Amphiphilic α-
tocopherol pullulan polymers (PUTC1, PUTC2, and PUTC3) with different degrees of substitution were synthesized as new carriers for anticancer drugs. The
polymers easily self-assembled into nanomicelles through dialysis method. The critical
micelle concentrations (CMCs) were 38.0, 8.0, and 4.3mg/L for PUTC1, PUTC2, and PUTC3, respectively.
10-Hydroxycamptothecin (
HCPT) used as a model
drug was successfully loaded into the PUTC nanomicelles. Transmission electron microscopy images demonstrated that
HCPT-loaded PUTC nanomicelles were almost spherical and had sizes ranging within 171.5-257.8 nm that increased with increased
HCPT-loading content, as determined by dynamic
laser scattering. The highest encapsulation efficiency of
HCPT in PUTC nanomicelles reached 98.3%. The in vitro release of
HCPT from PUTC
micelles demonstrated sustained release for over 80 h.
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays showed that blank PUTC
micelles were nontoxic to normal cells and that the
HCPT-loaded PUTC2 nanomicelles showed higher cytotoxicity than the free
drug, which was attributed to the enhanced cellular uptake of
drug-loaded nanomicelles. Biodistribution experiments showed that PUTC
micelles provided an excellent approach to rapid
drug transport into cell nuclei. Moreover, the cellular uptake of
micelles was found to be an energy-dependent and actin polymerization-associated endocytic process by endocytosis inhibition experiments. These results suggested that PUTC nanomicelles had considerable potential as a
drug carrier for
drug intracellular delivery in
cancer therapy.