pH-sensitive Nanoparticles for High Loading and Efficient Delivery of Doxorubicin

Abstract

An acid-sensitive delivery system based on acylhydrazone bond was developed for high loading and efficient delivery of doxorubicin. Doxorubicin(DOX) was covalently combined with dihydrazide adipate to form acid-sensitive hydrazone bond based on Schiff base reaction, then the intermediate was covalently combined with carboxymethyl chitosan through amide bond to form polymeric prodrugs, and nanoparticles were formed through self-assembling. Moreover, the structural and particle properties of CMCS-ADH-DOX were characterized by ultraviolet visible near infrared spectrophotometry (UV), nuclear magnetic resonance spectroscopy (¹H-NMR), fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The mean diameter of the self-assembled nanoparticles is 165 nm, while the morphology is a relatively uniform spherical shape. Moreover, these DOX-loaded nanoparticles showed pH-triggered drug release behavior. Compared with free DOX, CAD NPs showed lower toxic side effects in L929 cells and similar toxicity in 4T1 cells. The experimental results indicate that the CMCS-ADH-DOX nanoparticles may be used as an acid-sensitive targeted delivery system with good application prospect for cancer.

Keywords

nanoparticles / acylhydrazone bond / polymeric prodrug / acid-sensitive