title: Evaluation of different pig oral mucosa sites as permeability barrier models for drug permeation studies.
abstract: The objective of the present study was to investigate the influence of preparation and storage conditions on the histology and permeability of different parts of porcine oral mucosa used for in vitro studies of transbuccal formulations. Fresh and frozen (-20°C and -80°C, with or without cryoprotectant) epithelia of porcine palatal, gingival, dorsum of the tongue, and buccal mucosa were submitted for histological analyses to determine the effects of storage conditions on barrier integrity. Permeation of lidocaine hydrochloride (used as a hydrophilic model drug) across fresh and previously frozen oral epithelium was measured in order to evaluate the barrier function. Histological evaluation demonstrated that the oral epithelium was successfully separated from the connective tissue, except for gingival mucosa. After storage under different conditions, all tissues presented desquamation of superficial layers and spherical spaces induced by the freezing process. The permeability of lidocaine hydrochloride varied among the fresh oral mucosa and generally increased after freezing. In conclusion, fresh epithelium from the buccal and dorsum of the tongue mucosa should be used for in vitro studies investigating hydrophilic drug transport when these are the desired clinical application sites. However, when the palate is the target site, both fresh and frozen (for up to 4weeks, without addition of cryoprotectant) samples could be used. The addition of glycerol as a cryoprotectant should be avoided due to increased lidocaine hydrochloride permeability.
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil. Electronic address: michelle@fop.unicamp.br.
authors.forename: Michelle
authors.initials: M
authors.lastname: Franz-Montan
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.
authors.forename: Luciano
authors.initials: L
authors.lastname: Serpe
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.
authors.forename: Claudia Cristina Maia
authors.initials: CC
authors.lastname: Martinelli
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.
authors.forename: Camila Batista
authors.initials: CB
authors.lastname: da Silva
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.
authors.forename: Cleiton Pita Dos
authors.initials: CP
authors.lastname: Santos
authors.affiliation: Department of Morphology, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.
authors.forename: Pedro Duarte
authors.initials: PD
authors.lastname: Novaes
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Volpato
authors.affiliation: Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Eneida
authors.initials: E
authors.lastname: de Paula
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo - USP, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Renata Fonseca Vianna
authors.initials: RF
authors.lastname: Lopez
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.
authors.forename: Francisco Carlos
authors.initials: FC
authors.lastname: Groppo
mesh_terms: D000779:Anesthetics, Local / Q000378:metabolism*; D000818:Animals; D003451:Cryoprotective Agents / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005615:Freezing; D005990:Glycerol / Q000494:pharmacology; D008012:Lidocaine / Q000378:metabolism*; D009061:Mouth Mucosa / Q000033:anatomy & histology / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D013048:Specimen Handling / Q000379:methods; D013552:Swine
chemical_list: D000779:Anesthetics, Local; D003451:Cryoprotective Agents; D008012:Lidocaine; D005990:Glycerol
keywords: Diffusion; In vitro model; Oral mucosa drug delivery; Permeability