Transbuccal delivery of 2′,3′-dideoxycytidine: in vitro permeation study and histological investigation

Abstract

Permeation of 2′,3′-dideoxycytidine (ddC), an ionic compound, through buccal mucosa was investigated in this in vitro study to identify the major permeation barrier within the epithelium of buccal mucosa and explore the feasibility of transbuccal delivery of ddC. In vitro permeation of ddC across porcine buccal mucosa was conducted in isotonic McIlvaine buffer solution (IMB) using in-line flow through diffusion cells at 37 °C. Sodium glycodeoxycholate (GDC) was used as the permeation enhancer in the permeation enhancement studies. Light microscopy was used in the histological studies of buccal tissue. The steady-state flux of ddC permeating through buccal mucosa increased linearly ( R 2=0.96, P<0.05) as the donor concentration of ddC was increased from 1 to 20 mg/ml. The permeabilities for the full thickness buccal mucosa, the epithelium, and the connective tissue were determined to be 1.75±0.74×10 −7, 2.90±1.86×10 −7, and 3.49±1.19×10 −6 cm/s, respectively. The permeability of ddC was significantly ( P<0.05) enhanced by GDC at a concentration of 4 mM. The histological study revealed that the thickness of epithelium was greatly reduced after buccal tissues were immersed in IMB for 12 and 24 h but the basal lamina remained intact even after 24 h. A bilayer diffusion model was established to quantitatively describe the contributions of the epithelium and the connective tissue to the permeation barrier. In conclusion, ddC permeated through buccal mucosa by passive diffusion over the range of concentrations examined. The basal lamina layer within the epithelium of buccal mucosa acted as an important barrier to the permeation of ddC. GDC effectively enhanced the buccal permeability of ddC. The transbuccal delivery is a potential route for the administration of ddC.