Chitosan-coated nanodiamonds: Mucoadhesive platform for intravesical delivery of doxorubicin

Nanodiamonds (NDs) are an emerging delivery system with a massive surface area qualifying them for efficient loading with various drugs. However, NDs easily scavenge ions upon mixing with physiological media leading to rapid aggregation. Herein, chitosan was employed to endue steric stabilization to NDs and confer adhesiveness to the particles improving their retention in the urinary bladder. The effect of chitosan molecular weight and pH on the particle size and surface charge of chitosan-coated doxorubicin-loaded NDs (Chi-NDX) was investigated. Selected formula exhibited high drug loading efficiency (>90 %), small particle size (<150 nm), good colloidal stability, acid-favored drug release but limited stability in cell culture media. After further stabilization with TPP or dextran sulfate, selected TPP-treated formula displayed more potent cytotoxic effect compared with free doxorubicin and uncoated nanoparticles, and higher drug retention in ex vivo bovine bladder. Therefore, TPP-Chi-NDX is suggested as a promising system for mucosal anticancer delivery.