Andrographolide (AG), the major diterpenoid of Andrographis paniculata (Burm. f.) Wall. ex Nees (Acanthaceae), has received attention due to its pharmacologic activities including protection against damage induced by beta-amyloid , modulation of the formation of amyloid plaques and recovery of spatial memory functions in Alzheimer disease mouse model [1]. The high lipid solubility of AG permits penetration of the blood–brain barrier but it reduces its bioavailability. Continuing our studies on the development of drug delivery systems able to cross the BBB [2], in this work we developed nanosized liposomes to deliver AG and ameliorate its biopharmaceutical properties.
The surface properties of the liposomes were modified by adding Tween 80 (LPs-AG) alone or with didecyldimethylammonium bromide (DDAB) (CLPs-AG) for enhanced penetration into the brain. The mean vesicle size resulted less than 100 nm with low polydispersity index. The entrapment efficiency was about 50%. TEM analyses showed spherical vesicles with smooth bilayer surface. Stability of liposomes was assessed over one-month period as suspension at 4°C and as lyophilized product at 25°C. The release of AG at pH 7.4 was prolonged and sustained and Higuchi model was shown to be the best-fit model to describe the kinetic of release. In vitro permeation studies, both PAMPA and hCMEC/D3 cells, revealed that LPs-AG and CLPs-AG increased the permeability of AG, about an order of magnitude, compared to free AG. Further studies indicated that active processes, in particular caveolae-mediated endocytosis, were involved in the uptake of liposomes.
References:
[1] Serrano FG, et al. Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice. Molecular neurodegeneration 2014; 9 (1): 61.
[2] Graverini G, Piazzini V, et al. Solid lipid nanoparticles for delivery of andrographolide across the blood-brain barrier: in vitro and in vivo evaluation. Colloids and Surfaces B: Biointerfaces 2018; 161: 302-313.