Brain delivery of proteins by the intranasal route of administration: a comparison of cationic liposomes versus aqueous solution formulations

• Published in: Journal of pharmaceutical sciences Vol. 99; no. 4; p. 1745
• Main Authors: Migliore, Mattia M, Vyas, Tushar K, Campbell, Robert B, Amiji, Mansoor M, Waszczak, Barbara L
• Format: Journal Article
• Language: English
• Published: United States 01-04-2010
• Subjects: Administration, Intranasal; Animals; Brain - metabolism; Cations - chemistry; Cell Membrane Permeability; Liposomes - chemistry; Male; Nanoparticles - chemistry; Ovalbumin - administration & dosage; Ovalbumin - pharmacokinetics; Rats; Rats, Sprague-Dawley
• ISSN: 1520-6017
• DOI: 10.1002/jps.21939

The goal of this research was to evaluate the effectiveness of cationic liposomes for intranasal administration of proteins to the brain. Cationic liposomes were loaded with a model protein, ovalbumin (OVAL), and a 50 microg dose was administered intranasally to rats. In qualitative studies, liposomes were loaded with Alexa 488-OVAL and delivery was assessed by fluorescence microscopy. By 6 and 24 h after administration, Alexa 488-OVAL deposits were widely distributed throughout brain, with apparent cellular uptake in midbrain by 6 h after administration. In quantitative studies, liposomes were loaded with (111)In-OVAL, and distribution to brain and peripheral tissues was monitored by gamma counting at 1, 4, 6, and 24 h after administration. The highest brain concentrations were achieved at the shortest time point, 1 h, for both liposomal and aqueous OVAL. However, the liposomes yielded higher (111)In-OVAL concentrations in brain than (111)In-OVAL in PBS. Moreover, a 2 microg/microL form of liposomal OVAL yielded a higher percentage of dose in brain, and a lower percentage in stomach and intestines, than twice the volume of a 1 microg/microL preparation. Cationic liposomes may provide a novel, noninvasive strategy for delivery of neuroactive proteins to the brain for treatment of central nervous system disorders.