  New mixed cationic liposomes based on L-{\alpha}-phosphatidylcholine and
dihexadecylmethylhydroxyethylammonium bromide (DHDHAB) were designed to
overcome the BBB crossing by using the intranasal route. Synthesis and
self-assembly of DHDHAB were performed. A low critical association
concentration (0.01 mM), good solubilization properties toward hydrophobic dye
Orange OT and antimicrobial activity against gram-positive bacteria
Staphylococcus aureus (MIC=7.8 {\mu}g.mL-1) and Bacillus cereus (MIC=7.8
{\mu}g.mL-1), low hemolytic activities against human red blood cells (less than
10%) were achieved. Conditions for preparation of cationic vesicle and mixed
liposomes with excellent colloidal stability at room temperature were
determined. The intranasal administration of rhodamine B-loaded cationic
liposomes was shown to increase bioavailability into the brain in comparison to
the intravenous injection. The cholinesterase reactivator, 2-PAM, was used as
model drug for the loading in cationic liposomes. 2-PAM-loaded cationic
liposomes displayed high encapsulation efficiency (~ 90 %) and hydrodynamic
diameter close to 100 nm. Intranasally administered 2-PAM-loaded cationic
liposomes were effective against paraoxon-induced acetylcholinesterase
inhibition in the brain. 2-PAM-loaded liposomes reactivated 12 +/- 1% of brain
acetylcholinesterase. This promising result opens the possibility to use
marketed positively charged oximes in medical countermeasures against
organophosphorus poisoning for reactivation of central acetylcholinesterase by
implementing a non-invasive approach, via the "nose-brain" pathway.

Medical Physics;Soft Condensed Matter;Biological Physics