Chitosan Oligosaccharide/Salicylic Acid Nanoparticles for Doxorubicin Delivery

ABSTRACT: OBJECTIVE To investigate the probability of Chitosan oligosaccharide (CSO)/Salicylic acid (SA) nanoparticles to encapsulate alkalized doxorubicin and to evaluate the physicochemical properties and in vitro profile of drug delivery system. METHODS CSO/SA conjugates were synthesized by a reaction between amino-groups of CSO and carboxyl groups of SA using 1-ethyl-3-(3-dimethyla-minopropyl) carbodiimide as a coupling agent. The amino substitution degree (SD%) of CSO/SA was determined by a 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) test as reported before. The CSO/SA blank nanoparticles were prepared by ultrasonic dispersion method. The critical aggregation concentration of nanoparticles was obtained by the fluorescence pyrene study. Dynamic light scattering method was used to determine the size and zeta potential of nanoparticles. MTT assay was used to evaluate the cytotoxicity of nanoparticles. Alkalizated doxorubicin was used as the model drug, drug-loaded CSO/SA nanoparticles were prepared by dialysis method. RESULTS The amino substitution degree of CSOMW=9000/salicylic acidtheory fed amount%=50% was 16.92%, and the critical aggregation concentration of blanked nanoparticles was 867.0 μg/mL. The particle size and zeta potential of blank nanoparticles were 434.0 nm and 48.6 mV separately; the IC50 of the nanoparticles on cell Hep-G2 was 1745μg/mL. The drug content of nanoparticles was 8.52% and the loading efficiency was 93.15% when the amount of drug fed was 10%，the particle size and zeta potential of drug-loaded nanoparticles were 214.2 nm and 33.6 mV separately. In vitro release results illustrated that drug-loading nanoparticles had pH sensitivity，and the drugs were released mostly in the way of erosion. CONCLUSION CSO/SA could encapsulate alkalized doxorubicin to form uniform, sustained drug delivery nanoparticles. The drug-loaded nanoparticles presented pH-dependent property. CSO/SA nanoparticles may be a potential candidate to be a drug carrier material.