Herein, we developed a magnetic drug delivery system based on magnetic Fe 3 O 4 nanoparticles with double shells of modified salep polysaccharide for the delivery of doxorubicin (Dox). The drug-loaded nanocarrier was synthesized in an easy way, and large amounts of drug molecules were loaded into the nanocarrier. The drug-loaded nanocarrier showed excellent pH responsibility in vitro, and large amounts of Dox were released at lower pH (60% release), whereas the nanocarrier was stable at neutral pH. The hemolysis assay results showed that the nanocarrier has negligible hemolytic effects on human red blood cells and showed good biocompatibility. Moreover, the result of coagulation assays showed that the nanocarrier was not active in any coagulation pathways. Cytotoxicity assays of nanocarrier and drug-loaded nanocarrier toward HeLa cells demonstrated that the nanocarrier has negligible toxicity, whereas the drug-loaded nanocarrier kills more than 90% of cells during 48 h. The flow cytometry analysis also showed that the uptake of drug-loaded nanocarrier into the cancerous cells is time-dependent and higher concentrations of drug internalized into the cells at longer incubation time. On the basis of the results, we suggest that the present nanocarrier can be applicable for in vivo drug delivery as an easy-made and cheap nanocarrier.
Two pH-responsive
polysaccharide-based magnetite nanocarriers have
been developed from modified salep and PEGylated chitosan decorated
onto the surface of magnetite nanoparticles for active loading and
targeted delivery of doxorubicin. The first nanocarrier was formed
via imine bond formation and electrostatic hydrogen bonding interactions
between dialdehyde salep-modified magnetite nanoparticles and DOX
in a one-layered nanocarrier fashion. Subsequently, PEGylated chitosan
was used as a second layer on the surface of the first nanocarrier,
mainly by the same interactions, producing a double-layered polysaccharide-based
nanocarrier. In vitro release studies indicated that
the use of PEGylated chitosan as the second shell provides more control
on the rate and amount of DOX release and makes double-layered nanocarrier
more pH-sensitive. Magnetic heating capacity of double-layered nanocarrier
was investigated and release profile under AMF (42 °C, magnetically
induced) showed a good improvement in the time and amount of DOX release. In vitro MTT assays depicted that the DOX-loaded double-layered
nanocarrier produces a large cytotoxic response to HeLa cells, which
is comparable with free DOX in higher concentration. DOX-free double-layered
nanocarrier also exhibited low cytotoxicity against normal cells,
an indication of their excellent biocompatibility. Application of
AMF also showed a large effect on the cytotoxicity of the nanocarrier
rather than without AMF condition. Investigation on cellular uptake
of nanocarrier revealed the high targeting ability of nanocarrier
toward HeLa cells, especially in the presence of AMF. Blood compatibility
investigations indicated that hemolysis of RBCs and coagulation times
fall into the normal range for blood in the presence of DOX-free and
DOX-loaded double-layered nanocarrier.
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