摘要
以A型明胶为原料、5-氟尿嘧啶为模型药物、异丙醇为凝聚剂,采用单凝聚法制备了5-氟尿嘧啶/明胶纳米载药颗粒(5-FU/GNPs),并测定了纳米颗粒的粒径分布、载药量、体外缓释效果和抗肿瘤性能。结果表明:5-FU/GNPs表面形态良好,分散均一,平均粒径为(75.1±2.1)nm,载药量为23.5%±1.9%;5-FU/GNPs具有良好的缓释性能,Higuchi方程对微球的体外药物释放情况拟合度较高。四甲基偶氮唑蓝实验表明:5-FU/GNPs对胃癌细胞(SGC7901)的抑制率可达71%。
5-Fluorouracil/gelatin nanoparticles(5-FU/GNPs) were prepared by simple coacervation method using type A gelatin as raw material,5-fluorouracil as entrapped pharmaceutical,isopropanol as coacervation reagent. The particle size distribution,drug loading,in vitro drug release and antitumor activities of 5-FU/GNPs were investigated. The results showed that 5-FU/GNPs had excellent surface morphology,and dispersed uniformly with an average particle size of(75.1±2.1) nm. The average drug loading was about 23.5%±1.9%. In vitro release experiments displayed that 5-FU/GNPs exhibited good release performance,the release of 5-fluorouracil from 5-FU/GNPs accorded with the Higuchi equation,indicating that the gelatin could sustain the release of 5-fluorouracil. MTT measurement showed that 5-FU/GNPs had significant cytotoxicity on human gastric cancer cells(SGC7901). Thus,the prepared 5-FU/GNPs could be used as a kind of drug-loading carrier in pharmaceutical field.
引文
[1]Joanna D,Rola M,Ana Q,et al.Preparation,characterization and application in controlled release of ibuprofen-loaded guar gum/montmorillonite bionanocomposites[J].Applied Clay Science,2017,135:52-63.
[2]Gao Di(高迪),Fan Ye(樊晔),Fang Yun(方云),et al.Preparation and drug release properties of the self-crosslinked conjugated linoleic acid ufasomes by thermal polymerization[J].Fine Chemicals(精细化工),2016,33(5):509-513.
[3]Ye L,Jiang T,Shao H Z,et al.Mi R-1290 is a biomarker in DNA-mismatch-repair-deficient colon cancer and promotes resistance to 5-fluorouracil by directly targeting h MSH2[J].Molecular Therapy Nucleic Acids,2017,7:453-464.
[4]Li Y H,Lei F,Niu Y B,et al.An apple oligogalactan enhances the growth inhibitory effect of 5-fluorouracil on colorectal cancer[J].European Journal of Pharmacology,2017,804:13-20.
[5]Joanna L W,Julia A S,Moniyka S,et al.5-Fluorouracil for actinic keratosis treatment and chemoprevention:A randomized controlled trial[J].Journal of Investigative Dermatology,2017,137(6):1367-1370.
[6]Elzoghby A O.Gelatin-based nanoparticles as drug and gene delivery systems:reviewing three decades of research[J].Journal of Controlled Release,2013,172(3):1075-1091.
[7]Kenneth O,Gerhard W,Gert F,et al.Matrix-loaded biodegradable gelatin nanoparticles as new approach to improve drug loading and delivery[J].European Journal of Pharmaceutics and Biopharmaceutics,2010,76(1):1-9.
[8]Liu Tianqing(刘天晴),Song Lina(宋丽娜).Preparation and properties of Fe OOH-gelatin complex nano-particles[J].ACTA Chimica Sinica(化学学报),2010,68(11):1057-1062.
[9]Manoj N,Pharm M,Dinesh M,et al.Development,characterization,and toxicity evaluation of amphotericin B–loaded gelatin nanoparticles[J].Nanomedicine:Nanotechnology,Biology,and Medicine,2008,4(3):252-261.
[10]Won Y W,Yoon S M,Sonn C H,et al.Nano self-assembly of recombinant human gelatin conjugated with R-Tocopheryl succinate for Hsp90 inhibitor,17-AAG,Delivery[J].ASC Nano,2011,5(5):3839-3848.
[11]Luo Donghui(骆东辉),Liu Anni(刘安妮),Li Mingfang(李明芳),et al.Preparation and bio-evaluation of iodine labelling gelatin microspheres and the coating microspheres with sodium alginate[J].Chemical Journal of Chinese Universitise(高等学校化学学报),2011,32(6):1412-1417.
[12]Katsuya O,Takahiro K,Tetsuya O,et al.One-step preparation of rifampicin/poly(lactic-co-glycolic acid)nanoparticle-containing mannitol microspheres using a four-fluid nozzle spray drier for inhalation therapy of tuberculosis[J].Journal of Controlled Release,2009,135(1):19-24.