Microspheres containing lipid/chitosan nanoparticles complexes for pulmonary delivery of therapeutic proteins

Chitosan/tripolyphosphate nanoparticles have already been demonstrated to promote peptide absorption through several mucosal surfaces. We have recently developed a new drug delivery system consisting of complexes formed between preformed chitosan/tripolyphosphate nanoparticles and phospholipids, nam...

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Bibliographic Details
Published in:European journal of pharmaceutics and biopharmaceutics 2008-05, Vol.69 (1), p.83-93
Main Authors: Grenha, Ana, Remuñán-López, Carmen, Carvalho, Edison L.S., Seijo, Begoña
Format: Article
Language:English
Subjects:
Biological and medical sciences
Chemistry, Pharmaceutical - methods
Chitosan - chemistry
Chitosan nanoparticles
Drug Carriers
Drug Compounding - methods
Drug Delivery Systems
Dry powders
General pharmacology
Insulin - chemistry
Lipids - chemistry
Lung - drug effects
Medical sciences
Microscopy, Electron, Scanning
Microspheres
Nanoparticles - chemistry
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Phospholipids
Polyphosphates - chemistry
Powders
Pulmonary delivery
Spray-drying
Technology, Pharmaceutical - methods
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Summary:Chitosan/tripolyphosphate nanoparticles have already been demonstrated to promote peptide absorption through several mucosal surfaces. We have recently developed a new drug delivery system consisting of complexes formed between preformed chitosan/tripolyphosphate nanoparticles and phospholipids, named as lipid/chitosan nanoparticles (L/CS-NP) complexes. The aim of this work was to microencapsulate these protein-loaded L/CS-NP complexes by spray-drying, using mannitol as excipient to produce microspheres with adequate properties for pulmonary delivery. Results show that the obtained microspheres are spherical and present appropriate aerodynamic characteristics for lung delivery (aerodynamic diameters around 2–3 μm and low apparent tap density of 0.4–0.5 g/cm 3). The physicochemical properties of the L/CS-NP complexes are affected by the phospholipids composition. Phospholipids provide a controlled release of the encapsulated protein (insulin), which was successfully associated to the system (68%). The complexes can be easily recovered from the mannitol microspheres upon incubation in aqueous medium, maintaining their morphology and physicochemical characteristics. Therefore, this work demonstrates that protein-loaded L/CS-NP complexes can be efficiently microencapsulated, resulting in microspheres with adequate properties to provide a deep inhalation pattern. Furthermore, they are expected to release their payload (the complexes and, consequently, the encapsulated macromolecule) after contacting with the lung aqueous environment.
ISSN:0939-6411
1873-3441
DOI:10.1016/j.ejpb.2007.10.017