effect of sodium glycodeoxycholate topical application at different concentrations as a drug absorptive enhancer on rabbit buccal mucosa [transmission electron microscopic study]

ABSTRACT

To avoid the hepatic first pass drugs effects, different absorption enhancers were used to achieve the optimal drug delivery via the buccal mucosa. Twenty male rabbits were used in this study weighing from 400-500 gm. These animals were divided into four groups; the 1[st] one [comprised 2 animals] was considered as a control group, while the 2[nd], 3[rd] and the 4[th] [6 animals each] were considered as experimental groups. A patch material was adhered to the buccal mucosa opposite to the upper first molar of the control group. Also the patch materials soaked with sodium glycodeoxycholate [GDC] solution 1%, 2% and 3% were adhered to the buccal mucosa in the same site of the 2[nd] 3[rd] and 4[th] experimental groups respectively, one hour daily for three weeks. The specimens were taken from the buccal mucosa after sacrification of the animals to be prepared for ultra- structural examination by transmission electron microscope. The results had revealed that the application of 1% of GDC was the safest concentration than 2% and 3% which was the most toxic one as revealed by the presence of deleterious and dramatic harmful ultrastructural changes in desmosmal, hemidesmosomal attachments and in the mitochondriae. These harmful changes had comprised the loss of desmosmal, hemidesmosomal attachments and lysis of mitochondrial matrix and its cristae with the presence of electron dense drug material inside the mitochondriae and in the connective tissue around blood capillaries associated with collagen fibers degeneration. In contradictory, the 1% GDC concentration had passed intercellulary without these pervious harmful intracellular changes indicating that the pathway of GDC 1% concentration is passing through the buccal mucosa intercellulary without intracellular leakage of its drug material. Thus we can concluded that the absorption enhancement is no longer the main problem but instead of that; the safety of the enhancers, the route of administration and the concentration effect relationship of the enhancer are important issues to achieve optimal drug absorption enhancement. So GDC at 1% concentration may improve delivery of various chronic administration of drugs into systemic circulation through buccal mucosa