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Polymeric nanoparticles are widely used as targeted carriers for biomacromolecules. In this paper, modified gelatin nanoparticles were prepared and their feasibility as insulin pulmonary administration system was investigated. D: ,L: -glyceraldehyde and poloxamer 188 were used for gelatin nanoparticle preparation. Novel water-in-water emulsion technique was used to prepare insulin-loaded nanoparticles. Morphological examination of insulin-loaded nanoparticles was carried out using scanning electron microscopy (SEM). Intratracheal instillation of insulin-loaded nanoparticles was performed to evaluate animal hypoglycemic effect. With fluorescence labeling of insulin, alveolar deposition and absorption of insulin-loaded nanoparticles were investigated. Histological changes in the lung were also observed to evaluate the safety. From the micromorphology observation, insulin-loaded nanoparticles under gelatin-poloxamer 188 ratio at 1:1 showed smooth and uniform surface, with average particle size 250 nm and Zeta potential -21.1 mV. From animal experiment, insulin-loaded nanoparticles under gelatin-poloxamer 188 ratio at 1:1 promoted insulin pulmonary absorption effectively and showed good relative pharmacological bioavailability. Proved by alveolar deposition result, FITC-insulin-loaded nanoparticle group was characterized by an acute and rapid hypoglycemic effect. In addition, nanoparticles could guarantee the safety of lung by reducing insulin deposition in lung. A transient weak inflammatory response was observed at 1 day after administration. With good physical characterization, high bioavailability, fast and stable hypoglycemic effect, insulin-loaded nanoparticles might be developed as a novel insulin pulmonary system for diabetes therapy.

Background: Gas-filled phospholipid-based ultrasonic microbubbles (PUMs) are widely used in diagnostic imaging. The micro- or nanoparticle size and the physiochemical nature of shell provide the potential for a new way to improve pulmonary absorption for peptides and proteins., Methods: Male Sprague-Dawley rats were fasted for 12 h. Then insulin solution and insulin-PUM mixture solution were administered by intratracheal instillation. The hypoglycemic effect was observed to evaluate insulin absorption after lung administration. Fluorescein isothiocyanate-dextran (molecular mass, 4 kDa) was used as the index of evaluating drug alveolar deposition and absorption by visualization techniques., Results: Administration of insulin solution containing PUMs significantly reduced the blood glucose levels of Sprague-Dawley rats, compared with administration of insulin-only solution. The minimum reductions of the blood glucose concentration produced by insulin solution containing PUMs and by an insulin-only solution reached 60.81% and 34.60% of the initial glucose levels, respectively, and their bioavailabilities relative to subcutaneous injection were 48.58% and 29.09%, respectively. Histopathological study of the lung showed no changes in the morphology of the pulmonary alveoli after administration to these drugs. Only a slight inflammatory cell infiltration in the alveoli could be found in some rats., Conclusion: These results suggested that PUMs might be used as an effective way to improve pulmonary absorption for peptides and proteins.