Expanding arsenal against diabetes mellitus through nanoformulations loaded with glimepiride and simvastatin: A comparative study

Narendra Kumar Pandey,Bimlesh Kumar,Sukriti Vishwas,Dinesh Kumar Chellappan,Gaurav Gupta,Saurabh Kumar Jha,Monica Gulati,Ankur Sharma,Rubiya Khursheed,Saurabh Gupta,Niraj Kumar Jha,Parteek Prasher,Piyush Kumar Gupta,Sachin Kumar Singh,Kamal Dua,Harish Dureja

doi:10.1007/s11356-022-19371-z

Abstract

Type 2 diabetes mellitus is one of the most common and life-threatening diseases found across the globe. It occurs due to insulin resistance (IR). Major causes of IR include obesity, sedentary life style and hyperlipidemia. Glimepiride (GLM) is one of the most common oral sulphonyl ureas that is being used to treat diabetes and Simvastatin (SIM) is one of the most common statins that is used to treat hyperlipidaemia. However, both the drugs suffer from dissolution rate limited oral bioavailability. Hence, the aim of present study was to develop two different nanoformulations viz. nanosuspension and self-nanoemulsifying drug delivery systems (SNEDDS) and evaluate their potential in treating type 2 diabetes mellitus on streptozotocin (STZ) induced rats. In the present study two such drugs, GLM and SIM were co-formulated into nanosuspension (NS) as well as self-nanoemulsifying drug delivery systems (L-SNEDDS). Both formulations were spray dried for solidification and evaluated for their antidiabetic potential against high fat diet and streptozotocin induced rat model. The study showed significant (p < 0.05) decrease in lipid/cholesterol and blood glucose levels and significant increase in antioxidant levels in the rats treated with NS and SNEDDS containing the drugs alone as well as their combination as compared to their unprocessed forms. However, the efficacy was more prominent in case of combination possibly due to dual benefits i.e., decrease in IR due to statin and control of blood glucose level. Among NS and SNEDDS, NS was found more efficacious than that of the SNEDDS possibly due to higher enhancement of oral bioavailability in case of NS.

Highlights

Diabetes mellitus (DM) is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to insulin that is produced
The pharmacokinetic studies carried on rats revealed that the total plasma concentration of both the drugs in self-nanoemulsifying drug delivery system (SNEDDS) and spray dried nanosuspension powder (SP-NS) were significantly (P < 0.05) higher than that of their unprocessed form
About 6.69- and 4.22-folds increase in the area under the curves (AUCs) of GLM present in nanosuspensions and SNEDDS and about 1.76- and 2.68-folds increase AUCs of SIM present in nanosuspensions and SNEDDS were reported as compared to their unprocessed forms

Summary

Introduction

Diabetes mellitus (DM) is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin (type 1), or because cells do not respond to insulin (insulin resistance) that is produced (type 2). Glimepiride (GLM) belongs to the sulfonylureas class of antidiabetic drugs It reduces blood glucose level by stimulation of beta cells of pancreas for releasing insulin (Basit et al 2012, Rajesh et al 2018). SIM and GLM are highly lipophilic and possess dissolution rate limited oral bioavailability (Rajesh et al 2018, Sharma et al 2018). Both the drugs were coformulated into nanosuspension (NS) and self-nanoemulsifying drug delivery system (SNEDDS) and their impact on enhancing the therapeutic efficacy of GLM and SIM in treating diabetes was investigated using high fat and streptozotocin (STZ) induced rat model

Methods

Results

Conclusion