Trimethylated chitosan derivatives are effective and safe penetration enhancers for oral peptide drug delivery and absorption

Peptide analogues are poorly absorbed across the intestinal epithelia becau se of the barrier function of tight junctions, which seal the paracellular routes and only allow the passage of small hydrophilic compounds. This resu lts in very low levels of bioavailability when these hydrophilic peptide dr ugs are administered per os. The present study investigated the effect of N -trimethyl chitosan chloride, used as a novel polymeric absorption enhancer , on the intestinal absorption of two peptide drugs, buserelin and octreoti de. N-trimethyl chitosan chloride is the quaternised derivative of chitosan , which is endowed with superior aqueous solubility in a broader pH range a nd with permeation enhancing properties, when compared with chitosan itself . This polymer does not exert any cytotoxic effects on the intestinal epith elia. For experiments using buserelin, the duodenum of rats was chosen as t he site of delivery, either in a solution or as a gel concomitantly adminis tered with N-trimethyl chitosan chloride, when compared to the administrati on of solutions containing the peptide drugs only (controls). The co-admini stration of both peptide drugs with 1.0% (w/v) chitosan hydrochloride at a neutral pH value did not result into elevated peptide absorption when compa red to controls, as chitosan hydrochloride flocculates at this pH value.