Design of Guggul Lipid Loaded Chitosan Nanoparticles Using Box-Behnken Design – An Evaluation Study

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.