Preparation and in Vitro Evaluation of Redox-responsive Nano-drug Delivery System of Poly-salicylic Acid

OBJECTIVE To connect poly-salicylic acid(PSA) to carboxymethyl chitosan to form self-assembled nanoparticles(NPs), and conduct characterization and in vitro evaluation. METHODS O-carboxymethyl chitosan(OCMC) was used as a hydrophilic bone chain to connect PSA to carboxymethyl chitosan through disulfide bond. The structure of the copolymer was confirmed by ¹H-NMR and IR. Self assembled NPs were prepared by ultrasonic method, and their particle size and Zeta potential were characterized. The critical aggregation concentration(CAC) of NPs was determined by pyrene fluorescence probe method. The encapsulation efficiency and drug loading of DOX loaded NPs were determined. MTT assay was used to investigate the anti-tumor activity of drug loaded NPs in vitro. RESULTS The particle size of OCMC disulfide bonded poly-salicylic acid NPs(OCMC-SS-PSA NPs) was (148.5±2.3)nm; CAC value was (0.069 3±0.001 3)mg·mL^-1; its reduction sensitivity and pH sensitivity was good. The particle size of DOX/OCMC-SS-PSA NPs was (160.5±1.7)nm, the drug loading was (17.43±0.56)%, and the encapsulation efficiency was (89.67±1.23)%. MTT test showed that OCMC-SS-PSA NPs had good biological safety; the cell uptake experiment showed that DOX/OCMC-SS-PSA NPs stayed longer in the cells. CONCLUSION OCMC-SS-PSA NPs have small particle size, good reduction responsiveness, pH sensitivity and biosafety. OCMC-SS-PSA NPs can be used as a new nano drug delivery system with both reduction response and pH sensitivity.