Category: Formulation and Quality
Purpose: The modification of tight junction between epithelial cells make it possible to investigate a permeation enhancer of therapeutic agents. The purpose of this study was to evaluate the biological activity of tight junction modulator co-administered with a fructose polymer on enhancing the nasal and duodenal administration of atenolol.
Methods: The permeability enhancing effect of the C-terminal modified fragment of Zonula occludens toxin (Phe-Cys-Ile-Gly-Arg-Leu-NH2) with/without levan of the fructose polymer on the transport of atenolol (2 mg/kg) in each intranasal and intra-duodenal administration examined after the following groups. i.e., atenolol alone, atenolol/levan (0.5%), atenolol/peptide (2.5mg/kg), atenolol/levan/peptide for the intranasal study and atenolol alone, atenolol/levan (0.5%), atenolol/levan/peptide (5mg/kg), atenolol/levan/peptide (10mg/kg) for the intra-duodenal study. In addition, atenolol alone, atenolol/peptide (10mg/kg), atenolol/peptide/levan (0.1%), atenolol/peptide/levan (0.5%) for the fructose polymer study were prepared and administered intra-duodenally to male SD rats (280-300g, n=3-5), respectively.
Results: The C-terminal modified peptide resulted in statistically significant improvement in permeation of atenolol compared to the control in both nasal and duodenal administration. Also, the permeability enhancing effect of the C-terminal modified peptide was significantly promoted by the fructose polymer, levan. The nasal administration of C-terminal modified peptide (2.5mg/kg) with levan led to 2.02-fold increase of AUC0–240min and 2.33-fold increase of Cmax of atenolol. There was a 2.19-fold (p< 0.01) increase in AUC0-240min and the Cmax was statistically increased by 2.49-fold (p< 0.05) after intra-duodenal administration of atenolol with C-terminal modified peptide (10mg/kg) and levan (0.5%). On the contrary, levan alone did not produce an improvement of atenolol permeation in both administrations.
Conclusion: The results showed the intensive effectiveness of C-terminal modified peptide as a permeation enhancer in the support of levan in enhancing intranasal and intra-duodenal permeation of atenolol. Thus, this tight junction modulated permeation enhancer with levan may allow the development of the mucosal drug delivery of low-bioavailability therapeutic agents when administered concurrently.