Abstract
Aim: Guggul lipid, a lipophillic antihyperlipidemic moiety, undergoes extensive first-pass metabolism and has low bioavailability. In order to address this limitation, guggul lipid loaded chitosan nanoparticles (GNPs) were designed, optimized and processed by 3- factor 3- level Box- Behnken design (BBD).
 Methodology: A 3-factor 3-level BBD was employed to investigate combined influence of formulation variables on percent entrapment efficiency (EE) and percent drug release (DR) of GNPs prepared by ionic gelation method. The generated polynomial equation was validated and desirability function was utilized for optimization. Optimized GNPs were evaluated for physicochemical, morphological, release characteristics, solid state characterization and in-vitro cell line studies.
 Results: Amounts of chitosan, sodium tripolyphosphate and guggul were selected as independent variables had variably influenced EE and DR. Optimized GNPs were produced with an average size of 96.5 nm, electro kinetic potential of -15.4 mV, EE of 92.98% and DR of 95.12% in 24 h with sustained release. Physicochemical and in-vitro characterization revealed existence of guggul in amorphous form in GNPs without interaction and exhibited sustained release profile following first order with Higuchi kinetics. GNPs possessed lipase inhibition activity with IC50 value of 14.72 µg/ml and better viability against various cell lines with CTC50 values (256.24 to 321.27 µg/ml).
 Conclusions: Design and optimization of GNPs by BBD proved to be an effective and promising approach. High entrapment of guggul followed controlled release were the outcomes of GNPs prepared by ionic gelation with improved cell viability.
Highlights
Hyperlipidaemia is a heterogeneous disorder characterized by increased flux of free fatty acids raised triglycerides (TGs), low-density lipoprotein-cholesterol (LDL) and apolipoprotein B levels
The non-linear quadratic model generated by the BoxBehnken design (BBD) was: Compatibility studies for guggul, chitosan, sodium tripoly phosphate (TPP) and guggul lipid loaded chitosan nanoparticles (GNPs) were studied by Fourier Transform Infrared (FTIR) spectroscopy (Shimadzu 8300E)
The polynomial equation showing the effect of independent variables on drug release (DR) was as followed: Stability studies of optimized GNPs were carried out at room temperature (25±2°C), refrigerated condition (4±1°C) and accelerated condition
Summary
Hyperlipidaemia is a heterogeneous disorder characterized by increased flux of free fatty acids raised triglycerides (TGs), low-density lipoprotein-cholesterol (LDL) and apolipoprotein B (apoB) levels. Reduced plasma high-density lipoprotein (HDL) cholesterol is due to metabolic effects or dietary and lifestyle habits [1]. Hyperlipidemia, in turn, may lead to diabetes mellitus, fatty liver, cerebral infarction, hemiplegia and various cardiovascular disorders (CVDs) that accounts for one third of total deaths worldwide by 2020 [3,4,5]. Several synthetic moieties such as statins, fibrates, bile acid sequesterants, nicotinic acid derivatives, cholesterol absorption inhibitors and lipase inhibitors are prescribed to treat hyperlipidemia widely. The therapeutic efficacy of some of the above agents is limited by serious side effects viz., myopathy, rhabdomyolysis, hepatic toxicity, cardiomyopathy, kidney damage, bloating, flatulence, skin rashes, gallstones, abdominal pain, oily spots, diarrhoea and even death
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