title: Mathematical modelling of the transport of hydroxypropyl-β-cyclodextrin inclusion complexes of ranitidine hydrochloride and furosemide loaded chitosan nanoparticles across a Caco-2 cell monolayer.
abstract: Chitosan nanoparticles (CS-NPs) have been used to enhance the permeability of furosemide and ranitidine hydrochloride (ranitidine HCl) which were selected as candidates for two different biopharmaceutical drug classes having low permeability across Caco-2 cell monolayers. Drugs loaded CS-NPs were prepared by ionic gelation of CS and pentasodium tripolyphosphate (TPP) which added to the drugs inclusion complexes with hydroxypropyl-β-cyclodextrin (HP-βCD). The stability constants for furosemide/HP-βCD and ranitidine HCl/HP-βCD were calculated as 335 M(-1) and 410 M(-1), whereas the association efficiencies (AE%) of the drugs/HP-βCD inclusion complexes with CS-NPs were determined to be 23.0 and 19.5%, respectively. Zetasizer and scanning electron microscopy (SEM) were used to characterise drugs/HP-βCD-NPs size and morphology. Transport of both nano and non-nano formulations of drugs/HP-βCD complexes across a Caco-2 cell monolayer was assessed and fitted to mathematical models. Furosemide/HP-βCD-NPs demonstrated transport kinetics best suited for the Higuchi model, whereas other drug formulations demonstrated power law transportation behaviour. Permeability experiments revealed that furosemide/HP-βCD and ranitidine HCl/HP-βCD nano formulations greatly induce the opening of tight junctions and enhance drug transition through Caco-2 monolayers.
authors.affiliation: Department of Medical Nanotechnology, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Armin
authors.initials: A
authors.lastname: Sadighi
authors.forename: S N
authors.initials: SN
authors.lastname: Ostad
authors.forename: S M
authors.initials: SM
authors.lastname: Rezayat
authors.forename: M
authors.initials: M
authors.lastname: Foroutan
authors.forename: M A
authors.initials: MA
authors.lastname: Faramarzi
authors.forename: F A
authors.initials: FA
authors.lastname: Dorkoosh
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D001692:Biological Transport; D018938:Caco-2 Cells; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D005665:Furosemide / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D010539:Permeability; D011122:Polyphosphates / Q000737:chemistry; D011899:Ranitidine / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D019108:Tight Junctions / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D011122:Polyphosphates; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D005665:Furosemide; D011899:Ranitidine; D048271:Chitosan; C005692:triphosphoric acid