Zwitterionic alginate derivative as a new delivery platform for enhanced blood circulation.

Purpose: Poly(ethylene glycol) (PEG), a synthetic polymer known for its hydrophilicity and biocompatibility, has long been used in drug delivery systems to prevent non-specific protein adsorption and to extend the blood circulation time of drug carriers and protein drugs. However, PEG has several drawbacks including poor stability, accumulated toxicity, and immunogenicity induced by repeated injections. Recently, zwitterionic polymers, known for their super-hydrophilic and antifouling properties, have been considered excellent alternatives to PEG. In this study, we synthesized a new zwitterionic polymer from biocompatible sodium alginate and lysine.

Methods: Sodium alginate (Alg) was conjugated with lysine (Lys) using the EDC/sulfo-NHS chemistry to form a zwitterionic alginate derivative (Alg-Lys). The biocompatibility was evaluated using in vitro cellular assays and in vivo animal studies. After further conjugation of zwitterionic near-infrared (NIR) fluorescent dye ZW800, an in vivo NIR fluorescence imaging study was conducted to evaluate the ability of Alg-Lys to enhance blood circulation time.

Results: Characterization of Alg-Lys showed that the carboxylic acid groups in Alg were completely replaced by Lys molecules. No cytotoxic effects were observed in the in vitro cytotoxicity tests of Alg-Lys-treated cancer cells and normal cells. Serum biochemical analysis confirmed the biocompatibility of Alg-Lys. ZW800-conjugated Alg-Lys exhibited strong fluorescence signals throughout the body 24 h after intravenous injection, whereas ZW800-conjugated Alg was rapidly removed from the body.

Conclusion: The zwitterionic alginate derivative showed potential utility as a new delivery platform for imaging agents and drugs.