is an important factor to overcome any dissolution rate barriers to oral bioavailability of the low water-soluble compound. Nanoemulsion and nanosuspension formulations are beneficial dosage forms to increase the oral bioavailability of Biopharmaceutical Classification System (BCS) Class II and Class IV compounds.

Distribution of Aquaporin-4 channels in hippocampus and prefrontal cortex in mk-801-treated balb/c mice.

Functional disorders of the glymphatic system and Aquaporin-4 (AQP-4) channels take part in the pathophysiology of neurodegenerative disease. The aim of this study was to describe the distribution of AQP-4 channels in the prefrontal cortex and hippocampus in a mouse model of NMDA receptor blocking agent-induced schizophrenia-like behavior model. NMDA receptor antagonist MK-801 was used to produce the experimental schizophrenia model. MK-801 injections were administered for eleven days to Balb/c mice intraperitoneally. Beginning from the sixth day of injection, the spatial learning and memory of the mice were tested by the Morris water maze (MWM) task. A group of mice was injected with MK-801 for ten days without the MWM task. Hippocampus and prefrontal specimens were collected from this group. Tissue samples were stained immunohistochemically and AQP-4 channels were examined by electron microscope. Time to find the platform was significantly longer at MK-801 injected group than the control group at the MWM task. Also, time spent at the target quadrant by the MK-801 group was shorter compared to the control group. AQP-4 expression increased significantly at MK-801 group glial cells, neuronal perikaryon, perineuronal and pericapillary spaces. In the MK-801 group, there was remarkable damage in neurons and glial cells. Increased AQP-4 channel expression and neurodegeneration at the MK-801 group induced with schizophrenia-like behavior model. MK-801 induced NMDA receptor blockade causes a decline in cognitive and memory functions. Increased AQP-4 expression at the prefrontal cortex and hippocampus to elicit and transport products of synaptic neurotransmitters and end metabolites is suggested.