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Brain delivery of proteins by the intranasal route of administration: A comparison of cationic liposomes versus aqueous solution formulations
- Source :
- Journal of Pharmaceutical Sciences. 99:1745-1761
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- 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.
- Subjects :
- Male
Cell Membrane Permeability
Ovalbumin
Stereochemistry
Pharmaceutical Science
Pharmacology
Blood–brain barrier
Rats, Sprague-Dawley
Route of administration
Pharmacokinetics
Cations
medicine
Animals
Distribution (pharmacology)
Cationic liposome
Administration, Intranasal
Liposome
biology
business.industry
digestive, oral, and skin physiology
Brain
Rats
medicine.anatomical_structure
Liposomes
biology.protein
Nanoparticles
Nasal administration
business
Subjects
Details
- ISSN :
- 00223549
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- Journal of Pharmaceutical Sciences
- Accession number :
- edsair.doi.dedup.....3f8768f3e54de15b260fb8ea61ef2511