title: Recent advances in buccal drug delivery and absorption--in vitro and in vivo studies.
abstract: In the first part of this study, the aim was to characterize transport of fluorescein isothiocyanate (FITC)-labelled dextrans of different molecular weights as model compounds for peptides and proteins through buccal mucosa. The penetration of these dextrans through porcine buccal mucosa (a nonkeratinized epithelium, comparable to human buccal mucosa) was investigated by measuring transbuccal fluxes and by analyzing the distribution of the fluorescent probe in the epithelium, using confocal laser scanning microscopy for visualizing permeation pathways. The results revealed that passage of hydrophilic compounds such as the FITC-dextrans through porcine buccal epithelium is restricted to permeants with a molecular weight lower than 20 kDa. The permeabilities of buccal mucosa for the 4 and 10 kDa FITC-dextran (of the order of 10(-8) cm/s) were not significantly different from each other or from the much smaller compound FITC. The confocal images of the distribution pattern of FITC-dextrans showed that the paracellular route is the major pathway through buccal epithelium. In the in vivo part of this study, buccal delivery of FITC-labelled dextran 4400 (FD4) and the peptide drug buserelin was investigated in vivo, in pigs. The delivery device consisted of an application chamber with a solution of FD4 or buserelin, and was attached to the buccal mucosa for 4 h using an adhesive patch. A randomized cross-over study including intravenous administration and buccal delivery without and with 10 mM sodium glycodeoxycholate (GDC) as an absorption enhancer was performed in pigs. After buccal administration, steady-state plasma levels were rapidly achieved. Co-administration of 10 mM GDC increased the absolute bioavailability from 1.8+/-0.5 to 12.7+/-2.0% for FD4. From the present studies, it is concluded that buccal administration is a suitable route for the delivery for macromolecules and hydrophilic compounds such as peptide drugs.
authors.affiliation: Leiden/Amsterdam Center for Drug Research, Division of Pharmaceutical Technology, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands. junginge@chem.leidenuniv.nl
authors.forename: H E
authors.initials: HE
authors.lastname: Junginger
authors.forename: J A
authors.initials: JA
authors.lastname: Hoogstraate
authors.forename: J C
authors.initials: JC
authors.lastname: Verhoef
mesh_terms: D000818:Animals; D002610:Cheek; D003911:Dextrans / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004357:Drug Synergism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D009061:Mouth Mucosa; D010539:Permeability; D012869:Skin Absorption; D012995:Solubility; D013552:Swine; D014867:Water / Q000737:chemistry
chemical_list: D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D014867:Water; D016650:Fluorescein-5-isothiocyanate