Brain delivery of proteins by the intranasal route of administration: a comparison of cationic liposomes versus aqueous solution formulations.
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.
Department of Pharmaceutical Sciences, Northeastern University, 312 Mugar Building, 360 Huntington Ave., Boston, Massachusetts 02115, USA.
Mattia M
MM
Migliore
Tushar K
TK
Vyas
Robert B
RB
Campbell
Mansoor M
MM
Amiji
Barbara L
BL
Waszczak
D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002412:Cations / Q000737:chemistry; D002463:Cell Membrane Permeability; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D010047:Ovalbumin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002412:Cations; D008081:Liposomes; D010047:Ovalbumin