Journal
CARBOHYDRATE POLYMERS
Volume 111, Issue -, Pages 753-761Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2014.04.095
Keywords
O-carboxymethylated chitosan; Cholic acid; Glycyrrhetinic acid; Self-aggregates
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Funding
- Natural Science Foundation of Shandong Province, China [ZR2011HM026]
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O-carboxymethyl chitosan (OCMC) was firstly decorated with cholic acid (CA) to acquire an amphiphilic polymer under alkaline condition. Then glycyrrhetinic acid (GA) was conjugated to the polymer via a succinate linker and finally treated with NaCO3 solution to obtain new conjugates for potential liver targeted delivery. These conjugates formed uniform aggregates with low critical aggregation concentrations (0.028-0.079 mg/mL) in PBS. The average diameter of cholic acid modified carboxymethyl chitosan (CMCA) aggregates (110-257 nm) decreased with the increase of CA substitution degree and became slightly larger after GA modification. Negative zeta potential (-15 mV) of GA decorated CMCA (GA-CMCA) revealed that the formation of negatively charged shells and spherical morphology was observed under transmission electron microscopy. Furthermore, hemolysis test, in vitro cytotoxicity assay and cellular uptake study all demonstrated the safety and feasibility of these conjugates as a promising carrier for liver targeted drug delivery. (C) 2014 Elsevier Ltd. All rights reserved.
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