Efficiency_and_mechanisms_of_sinomenine_HCl_used_as_a_potential_absorption_enhancer.doc

Efficiency and mechanisms of sinomenine HCl used as a potential absorption enhancer Zhilei Lu*, Weiyang Chen, Josias H., Hamman School of Pharmacy, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa *Corresponding author: Zhilei Lu (Dr.) Department of Pharmaceutical Sciences Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa (e-mail: luzj@tut.ac.za) Abstract The objective of the present investigation was to understand efficiency and mechanisms of sinomenine hydrochloride used as absorption enhance agent for difference molecular weight model drugs. The different characteristics model drugs (Cimetidine, Vitamine C, Rutin, Luteolin and Insulin) were used in this study as well as sinomenine hydrochloride was employed as absorption enhance agent. Sinomenine hydrochloride was tested in vitro for their ability to decrease the Trans Epithelial Electrical Resistance (TEER) of Caco-2 cell monolayers compare to N-trimethyl chitosan chloride (TMC) at same concentration. Furthermore, sinomenine hydrochloride was tested as transport enhancer of difference model drugs. In vitro studies showed that sinomenine hydrochloride was able to induce a concentration dependent decrease in the TEER values and a lower cell toxicity of the Caco-2 monolayers. Papp value of all the model drugs show significant increase with sinomenine hydrochloride addition compare to the groups without sinomenine hydrochloride. The mechanisms of sinomenine hydrochloride increase drugs absorption by open the tight junction, inhibition P-gp efflux and anti-degradable, respectively. Introduction Oral drug delivery is considered as the preferred route of administration, but the bioavailability of orally administered macromolecule drugs is usually poor because of the hostile gastric and intestinal environments and also the poor gastrointestinal (GI) mucosal permeability. Co-administer absorption enhancers is one way to improve oral bioavailabilit