Intranasal repaglinide-solid lipid nanoparticles integrated in situ gel outperform conventional oral route in hypoglycemic activity

Abstract

Repaglinide (REP) loaded solid-lipid nanoparticles (SLNs) for intranasal administration is the subject of the current work aiming enhancement of diabetes pharmacotherapy. SLNs were prepared by applying 32 factorial-design using the hot-melt emulsion technique. Surfactant and lipid types were selected as the independent variables. The optimized formula composed of glyceryl monostearate and Poloxamer 188 was further integrated into gellan gum (GG 0.5%w/v) in situ gel for ease of administration. The optimized SLNs integrated into situ gel (SLNF1.ISG0.5) showed small particle size (96.34nm), high EE (80.57%), and outstanding sustained release of only 83.3% after 30h. ISG formula showed pseudo-plastic behavior, mucoadhesive property, and physical stablility. TEM showed spherical nanoparticles associated with the hydrogel matrix. In vivo pharmacodynamic study results in diabetic rats’ proved to be safe and succeeded to show superior hypoglycemic-activity for REP after nasal administration versus oral route manifested by higher 1.2-fold % maximum reduction, the 2.5-fold total decrease in blood glucose level with a significantly longer duration of action > 48h. Conclusively, the developed intranasal drug-loaded-SLNs integrated in-situ gel formula succeeded to achieve the maximum therapeutic outcome of repaglinide in dose reduction frequency for diabetes mellites treatment.