Zwitterionic alginate derivative as a new delivery platform for enhanced blood circulation
Zwitterionic alginate derivative as a new delivery platform for enhanced blood circulation
Lee Hyeri(Devision of Technology Convergence, National Cancer Center); Li Yan(Devision of Technology Convergence, National Cancer Center); Bao Kai(Department of Radiology, Massachusetts General Hospital and Harvard Medical School, USA); Lee Seon Sook(Devision of Technology Convergence, National Cancer Center); Kang Homan(Department of Radiology, Massachusetts General Hospital and Harvard Medical School, USA); Choi Hak Soo(Massachusetts General Hospital and Harvard Medical School); Choi Yongdoo(Division of Technology Convergence, National Cancer Center)
55권 1호, 143~154쪽
초록
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.
Abstract
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.
- 발행기관:
- 한국약제학회
- 분류:
- 약학