5-Fluorouracil-loaded Self-assembled pH-sensitive Nanoparticles as Novel Drug Carrier for Treatment of Malignant Tumors

Abstract

Abstract: In order to improve the cancer-targeting and selective activity of antineoplastic agent [5-fluorouracil (5-FU)], a novel pH-responsive drug delivery system [pullulan acetate/sulfonamide (PA/SDM) conjugate] was synthesized by a diafiltration method. Sulfonamide was grafted to the hydrophobically modified pullulan acetate to enhance the pH sensitivity for better cancer-targeting delivery. 5-FU was loaded into the self-assembled nanoparticles by the same method. The drug-loaded self-assembled nanoparticles were successfully obtained and characterized in terms of particle size, morphology and drug loading and release profile at various pHs. The results showed that the mean diameter of the self-assembled particles was approximately 100nm, with uniform size and good spherical morphology. The nanoparticles showed good stability at pH 7.4, which is equal to that of the normal body fluid, but shrank and aggregated below pH 6.8, which is close to the pH with tumors. The loading efficiency and concentration of released 5-FU was monitored at 269 nm on the UV/Vis spectrophotometer. The release profile was heavily pH-dependent around physiological pH, and the release rate was significantly enhanced under pH of 6.8.

Key words: 5-fluorouracil, self-assembled nanoparticles, pH sensitivity, drug delivery, pullulan

摘要： In order to improve the cancer-targeting and selective activity of antineoplastic agent [5-fluorouracil (5-FU)], a novel pH-responsive drug delivery system [pullulan acetate/sulfonamide (PA/SDM) conjugate] was synthesized by a diafiltration method. Sulfonamide was grafted to the hydrophobically modified pullulan acetate to enhance the pH sensitivity for better cancer-targeting delivery. 5-FU was loaded into the self-assembled nanoparticles by the same method. The drug-loaded self-assembled nanoparticles were successfully obtained and characterized in terms of particle size, morphology and drug loading and release profile at various pHs. The results showed that the mean diameter of the self-assembled particles was approximately 100nm, with uniform size and good spherical morphology. The nanoparticles showed good stability at pH 7.4, which is equal to that of the normal body fluid, but shrank and aggregated below pH 6.8, which is close to the pH with tumors. The loading efficiency and concentration of released 5-FU was monitored at 269 nm on the UV/Vis spectrophotometer. The release profile was heavily pH-dependent around physiological pH, and the release rate was significantly enhanced under pH of 6.8.

关键词: 5-fluorouracil;self-assembled nanoparticles;pH sensitivity;drug delivery;pullulan

LIULiang, JINPing, CHENGMing, ZHANGGuoliang, ZHANGFengbao. 5-Fluorouracil-loaded Self-assembled pH-sensitive Nanoparticles as Novel Drug Carrier for Treatment of Malignant Tumors[J]. .

刘亮, 晋平, 程明, 张国亮, 张凤宝. 载5-氟尿嘧啶的pH敏感自组装纳米粒制备及体外释放[J]. CIESC Journal.

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5-Fluorouracil-loaded Self-assembled pH-sensitive Nanoparticles as Novel Drug Carrier for Treatment of Malignant Tumors

载5-氟尿嘧啶的pH敏感自组装纳米粒制备及体外释放

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