Formulation and optimization of lornoxicam-loaded bilosomes using 23 full factorial design for the management of osteoarthritis in rats: Modulation of MAPK/Erk1 signaling pathway

Abstract

The objective of this study was to formulate and evaluate Lornoxicam (LOX) loaded bilosomes for effective treatment of osteoarthrotis. Lornoxicam bilosomes were formulated using thin film hydration method. A 23 full factorial design was employed to evaluate the effect of different formulation variables. Three independent variables were studied; bile salt type (X1), drug amount (X2) and lipid: bile salt ratio (X3). The dependent responses were; entrapment efficiency (Y1: EE %), vesicles size (Y2: VS) and zeta potential (Y3: ZP). Design Expert® software was utilized to statistically optimize formulation variables. The vesicles revealed high LOX encapsulation efficiency ranging from 56.01 ± 3.26 to 82.70 ± 1.80% whereas vesicle size ranged from 94.04 ± 6.5 to 292.5 ± 5.3 nm. High negative zeta potential values indicated good stability of the prepared formulations. The optimized vesicles exhibited spherical morphology under transmission electron microscopy (TEM). LOX release from bilosomes was biphasic and the release pattern followed Higuchi's model. In-vivo studies confirmed the efficiency of LOX bilosomes in treatment of osteoarthritis by improving locomotor activity and coordination, inhibiting pro-inflammatory cytokines; IL-6, and NF-κβ as well as blocking mitogen-activated protein kinases (MAPKs)/extracellular signal-regulated kinase (ERK) pathway. Moreover, in-vivo histopathological studies of knee joint tissues treated with LOX bilosomal formulations showed a reduction in inflammatory cells infiltration with average synovial lining and average articular cartilage. The results revealed that the developed LOX bilosomes could be a promising drug delivery system to be used in the treatment of osteoarthritis.