Solid lipid nanoparticles modified with chitosan oligosaccharides for the controlled release of doxorubicin

Solid lipid nanoparticles (SLN) modified with chitosan oligosaccharide was prepared by solvent diffusion method and subsequent ionic interaction. Using doxorubicin as a model drug, the effects of amount and molecular weight of chitosan oligosaccharide, and its crosslink degree by glutaraldehyde on the physicochemical properties of nanoparticles were investigated. After modification with chitosan oligosaccharide, the zeta potential of nanoparticles changed from about −20 mV to above 30 mV, and the drug loading could be improved from 6.76% to 22.3%. In vitro drug release tests showed the burst release of SLN could be significantly reduced by the chitosan oligosaccharide modification, and the release rate could be controlled by changing the molecular weight of chitosan oligosaccharide and the crosslink degree. In vitro antitumor activity tests indicated the SLN could mediate the cellular internalization of doxorubicin, and the chitosan oligosaccharide modification and crosslink could further improve the cellular uptake and cytotoxicity of doxorubicin.