Study On A Novel Amphiphilic Chitosan Derivatives Nano Drug Delivery System

Anti-tumor target-oriented drug delivery system (ATDDS) is becoming a hot point foranti-tumor research because of the advantage of orientation, enrichment, controlled release, andso on. With the development of biomedical technology and material science, the contents ofATDDS have been greatly enriched. All kinds of anti-tumor targeted preparations and therapiesare created by many scholars at home and abroad. With the recent development of nanoparticledrug-delivery systems, more attentions have been focused on polymeric micelles due to theirremarkable advantages as drug carriers. These lie in their unique characteristics, such as lowcritical micelle concentration, nanoscale size and unique core-shell architecture.In this study we prepared a novel amphiphilic polymer using a convenient scheme. Chitosanwas first modified hydrophobically with deoxycholic acid and then with polyethylene glycol toobtain a novel amphiphilic polymer. Then folic acid was covalently bound to the amphiphilicpolymer to develop a new potential cancer-targeting drug-delivery system. The structure of theconjugates was characterized using Fourier transform infrared and1H nuclear magneticresonance spectroscopy and X-ray diffraction. Based on self-aggregation, the conjugates formednanoparticles with a low critical aggregation concentration of0.035mg/ml. The mean diameterand Zeta potential of the blank nanoparticles were220nm and21mV, respectively. The blanknanoparticles maintained stable structure for one week when stored in PBS (pH=7.4) at roomtemperature. Using a membrane dialysis method, the anti-cancer drug doxorubicin (DOX) wasencapsulated into the nanoparticles with a drug-loading capacity of30.2wt%anddrug-encapsulation efficiency of62.7%. The mean diameter of the DOX-loaded nanoparticleswas about250nm, with a narrow size distribution. Transmission electron microscopy imagesshowed that the DOX-loaded nanoparticles were spherical. The in vitro drug release was studied under different conditions and the results showed that DOX was released slowly fromDOX-loaded nanoparticles without burst release. The cytotoxicity of the DOX-loadednanoparticles to HeLa cells was evaluated by MTT assay. The MTT results showed that blanknanoparticles did not show cytotoxicity even at high concentration. However, when DOX wasloaded in polymeric nanoparticles, the cell viability decreased from almost100%to less than30%as the DOX concentration increased from0.1to40μg/ml, while the cell viability decreasedto about9%when free DOX with the same concentration was used. The results of celluar uptakeby HeLa and RAW264.7cells demonstrated the tumor targeting and stealth performance of thenovel amphiphilic chitosan derivatives nanocarriers.