Planta Medica International Open 2017; 4(S 01): S1-S202
DOI: 10.1055/s-0037-1608383
Poster Session
Georg Thieme Verlag KG Stuttgart · New York

BRAIN-TARGETED DELIVERY OF ANDROGRAPHOLIDE USING SOLID LIPID NANOPARTICLES: IN VITRO AND IN VIVO EVALUATION

G Graverini
1   Department of Chemistry, University of Florence, Sesto Fiorentino, Florence, Italy
,
V Piazzini
1   Department of Chemistry, University of Florence, Sesto Fiorentino, Florence, Italy
,
E Landucci
2   Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy
,
D Pantano
3   Department of Neuroscience, Psychology, Drug Research and Child Health Division of Pharmacology and Toxicology, University of Florence, Florence, Italy
,
P Nardiello
3   Department of Neuroscience, Psychology, Drug Research and Child Health Division of Pharmacology and Toxicology, University of Florence, Florence, Italy
,
F Casamenti
3   Department of Neuroscience, Psychology, Drug Research and Child Health Division of Pharmacology and Toxicology, University of Florence, Florence, Italy
,
D Pellegrini-Giampietro
2   Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy
,
R Bilia Anna
1   Department of Chemistry, University of Florence, Sesto Fiorentino, Florence, Italy
,
C Bergonzi Maria
1   Department of Chemistry, University of Florence, Sesto Fiorentino, Florence, Italy
› Author Affiliations
Further Information

Publication History

Publication Date:
24 October 2017 (online)

 

Andrographolide (AG) is the major diterpenoid of Andrographis paniculata (Burm. f.) Wall. ex Nees (Acanthaceae) and have been reported to exhibit a wide spectrum of activities, including protection against oxidative stress, inflammation-mediated neurodegeneration and against cerebral ischemia [1]. However, AG shows low bioavailability and high chemical and metabolic instability. Moreover, up to now, there is no experimental evidence of AG crossing the blood brain barrier (BBB) in sufficient amount to achieve therapeutically relevant concentrations in the brain. To overcome these drawbacks the aim of this study was the preparation of solid lipid nanoparticles (SLNs) for brain delivery of AG. AG-SLNs have been developed using Compritol 888 ATO as solid lipid and Brij 78 as surfactant by emulsion/evaporation/solidifying method [2]. SLNs showed spherical shape and mean diameter below 300nm with narrow size dispersion (PdI lower than 0.2) and z-potential around -35 mV; encapsulation percentage was 92% and exhibited in vitro AG controlled and sustained release profile for at least 72h. In vitro transport studies using artificial membranes (Parallel Artificial Membrane Permeability Assay) and hCMEC/D3 cells revealed that SLNs were successful in enhancing the permeation of AG. Fluorescent-SLNs were also developed using fluorescein isothiocyanate for in vivo test in healthy rats. SLNs were administrated by intravenous route and were detected in the brain parenchyma twenty-four and seventy-two hours after administration, by confirming their ability to overcome the BBB.

Financial support was granted by Ente Cassa di Risparmio di Firenze.

[1] Serrano, F. G, Tapia-Rojas, C, Carvajal, F. J, Hancke, J, Cerpa, W, & Inestrosa, N. C. Molecular Neurodegeneration 2014; 9: 61.

[2] De Vringer, T, & De Ronde, H. A. G. Journal of pharmaceutical sciences 1995; 84: 466 – 472.