Abstract
Effects of hydroxypropyl-β-cyclodextrin grafted polyethylenimine (HP-β-CD-PEI) including HP-β-CD-PEI600, HP-β-CD-PEI1800, HP-β-CD-PEI10000 on the pulmonary absorption of insulin, calcitonin, 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate dextrans (FDs) with various molecular weights (FD4, FD10 and FD70) were examined by an pulmonary absorption study in rats. Pulmonary absorptions of these poorly absorbable drugs were significantly enhanced by HP-β-CD-PEI1800 and HP-β-CD-PEI10000, and HP-β-CD-PEI1800 with the concentration of 5% (w/v) provided maximal absorption enhancing effect on pulmonary absorption of these model drugs. The toxicity study demonstrated that HP-β-CD-PEI did not induce any toxic action to rat pulmonary membranes. In addition, zeta potential of insulin solution changed to positive by addition of various HP-β-CD-PEI, meanwhile, the degree of positive charge was linearly correlated with absorption enhancing effect of HP-β-CD-PEI, suggesting that positive charge of HP-β-CD-PEI might be related to their absorption enhancing mechanisms for enhancing pulmonary absorption of insulin in rats. In conclusion, HP-β-CD-PEI is a potential and safe absorption enhancer for improving absorption of hydrophilic macromolecules especially peptide and protein drugs by pulmonary delivery.
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