A pH-Sensitive Nanosystem Based on Carboxymethyl Chitosan for Tumor-Targeted Delivery of Daunorubicin
Nanoparticles, such as polymeric micelles, are currently regarded as effective drug delivery vehicles. In this study, a series of carboxymethyl chitosan/daunorubicin (CMCS/DNR) conjugates with macromolecular carriers of different molecular weights (MWs) were prepared and structurally characterized by Fourier transform infrared spectroscopy (FT-IR) and 1H-NMR spectroscopy. The results indicated that the MWs of the carriers greatly influenced the drug loading capacity. DNR was conjugated to the polymer via an acid-sensitive hydrazone linkage susceptible to hydrolysis at pH 5–6, thereby enabling intracellular DNR release. In aqueous media, the conjugates spontaneously formed nano-sized particles with core–shell structures (CMCS and DNR as the shell and core, respectively). Dynamic light scattering (DLS) and trans-mission electron microscopy (TEM) indicated that the prepared nanoparticles were spherical in shape with diameters of 100–200 nm and had a slight negative surface charge. In addition, in vitro drug release studies demonstrated that the micelles were highly sensitive to mild acidic conditions (pH 5.0) but remained reasonably stable at pH 6.5 and pH 7.4. Importantly, cell counting kit-8 (CCK-8) assays demonstrated that DNR-conjugated nanoparticles exerted a cytotoxic effect on HeLa cells, with the IC50 being approximately 2 times higher than that of free-DNR. Furthermore, confocal laser scanning microscopy (CLSM) revealed that the CMCS-hyd-DNR nanosystem could efficiently deliver and release DNR in the nuclei of cancer cells. Taken together, the developed CMCS based pH-sensitive nanosystem may be a potential drug delivery vehicle for cancer therapy.
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Document Type: Research Article
Publication date: August 1, 2016
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