betadex and 6-carboxyfluorescein

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.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; beta-Cyclodextrins; Calcitonin; Calcium; Dextrans; Fluorescein-5-isothiocyanate; Fluoresceins; Insulin; Lung; Male; Molecular Weight; Polyethyleneimine; Rats, Sprague-Dawley; Respiratory Tract Absorption

The transdermal transport of cyclodextrins (CD) across porcine epidermis by electroporation was studied. Electroporation increased the permeation of beta-cyclodextrin (BCD) and hydroxy propyl beta-cyclodextrin (HPCD) by several orders of magnitude, relative to passive transport. The presence of BCD and HPCD enhanced the total transport of the test permeants piroxicam and carboxyfluorescein (CF), respectively, from both permeant solutions and suspensions. BCD enhanced the fraction of piroxicam transported across the epidermis into the receiver compartment medium. This was most likely due to the prolonged post-pulse permeability state of the epidermis. The fraction of CF retained in the epidermis was increased by HPCD. The rate of diffusion of CF from epidermis into the receiver compartment was decreased by the presence of HPCD, apparently due to the aggregate forming tendency of HPCD. The in vivo delivery of CF by electroporation in mice demonstrated the potential of HPCD for sustaining the transdermal absorption rate of hydrophilic molecules.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Cutaneous; Animals; beta-Cyclodextrins; Biological Transport; Diffusion; Drug Carriers; Electroporation; Fluoresceins; Piroxicam; Skin; Skin Absorption; Surface-Active Agents; Swine