Ethylene glycol oligomer modified-sodium alginate for efficiently improving the drug loading and the tumor...

The high viscosity of sodium alginate (ALG) causes its insufficient drug loading and limits its application as a drug carrier. In the present work, we synthesized poly(ethylene glycol) oligomer (mOEG)-modified sodium alginate (ALG-mOEG) and characterized its properties as a drug delivery system. Our results showed that ALG-mOEG displayed a greatly reduced viscosity (0.024 Pa s at 2.0 wt%) with a significantly improved drug loading capacity (18.0% (w/w)) compared with unmodified ALG (6.9% (w/w)). In addition, DOX-ALG-mOEG nanoparticles (DOX-ALG-mOEG NPs) with high drug loading were more cytotoxic for HepG2 cells in vitro and showed a higher antitumor activity in vivo compared with the control group (DOX-ALG NPs) at the same dose of DOX. DOX-ALG-mOEG NPs inhibited HepG2 proliferation in vitro with an IC₅₀ value of 220.0 ng mL^-1 and reduced tumor growth in vivo by 75.6%, while DOX-ALG NPs showed activities of 443.9 ng mL^-1 and 62.7%, respectively. Meanwhile, we did not observe the "accelerated blood clearance (ABC)" phenomenon in these mOEG-modified ALG nanoparticles. In view of most biologic and chemical molecules used for the biological function being hydrophobic, we thought the ALG-mOEG scaffold also might serve as an efficient long-duration carrier for other hydrophobic molecules with minimal immunogenicity.