In order to decrease the toxicity of paclitaxel (PTX) and increase the efficiency, we developed an amphiphilic PTX injection system using a biodegradable and biocompatible polymer synthesized by folic acid, cholesterol, and chitosan (FACC). This FACC-based polymer had a low critical concentration (64.13μg/ml) and could self-assemble in aqueous condition to form nanoscale micelles. The particle sizes of FACC-PTX micelles were 253.2±0.56 nm, the encapsulation efficiency and loading capacity of these FACC-PTX micelles were 65.1±0.23% and 9.1±0.16%, respectively. The cumulative release rate was about 85% at pH 5.0 which was higher than that at pH 7.4 (76%). This pH-dependent release behavior was highly suggesting that PTX release from FACC-PTX micelles might be higher in a weak acidic tumor microenvironment and lower toxic for normal cells. The anti-cancer effectiveness of FACC-PTX micelles was investigated by in vitro cytotoxicity and targeting study. The results revealed that FACC micelles have non-toxic on cells as evidenced by high cell viability found (86% to 100%) in the cells cultured with various concentrations of FACC micelles (1 to 500 μg/ml). Targeting study indicated that the cytotoxic efficacy of FACC-PTX micelles was significantly higher than that with Taxol® in the Hela cells (folate receptor-positive cells). These findings indicated that the anticancer efficiency of PTX can be enhanced by adding some cancer cell positive receptor into drug carrier and the FACC micelle was a potential tumor targeting carrier for PXT delivery.
Nanoparticles are attractive in medicine because their surfaces can be chemically modified for targeting specific disease cells, especially for cancer. Providing an in-vivo like platform is crucial to evaluate the biological behaviours of nanoparticles. This paper presents a microfluidic device that could culture two cell lines in parallel in in-vivo like fluidic microenvironments and be used for testing the tumor targeting of folic acidcholesterolchitosan (FACC) nanoparticles. The uniformity and uniformity of flow fields inside the cell culture units are investigated using the finite element method and particle tracking technology. Hela and A549 cells are cultured in the microfluidic chip under continuous media supplementation, mimicking the fluid microenvironment in vivo. Cell introducing processes are presented by the flow behaviours of inks with different colours. The two cell lines are identified by detecting folate receptors on the cellular membranes. The growth curves of the two cell lines are measured. The two cell lines cultured paralleled inside the microfluidic device are treated with FITC-FACC to investigate the targeting of FACC. The tumor targeting of FACC are also detected by in vivo imaging of Hela cells growth in nude mice models. The results indicate that the microfluidic device could provide a dynamic, uniform and stable fluidic microenvironment to test the tumor targeting of FACC nanoparticles.
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