Microencapsulated chitosan nanoparticles for pulmonary protein delivery: In vivo evaluation of insulin-loaded formulations

• Published in: Journal of controlled release Vol. 157; no. 3; pp. 383 - 390
• Main Authors: Al-Qadi, S., Grenha, A., Carrión-Recio, D., Seijo, B., Remuñán-López, C.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 10-02-2012; Elsevier
• Subjects: Animals; Biological and medical sciences; Blood Glucose - analysis; chitosan; Chitosan - administration & dosage; Chitosan - chemistry; Chitosan nanoparticles; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Compounding; Dry powders; gelation; General pharmacology; glucose; glycemic effect; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - chemistry; In vivo administration; in vivo studies; insulin; Insulin - administration & dosage; Insulin - chemistry; Lung - metabolism; Lung distribution; lungs; Male; mannitol; Mannitol - administration & dosage; Mannitol - chemistry; Medical sciences; microencapsulation; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Powders; Pulmonary protein delivery; Rats; Rats, Sprague-Dawley; zeta potential; In vivo administration; Pulmonary protein delivery; Chitosan nanoparticles; Dry powders; Lung distribution; Evaluation; Pharmaceutical technology; Nanoparticle; Lung; Polymer; Intrapulmonary administration; Insulin; Powder; Protein; In vivo; Formulation; Distribution; Microparticle; Oside polymer; Chitosan; Pharmacokinetics
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2011.08.008

This work presents a new dry powder system consisting of microencapsulated protein-loaded chitosan nanoparticles (CS NPs). The developed system was evaluated in vivo in rats in order to investigate its potential to transport insulin (INS), a model protein, to the deep lung, where it is absorbed into systemic circulation. The INS-loaded CS NPs were prepared by ionotropic gelation and characterized for morphology, size, zeta potential, association efficiency and loading capacity. Afterwards, the NPs were co-spray dried with mannitol resulting in a dry powder with adequate aerodynamic properties for deposition in deep lungs. The assessment of the plasmatic glucose levels following intratracheal administration to rats revealed that the microencapsulated INS-loaded CS NPs induced a more pronounced and prolonged hypoglycemic effect compared to the controls. Accordingly, the developed system constitutes a promising alternative to systemically deliver therapeutic macromolecules to the lungs, but it can also be used to provide a local effect.
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