Solid lipid nanoparticles for delivery of andrographolide across the blood-brain barrier: in vitro and in vivo evaluation

• DOI: 10.1016/j.colsurfb.2017.10.062
• Publication Date: 2017-11-06T17:16:13Z
• Authors: Giulia Graverini; Vieri Piazzini; Elisa Landucci; Daniela Pantano; Pamela Nardiello; Fiorella Casamenti; Domenico E. Pelle...; Anna Rita Bilia; Maria Camilla Ber...
• Keywords: 0301 basic medicine; Cell Survival; Anti-Inflammatory Agents; Brain; Lipids; Cell Line; 3. Good health; Drug Liberation; 03 medical and health sciences; Drug Delivery Systems; Microscopy, Electron, Transmission; Blood-Brain Barrier; Andrographolide, stealth SLN, Stability, PAMPA assay; hCMEC/D3 cells; in vivo evaluation; Animals; Humans; Nanoparticles; Administration, Intravenous; Tissue Distribution; Diterpenes; Rats, Wistar

Andrographolide is a major diterpenoid of Andrographis paniculata and possesses several biological activities, including protection against oxidative stress mediated neurotoxicity, inflammation-mediated neurodegeneration, and cerebral ischemia. However, this molecule shows low bioavailability, poor water solubility, and high chemical and metabolic instability. The present study reports preparation of solid lipid nanoparticles (SLN) to deliver andrographolide (AG) into the brain. SLN were prepared using Compritol 888 ATO as solid lipid and Brij 78 as surfactant and applying emulsion/evaporation/solidifying method as preparative procedure. Nanoparticles have a spherical shape, small dimensions, and narrow size distribution. Encapsulation efficiency of AG-loaded SLN was found to be 92%. Nanoparticles showed excellent physical and chemical stability during storage at 4°C for one month. The lyophilized product was also stable at 25°C during the same period. SLN remained unchanged also in the presence of human serum albumin and plasma. In vitro release at pH 7.4 was also studied. The release of AG was prolonged and sustained when the compound was entrapped in SLN. The ability of SLN to cross the blood-brain barrier (BBB) was evaluated first in vitro by applying a permeation test with artificial membrane (parallel artificial membrane permeability assay, PAMPA) to predict passive and transcellular permeability through the BBB, and then by using hCMEC/D3 cells, a well-established in vitro BBB model. In vitro results proved that nanoparticles improved permeability of AG compared to free AG. Fluorescent nanoparticles were then prepared for in vivo tests in healthy rats. After intravenous administration, fluorescent SLN were detected in brain parenchyma outside the vascular bed, confirming their ability to overcome the BBB.