The use of Nifedipine (NI), a dihydropyridine
calcium channel blocker, is limited due to its
poor aqueous solubility. However, NI loaded solid-lipid nanoparticles (NI-SLN)
are known to exhibit suitable pharmacokinetic properties and good
biocompatibility. The present investigation was designed to evaluate the
effects of NI-SLN on glucose homeostasis, lipid metabolism and liver function
in fructose-induced diabetic rats. NI-SLN was prepared by high pressure
homogenization technique followed by lyophilization with trehalose as
cryoprotectant. Diabetes was induced into rats by the administration of
fructose (10%) in drinking water for six weeks. After induction of diabetes,
rats were divided into four groups for the oral ingestion of NI, NI-SLN and/or
vehicles and their effects on blood glucose levels, oral glucose tolerance test
(OGTT), lipid profile, biochemical parameters, electrolytes and histopathology
were observed. Single dose administration and treatment with NI-SLN showed
significant glucose lowering efficacy in fructose-induced diabetic rats.
Although NI and NI-SLN did not alter the fasting blood glucose level in normal
rats, diabetic rats treated with NI-SLN resulted in significant reduction in
glucose level for 24 hr. In OGTT, NI-SLN exhibited significant
antihyperglycemic activity in both normal and diabetic rats. So, NI-SLN has
better glucose lowering efficacy than that of pure NI in diabetic rats. The
survival rates in rats among the treatment groups were 100%. Treatment with
NI-SLN significantly improved lipid profiles than NI alone and the effect was
dose-dependent. Administration of NI-SLN significantly reduced uric acid,
creatinine levels and maintained a good cationic balance. After two weeks of
NI-SLN treatment, hepatocytes regained their
normal architecture, and the beneficial effect could be correlated with the reduction of SGOT and total bilirubin levels.
Therefore, NI-SLN was found to be
useful for the enhancement of bioavailability and exhibited profound
antidiabetic activity in rats. The results of the study suggested that
NI-SLN exerted better improvement in glucose levels, lipid profiles and organ
protection than pure NI and might have some beneficial effects in the
management of diabetic patients.