Preparation and characterization of starch/cyclodextrin bioadhesive microspheres as platform for nasal administration of Gabexate Mesylate (Foy) in allergic rhinitis treatment.
Bioadhesive and biodegradable microspheres were obtained by chemical cross-linking with epichlorohydrin of an alkaline solution of a mixture of starch and alpha-, beta-, or gamma-cyclodextrin (CyD). Microspheres were characterized by scanning electron microscopy, swelling degree, and water retention. The percentage of the effective CyD in microspheres was estimated by measuring the amount of iodine and typical organic compounds (TOCs) retained in the hydrophobic cavity of CyD. Gabexate Mesylate (trade name Foy); GM), an antiallergic drug, was included in microspheres by soaking in an aqueous solution containing the drug, followed by solvent evaporation or lyophilization. UV, IR, and DSC data indicated that despite the fact that GM is a hydrophilic drug, its hydrophobic moiety close to the benzene ring is able to penetrate the CyD cavity and to form stable inclusion complexes. Values of the association equilibrium constant for GM binding to CyD, obtained by UV differential spectroscopy, indicated that the affinity of the drug for alpha- and gamma-CyD is higher than that for beta-CyD. In vitro, GM was gradually released during 1h. Even if the release rate of the drug is relatively fast, the microspheres might actually provide the best platform since the material adheres to the nasal mucosa which was proved by adhesion tests. The GM integrity was checked by comparing its anti-trypsin activity before and after release.
Department of Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara, 17-19, I-44100, Ferrara, Italy.
Gheorghe
G
Fundueanu
Marieta
M
Constantin
Alessandro
A
Dalpiaz
Fabrizio
F
Bortolotti
Rita
R
Cortesi
Paolo
P
Ascenzi
Enea
E
Menegatti
D000269:Adhesives / Q000138:chemical synthesis / Q000737:chemistry; D000281:Administration, Intranasal; D000818:Animals; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000737:chemistry*; D003270:Contraceptive Agents / Q000138:chemical synthesis / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D016670:Gabexate / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D007700:Kinetics; D008297:Male; D008422:Materials Testing; D008657:Metabolic Clearance Rate; D008863:Microspheres; D051381:Rats; D012220:Rhinitis / Q000188:drug therapy; D013213:Starch / Q000737:chemistry*; D013499:Surface Properties; D014018:Tissue Distribution
D000269:Adhesives; D020099:Coated Materials, Biocompatible; D003270:Contraceptive Agents; D003505:Cyclodextrins; D016670:Gabexate; D013213:Starch