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

Autor: Anna Rita Bilia, Maria Camilla Bergonzi, Elisa Landucci, Vieri Piazzini, Giulia Graverini, Daniela Pantano, Pamela Nardiello, Domenico E. Pellegrini-Giampietro, Fiorella Casamenti
Rok vydání: 2018
Předmět:
Cell Survival
Andrographolide
Anti-Inflammatory Agents
Synthetic membrane
02 engineering and technology
Pharmacology
030226 pharmacology & pharmacy
Cell Line
03 medical and health sciences
chemistry.chemical_compound
Drug Delivery Systems
0302 clinical medicine
Colloid and Surface Chemistry
Microscopy
Electron
Transmission
Pulmonary surfactant
In vivo
Solid lipid nanoparticle
medicine
Animals
Humans
Tissue Distribution
Rats
Wistar
Physical and Theoretical Chemistry
Brain
Surfaces and Interfaces
General Medicine
Permeation
021001 nanoscience & nanotechnology
Human serum albumin
Lipids
Bioavailability
Drug Liberation
chemistry
Blood-Brain Barrier
Andrographolide
stealth SLN
Stability
PAMPA assay
hCMEC/D3 cells
in vivo evaluation
Biophysics
Nanoparticles
Administration
Intravenous
Diterpenes
0210 nano-technology
Biotechnology
medicine.drug
Zdroj: Colloids and Surfaces B: Biointerfaces. 161:302-313
ISSN: 0927-7765
DOI: 10.1016/j.colsurfb.2017.10.062
Popis: 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.
Databáze: OpenAIRE
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