In vivo and cytotoxicity evaluation of repaglinide-loaded binary solid lipid nanoparticles after oral administration to rats.

The purpose of this work was to develop prolonged release binary lipid matrix-based solid lipid nanoparticles (SLN) of repaglinide (RG) for oral intestinal delivery and to improve the bioavailability of RG. SLN were designed by using glycerol monostearate and tristearin as lipid core materials and Pluronic-F68 as stabilizer. SLN were characterised by their particle size, zeta potential, entrapment efficiency, solid-state studies, in vitro drug release, particle surface and storage stability at 30 °C/65% relative humidity for 3 months. Pharmacodynamic (PD) and pharmacokinetic (PK) studies were also performed in diabetes-induced rat. Moreover, an in vitro toxicity study was performed in rat macrophage cells to establish the safety of the prepared SLN. It was observed that binary lipid matrix-based SLN had better drug entrapment, desired release characteristics, spherical shape and maximum storage stability. Pharmacodynamic study indicated that RG delivered through binary SLN significantly reduces blood glucose, blood cholesterol and blood triglycerides level. The area under the curves after oral administration of optimised RG-SLN formulation and RG control were 113.36 ± 3.01 and 08.08 ± 1.98 h/(ng · mL), respectively. The relative bioavailability of RG was enhanced with optimised SLN formulation when compared with RG control. There was a direct correlation found between the plasma drug level (drug concentration) and the peak response (% blood glucose inhibition) in optimised RG-SLN batch. The in vitro toxicity study indicated that the SLN were well tolerated.

Rawat MK ，Jain A ，Singh S 《-》

Studies on binary lipid matrix based solid lipid nanoparticles of repaglinide: in vitro and in vivo evaluation.

The purpose of present study is to examine effect of binary lipid matrix (combination of lipids) on the entrapment and storage stability of repaglinide (RG) loaded solid lipid nanoparticles (SLN). Solid lipid nanoparticles were prepared by modified solvent injection method for oral delivery to improve the bioavailability of RG, an antidiabetic drug. The stearic acid and tristearin were used to form lipid core materials, and Pluronic-F68 was used as a stabilizer. Nanoparticles were characterized by evaluating their particle size, zeta potential, entrapment efficiency, drug loading, solid-state studies (differential scanning calorimetry, X-ray diffraction), in vitro drug release, particle surface (transmission electron microscopy analysis with electron diffraction pattern), stability study in gastrointestinal fluids (GIFs) and storage stability at 30 °C/65% RH for 3 months. The characterization of SLN suggested that binary lipid matrix based nanoparticles had better drug entrapment and loading, desired release characteristics, stable in GIFs and significantly higher storage stability compared with single lipid formulations. Pharmacodynamic (blood glucose, blood cholesterol, blood triglyceride levels) and pharmacokinetic (AUC, T(max), peak plasma concentrations, K, t(1/2), mean residence time and relative bioavailabilities) studies were performed for the selected formulations. These studies indicate that the formulation based on binary lipid matrix significantly improves the oral bioavailability of RG.

Rawat MK ，Jain A ，Singh S 《-》

Effect of lipid matrix on repaglinide-loaded solid lipid nanoparticles for oral delivery.

Rawat MK ，Jain A ，Mishra A ，Muthu MS ，Singh S ... -  《-》

Development and characterization of a novel lipohydrogel nanocarrier: repaglinide as a lipophilic model drug.

Solid lipid nanoparticles (SLNs) are highly susceptible to phagocytosis by reticuloendothelial system (RES). To overcome this problem, a novel hydrogel-coated SLNs structure was developed and evaluated in this study. Solid lipid nanoparticles surface was coated with chitosan, via electrostatic attraction with the negatively charged SLNs surface. The resulting polymer-coated SLNs then hosted an inorganic poly-anionic agent, tripolyphosphate, to form the final lipohydrogel structure. Compared with the bare SLNs, lipohydrogel nanoparticles (LHNs) showed a significant increase in size and zeta potential. The release profile showed lower burst release and lower release rate for LHNs compared with SLNs. LHNs nanoparticles released the model antidiabetic drug, repaglinide, in a more sustained manner with lower burst effect compared with the corresponding SLN structure. Cytotoxicity studies via cell culture and MTT assay revealed no bio-toxicity of the SLNs and LHNs. In addition, intravenous administration of repaglinide-loaded SLNs and LHNs in rats showed longer drug residence time in circulation for LHNs, a trend also evident for the blood glucose level-time profile. The particle size, zeta potential, FTIR and microscopy data demonstrated the formation of the supposed lipohydrogel nanoparticles. All these benefits of LHNs propose it as a promising candidate for controlled release of the drugs.

Ebrahimi HA ，Javadzadeh Y ，Hamidi M ，Barzegar Jalali M ... -  《-》

Development of repaglinide loaded solid lipid nanocarrier: selection of fabrication method.

Rawat MK ，Jain A ，Mishra A ，Muthu MS ，Singh S ... -  《-》