title: Liposomal-benzocaine gel formulation: correlation between in vitro assays and in vivo topical anesthesia in volunteers.
abstract: The aim of the present study was to characterize a liposome-based benzocaine (BZC) formulation designed for topical use on the oral mucosa and to evaluate its in vitro retention and permeation using the Franz-type diffusion cells through pig esophagus mucosa. To predict the effectiveness of new designed formulations during preclinical studies, a correlation between in vitro assays and in vivo efficacy was performed. Liposomal BZC was characterized in terms of membrane/water partition coefficient, encapsulation efficiency, size, polydispersity, zeta potential, and morphology. Liposomal BZC (BL10) was incorporated into gel formulation and its performances were compared to plain BZC gel (B10) and the commercially available BZC gel (B20). BL10 and B10 presented higher flux and retention on pig esophagus mucosa with a shorter lag time, when compared to B20. BZC flux was strongly correlated with in vivo anesthetic efficacy, but not with topical anesthesia duration. The retention studies did not correlate with any of the in vivo efficacy parameters. Thus, in vitro permeation study can be useful to predict anesthetic efficacy during preclinical tests, because a correlation between flux and anesthetic efficacy was observed. Therefore, in vitro assays, followed by in vivo efficacy, are necessary to confirm anesthetic performance.
authors.affiliation: Department of Biochemistry, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil. franzmontan@hotmail.com
authors.forename: Michelle
authors.initials: M
authors.lastname: Franz-Montan
authors.forename: Cintia Maria Saia
authors.initials: CM
authors.lastname: Cereda
authors.forename: Adele
authors.initials: A
authors.lastname: Gaspari
authors.forename: Camila Morais Gonçalves
authors.initials: CM
authors.lastname: da Silva
authors.forename: Daniele Ribeiro
authors.initials: DR
authors.lastname: de Araújo
authors.forename: Cristina
authors.initials: C
authors.lastname: Padula
authors.forename: Patrizia
authors.initials: P
authors.lastname: Santi
authors.forename: Eliene
authors.initials: E
authors.lastname: Narvaes
authors.forename: Pedro Duarte
authors.initials: PD
authors.lastname: Novaes
authors.forename: Francisco Carlos
authors.initials: FC
authors.lastname: Groppo
authors.forename: Eneida
authors.initials: E
authors.lastname: de Paula
mesh_terms: D000287:Administration, Topical; D000772:Anesthesia, Local; D000818:Animals; D001566:Benzocaine / Q000008:administration & dosage* / Q000737:chemistry; D004355:Drug Stability; D004947:Esophagus / Q000166:cytology / Q000187:drug effects; D005782:Gels / Q000008:administration & dosage; D064368:Healthy Volunteers; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D009061:Mouth Mucosa / Q000187:drug effects*; D010316:Particle Size; D013552:Swine
chemical_list: D005782:Gels; D008081:Liposomes; D001566:Benzocaine