Inducing sustained release and improving oral bioavailability of curcumin via chitosan derivatives-coated liposomes

Liposomes (LPs), a delivery vehicle for stabilizing drugs, the characteristics of being easy to aggregate and fuse limit its application. Polymer coating is a promising way to tackle these issues. In this study, the potential of carboxymethyl chitosan (CMCS) and quaternary ammonium chitosan (TMC)-coated liposomes (CMCS/TMC-LPs) for improving the oral delivery capacity of curcumin (CUR) was explored. CMCS/TMC-LPs were prepared by electrostatic adsorption in a layer-by-layer manner. CMCS/TMC-LPs were spherical and had not obvious change in particle size and morphology after storage at 4 °C for 7 and 14 days. CMCS/TMC-LPs possessed favorable gastric acid tolerance (the cumulative drug release rate <10%) due to stable structure. The hemolysis test and Cell Counting Kit-8 (CCK8) assay appeared satisfactory biocompatibility of CMCS/TMC-LPs. The pharmacokinetics exhibited that oral absolute bioavailability of CUR loaded CMCS/TMC-LPs was about 38%, which was around 6 folds and 3 folds higher than CUR loaded LPs and CUR loaded TMC-LPs, respectively. The in vivo experiments showed that CMCS/TMC-LPs could prolong the retention time of CUR in systemic circulation and generate high level of CUR in liver, spleen and lung. Thus, CMCS/TMC-LPs may be a promising carrier for improving the efficacy and safety of orally administered drugs.