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ZOU Ai-feng, HUO Mei-rong, ZHOU Jian-ping, YIN Xiao-qiang, YAO Cheng-li, ZHU Qin-nü, ZHANG Min, REN Jin-shan. Octreotide-mediatedN-octyl-O,N-carboxymethyl chitosan micelles:preparation,characterization and research as doxorubicin delivery vectors[J]. Journal of China Pharmaceutical University, 2011, 42(2): 124-130.
Citation: ZOU Ai-feng, HUO Mei-rong, ZHOU Jian-ping, YIN Xiao-qiang, YAO Cheng-li, ZHU Qin-nü, ZHANG Min, REN Jin-shan. Octreotide-mediatedN-octyl-O,N-carboxymethyl chitosan micelles:preparation,characterization and research as doxorubicin delivery vectors[J]. Journal of China Pharmaceutical University, 2011, 42(2): 124-130.

Octreotide-mediatedN-octyl-O,N-carboxymethyl chitosan micelles:preparation,characterization and research as doxorubicin delivery vectors

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  • The aims of this study were to prepare doxorubicin-loaded N-octyl-O,N-carboxymethyl chitosan (OCC) polymeric micelles modified with octreotide (OCT) and to explore the potential feasibility as doxorubicin (DOX) delivery carrier.OCT-PEG-OCC was synthesized by active ester reaction through polyethylene glycol spacer.The structure of OCT-PEG-OCC was characterized by 1 H NMR.Drug-loaded polymeric micelles were prepared by dialysis.In vitro release of DOX from OCT-PEG-OCC micelles were evaluated using a dialysis method in various buffes.MTT experiments were used to evaluate the cytotoxic effect to MCF-7 cells.It was found that octreotide was conjugated to free carboxy of OCC with polyethylene glycol as spacer successfully.Nanomicelles of OCT-PEG-OCC were self-assembled in water.OCT-PEG-OCC micelles showed excellent drug loading capacites for DOX with drug loading of 35.7% and encapsulation efficiency of 97.5%;the mean size of DOX-OCT-PEG-OCC micelles was 138.8 nm with polydisperse index of 0.184;the Zeta potential was -34.0 mV,X-ray diffraction confirmed that DOX occurs as amorphous or molecular dispersion which could solubilized in the hydrophobic core of micelles.Release behavior of DOX formulated in DOX-OCT-PEG-OCC micelles was best fitted to non-zero-order kinetics and pH-dependent.Compared with DOX-OCC micelles,DOX-OCT-PEG-OCC micelles exhibited stronger cytotoxicity to MCF-7 cells (SSTR-overexpressing) and comparble cytotoxicy to WI-38 cells (no SSTR-expressing).These results indicated active-targeting delivery in cancer therapy,which has a bright future.
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