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The purpose of the present study was to develop a novel oral absorption enhancer and nanocarrier for oral drug delivery.Curcumin(Cur), the principal bioactive component in turmeric, is speculated to potentially increase drug absorption by inhibition of intestinal P-glycoprotein-mediated secretion.However, the oral bioavailability of curcumin is generally poor due to its instability and insolubility, which may limit its clinical application.Carboxymethyl chitosan(CMCS) is a safe chitosan derivative with improving effect in oral drug absorption.In addition, it contains a large number of active groups, which can be easily modified by chemical reactions.Therefore, we hypothesize that the combination of Cur and CMCS by chemical bonding might be more efficient in promoting oral absorption, while increasing the solubility and stability of Cur.Firstly, a novel nanomaterial: curcumin-carboxymethyl chitosan(CNC) conjugate was synthesized via amid condensation reaction and Schiff base reaction.The chemical structure of CNC conjugate was characterized by UV and 1H NMR and the degree of substitution of Cur was in the range of 1.23 ~10.20 %.More importantly, amphiphilic CNC conjugates, which were found to be spherical in shape with particle sizes in the range of 240.0 ~ 279.9 nm and a narrow size distribution, have markedly increased the stability and water solubility of Cur.Furthermore, mixed polymeric micelles (MPMs) that comprised of CNC conjugate and LHR conjugate (low molecular weight heparin-all-trans-retinoid acid conjugate, a novel amphiphilic nanocarrier which was developed in our previous study) were prepared.CsA (Cyclosporin A)-loaded mixed polymeric micelles (CsA-CNC/LHR MPMs) were prepared by the dialysis method, with high drug loading 25.45 % and particle sizes around 201.2 nm.In situ single pass perfusion studies in rats and pharmacokinetic study were performed to investigate the enhancing ability of CNC conjugates and CsA-CNC/LHR MPMs in comparison with verapamil (a typical P-gp inhibitor).The results indicated that both CsA plus CNC conjugate and CsA-loaded CNC/LHR MPMs achieved significantly higher Ka and Peff than CsA suspensions in ratsduodenum and jejunum.Various concentrations of CNC conjugates were shown to increase the intestinal absorption of CsA, but the enhancing effects of CNC conjugates was weaker than that of CsA-CNC/LHR MPMs.Moreover, pharmacokinetic studies yielded similar results.The pharmacokinetic profiles indicated that CNC conjugate and CNC/LHR MPMs contributed to an extended circulation of CsA, where AUC and MRT of CsA plus CNC conjugate and CsA-CNC/LHR MPMs were significantly increased compared with CsA suspensions.This remarkable enhancement of the oral absorption of CsA by CNC conjugate might be due to a combination of multiple factors such as increased mucosal adhesion and inhibition of P-gp efflux system.On the other hand, the effect of CNC/LHR MPMs on enhancing the absorption of CsA might have resulted from the great capability in solubilization of CsA by LHR micelles, the combined effects which contributed by CNC conjugate mentioned above, and the transport of CsA-CNC/LHR MPMs via a P-gp-independent way.These results suggest that CNC conjugates can be considered as a promising gastrointestinal absorption enhancer as well as an excellent component of mixed nanocarriers for oral drug delivery systems.Based on the obtained results, it is also suggested that CsA-CNC/LHR MPMs might be a potentially applicable tool for enhancing the oral absorption of insoluble drugs and P-gp substrates.