Polysaccharide Encrusted Multilayered Nano-Colloidal System of Andrographolide for Improved Hepatoprotection.

Abstract

Andrographolide (AP), a phytoconstituent of Andrographis paniculata is reported as a potent hepatoprotective agent. However, utility of this molecule is restricted due to its low aqueous solubility, gastric instability and hence low bioavailability. It was aimed to formulate and characterize AP-loaded, natural biopolymer stabilized, multilayered nano-hydrocolloid delivery system. Nanoemulsion (NE) was formulated using layer-by-layer (LbL) technology via electrostatic deposition of chitosan over alginate encrusted o/w NE by ultra-sonication. Improved transparency and stability of NE were observed with increasing sonication time. Best stability was obtained after 20min sonication and particle size of the multilayered NE was measured in the range of 90.8-167.8nm. Transmission electron microscopy confirmed the progressive layering of nanosized NE. Higher magnitude of zeta potential (i.e., 22.9 to 31.01mV) confirmed higher stability and coating of alginate layer over NE surface for the period of 3months. NE showed strategic release pattern when assessed in vitro in various simulated biological fluids of GIT in timed pattern. Multilayered NE showed significant modulation in liver function test (ALT, ALP, AST, TBIL, DBIL, and liver glycogen) and serum cytokines (TNF-α, IL-6, IL-10, and IL-β) when assessed in vivo in galactosamine-lipopolysaccharide intoxicatedmice. In conclusion, the andrographolide engrained multi-layered NE enhanced the solubility, stability and henceforth assured the increased availability in simulated biological fluids. The in vivo study exhibited the significantly improved hepatoprotection by andrographolide when delivered in stable multi-layered NE carrier systems.