In vivo buccal delivery of the peptide drug buserelin with glycodeoxycholate as an absorption enhancer in pigs.

Purpose: To study the potential of buccal delivery of the peptide drug in pigs.

Methods: Intravenous administration and buccal delivery without and with 10 mM sodium glycodeoxycholate (GDC) as absorption enhancer were investigated as a randomised cross-over study in six pigs. The buccal delivery device consisted of an application chamber with a solution of buserelin and was attached to the buccal mucosa for 4 hours using an adhesive patch.

In-vivo buccal delivery of fluorescein isothiocyanate-dextran 4400 with glycodeoxycholate as an absorption enhancer in pigs.

Buccal delivery of fluorescein isothiocyanate labeled dextran 4400 (FD4) was investigated in-vivo in pigs. The delivery device consisted of an application chamber with a solution of FD4 and was adhered to the buccal mucosa for 4 h using an adhesive patch. A randomized crossover study including intravenous administration and buccal delivery without and with 10 mM sodium glycodeoxycholate (GDC) as absorption enhancer was performed in five pigs.

Visualization of diffusion pathways across the stratum corneum of native and in-vitro-reconstructed epidermis by confocal laser scanning microscopy.

Confocal laser scanning microscopy is a technique that permits the direct visualization in unfixed material of diffusion pathways and the cellular distribution of fluorescent markers after topical applications. This approach, in which the tissue specimen is optically sectioned, allows the study of changes in distribution pattern of applied compounds depending on the vehicle, time and depth without the interference of chemical alterations induced by most of the current techniques used for such studies. Using this technique the permeability properties of in-vitro-reconstructed epidermis were compared with those of the native counterpart.

Diffusion rates and transport pathways of fluorescein isothiocyanate (FITC)-labeled model compounds through buccal epithelium.

The aim of this study was to characterize transport of FITC-labeled 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 porcine buccal epithelium by hydrophilic compounds such as the FITC-dextrans is restricted to permeants with a molecular weight lower than 20 kDa.

Visualization of enhancing effects of bile salts on buccal penetration.

The enhancing effects of bile salts on buccal penetration was investigated in vitro using porcine buccal mucosa, correlating permeability changes with histological effects. The permeability of the buccal mucosa to the model compound fluorescein isothiocyanate (FITC) was studied in the presence and absence of bile salts. Light microscopy, freeze-fracture electron microscopy and confocal laser scanning microscopy were used in order to investigate the interaction between the bile salts and the buccal epithelium.