title: In vivo and cytotoxicity evaluation of repaglinide-loaded binary solid lipid nanoparticles after oral administration to rats.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India. bitsmanoj@gmail.com
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Rawat
authors.forename: Achint
authors.initials: A
authors.lastname: Jain
authors.forename: Sanjay
authors.initials: S
authors.lastname: Singh
mesh_terms: D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D002219:Carbamates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D008055:Lipids / Q000737:chemistry*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D044367:Phase Transition; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties
chemical_list: D001786:Blood Glucose; D002219:Carbamates; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D008055:Lipids; D010880:Piperidines; C072379:repaglinide