Ezetimibe-Loaded Nanostructured Lipid Carrier Based Formulation Ameliorates Hyperlipidaemia in an Experimental Model of High Fat Diet.
Yogeeta O AgrawalUmesh B MahajanVinit V AgnihotriMayur S NilangeHitendra S MahajanCharu SharmaShreesh Kumar OjhaChandragouda R PatilSameer N GoyalPublished in: Molecules (Basel, Switzerland) (2021)
Ezetimibe (EZE) possesses low aqueous solubility and poor bioavailability and in addition, its extensive hepatic metabolism supports the notion of developing a novel carrier system for EZE. Ezetimibe was encapsulated into nanostructured lipid carriers (EZE-NLCs) via a high pressure homogenization technique (HPH). A three factor, two level (23) full factorial design was employed to study the effect of amount of poloxamer 188 (X1), pressure of HPH (X2) and number of HPH cycle (X3) on dependent variables. Particle size, polydispersity index (PDI), % entrapment efficiency (%EE), zeta potential, drug content and in-vitro drug release were evaluated. The optimized formulation displays pragmatic inferences associated with particle size of 134.5 nm; polydispersity index (PDI) of 0.244 ± 0.03; zeta potential of -28.1 ± 0.3 mV; % EE of 91.32 ± 1.8% and % CDR at 24-h of 97.11%. No interaction was observed after X-ray diffraction (XRD) and differential scanning calorimetry (DSC) studies. EZE-NLCs (6 mg/kg/day p.o.) were evaluated in the high fat diet fed rats induced hyperlipidemia in comparison with EZE (10 mg/kg/day p.o.). Triglyceride, HDL-c, LDL-c and cholesterol were significantly normalized and histopathological evaluation showed normal structure and architecture of the hepatocytes. The results demonstrated the superiority of EZE-NLCs in regard to bioavailability enhancement, dose reduction and dose-dependent side effects.
Keyphrases
- high fat diet
- drug delivery
- drug release
- adipose tissue
- insulin resistance
- electron microscopy
- low density lipoprotein
- high resolution
- cancer therapy
- drug induced
- liver injury
- high glucose
- fatty acid
- photodynamic therapy
- type diabetes
- diabetic rats
- mouse model
- human health
- clinical trial
- computed tomography
- randomized controlled trial
- oxidative stress
- wound healing
- emergency department
- stress induced