Dextran-based nanoparticles with 5-FU-conjugated polymethacrylate segments for drug delivery: Synthesis of amphiphilic graft copolymers by mechanochemical solid-state polymerization and characterization

被引:1
作者
Doi, Naoki [1 ]
Yamauchi, Yukinori [2 ]
Sasai, Yasushi [3 ]
Suzuki, Kaho [1 ]
Kuzuya, Masayuki [1 ]
Kondo, Shin-ichi [1 ]
机构
[1] Gifu Pharmaceut Univ, Lab Pharmaceut Phys Chem, 1-25-4 Daigaku Nishi, Gifu 5011196, Japan
[2] Matsuyama Univ, Coll Pharmaceut Sci, Dept Pharmaceut Phys Chem, 4-2 Bunkyo Cho, Matsuyama, Ehime 7908578, Japan
[3] Gifu Univ Med Sci, Fac Pharm, 4-3-3 Nijigaoka, Kani, Gifu 5090293, Japan
关键词
Dextran; Graft copolymer; Drug delivery; Cancer; Drug release; Solid-state polymerization; MACROMOLECULAR THERAPEUTICS; CHITOSAN; POLYSACCHARIDES; MECHANISM; RELEASE; MECHANOLYSIS; ACCUMULATION; PRODRUGS; GENE;
D O I
10.1016/j.ijbiomac.2024.132950
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dextran (Dx) is a biodegradable and biocompatible polysaccharide, thus promising as a drug delivery carrier for tumor therapy. Herein, we applied mechanical energy to a high molecular weight Dx to control its molecular weight and simultaneously generate mechanoradicals. The solid-state polymerization of methacrylate- or methacrylamide derivatives initiated with Dx mechanoradicals showed polymer conversion of >95%, yielding Dx-based graft copolymers with molecular weights of approximately 30,000 g mol(-1). The Dx-based graft copolymers with hydrophobic segments formed nanoparticles with a particle size of 25-35 nm in an aqueous solution. The anti-pancreatic tumor drug 5-fluorouracil (5-FU) was covalently conjugated onto the hydrophobic segments of the amphiphilic Dx, and the nanoparticles were also prepared. The drug release profile from 5-FU-conjugated nanoparticles corresponded well to the Korsmeyer-Peppas model applied to drug release from matrix substrates, and was also immensely predicted by the Logistic and Gompertz curves. The 5-FU-conjugated nanoparticles showed cytotoxicity against the pancreatic adenocarcinoma cell lines (BxPC-3) that were not significantly inferior to the 5-FU positive group. Furthermore, the fluorescein-labeled nanoparticles internalized into BxPC-3 within 6 h and actively migrated into the cytosol. These results suggest that Dx-based graft copolymers with hydrophobic segments might be used to enhance therapeutic activity.
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页数:14
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