Purpose of the present research was to evaluate in vitro and in vivo potential of gemcitabine (GEM) loaded hyaluronic acid (HA) conjugated PEGylated multi-walled carbon nanotubes (GEM/HA-PEG-MWCNTs) for effective colon cancer targeting. HA was conjugated onto the surface of aminated or PEGylated MWCNTs which were evaluated for size, surface morphology, entrapment efficiency (~90%), in vitro drug release, in vitro cytotoxicity and in vivo performance in Sprague Dawley rats. In vitro release showed that the release rate of GEM in acidic conditions (pH 5.3) was faster than physiological conditions (PBS, pH 7.4) followed by a sustained release pattern. The developed GEM/HA-PEG-MWCNTs indicated significantly less hemolytic toxicity (7.73 ± 0.4%) paralleled to free GEM (18.71 ± 0.44%) and showed higher cytotoxicity against HT-29 colon cancer cell line. The antitumor study assured that GEM/HA-PEG-MWCNTs significantly reduced tumor volume as compared to free GEM and increased survival rate without noticeable loss in body weight. In vivo studies showed an improvement in pharmacokinetics in terms of remarkable escalation in mean residence time, half-life, AUC, AUMC, median survival time in tumor bearing rats treated with GEM/HA-MWCNTs and GEM/HA-PEG-MWCNTs as compared to free GEM (p ˂ 0.001). These outcomes proved engineered MWCNTs as a safe and effective nanomedicine in colon cancer targeting.
Keywords: Gemcitabine; Hyaluronic acid; Multi-walled carbon nanotubes.
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