Nanostructured lipid carriers modified with PEGylated carboxymethylcellulose polymers for effective delivery of docetaxel

An amphiphilic carboxymethylcellulose-graft-histidine/methoxypolyethylene glycol (CMP) copolymer was firstly synthesized to modify nanostructured lipid carriers (NLCs), and the impact of this CMP modification on in vitro and in vivo behaviors of NLCs was investigated in detail. An obvious core-shell structure of CMP-coated nanostructured lipid carriers (CNLCs) was observed by a transmission electron microscope (TEM). Docetaxel (DTX) efficiently encapsulated in CNLCs formed 88.7 + 1.11 nm particles with a negative zeta potential of -20.9 +/- 1.11 mV. In vitro release studies indicated that the CMP coating significantly reduced the burst drug release at pH 7.4, whereas DTX-loaded CNLCs (DTX-CNLCs) could release the drug as quickly as DTX-loaded NLCs (DTX-NLCs) at pH 5.0. The pharmacokinetic performances proved that DTX-CNLCs had longer retention times in blood and higher area under the concentration-time curve (AUC) in rats than DTX-NLCs (p < 0.05). Furthermore, cell uptake, cytotoxicity, and cell apoptosis assays in MCF-7 cells consistently demonstrated that no obvious difference was found between DTX-CNLCs and DTX-NLCs (p > 0.05), indicating that this modification did not disturb effective killing of the cancer cells. As expected, DTX-CNLCs exhibited better antitumor effects than DTX-NLCs in the tumor-bearing nude mice (p < 0.05), due to their long circulation effect. Consequently, CNLCs hold great potential for effective delivery of anticancer drugs.