靶向羧甲基壳聚糖-熊果酸纳米药物载体的制备及表征
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摘要
将叶酸(FA)和氧-羧甲基壳聚糖(OCMCS)通过化学键连接制成叶酸-羧甲基壳聚糖聚合物,再偶联上熊果酸(UA)得到叶酸-羧甲基壳聚糖-熊果酸聚合物(FA-OCMCS-UA),并通过自组装包裹另一种抗癌药物10-羟基喜树碱(HCPT),形成叶酸-羧甲基壳聚糖-熊果酸/10-羟基喜树碱纳米药物粒子(FA-OCMCS-UA/HCPT)。采用1 HNMR和FT-IR对FA-OCMCS-UA进行结构表征;TEM观察FA-OCMCS-UA/HCPT NPs的形状。结果表明,1 HNMR和FT-IR证实了FA和UA成功偶联到OCMCS上。TEM显示FA-OCMCS-UA/HCPT纳米粒子呈球形,粒径为200～300nm。
Folic acid(FA)and carboxymethyl chitosan(OCMCS)were coupled by amide bonds to form a folic acid-carboxymethyl chitosan polymer,and then linked with ursolic acid(UA)to form a folic acid-carboxymethyl chitosan-ursolic acid conjugate(FA-OCMCS-UA). The 10-hydroxycamptothecin was self-assembled bynanoprecipitation to form folic acid-carboxymethyl chitosan-ursolicacid/10-hydroxycamptothe-cinna noparticles(FA-OCMCS-UA/HCPT).FA-OCMCS-UA structural was characterized by 1 HNMR and FT-IR; The morphology of FA-OCMCS-UA/HCPT nanoparticles was observed by transmission electron microscope.The results showed that folic acid and ursolic acid was successfully interacted with carboxymethyl chitosan by 1 HNMR and FT-IR spectra.Transmission electron microscopy showed that the FA-OCMCS-UA/HCPT nanoparticles were spherical and the particle size was 200～300 nm.
Folic acid(FA)and carboxymethyl chitosan(OCMCS)were coupled by amide bonds to form a folic acid-carboxymethyl chitosan polymer,and then linked with ursolic acid(UA)to form a folic acid-carboxymethyl chitosan-ursolic acid conjugate(FA-OCMCS-UA). The 10-hydroxycamptothecin was self-assembled bynanoprecipitation to form folic acid-carboxymethyl chitosan-ursolicacid/10-hydroxycamptothe-cinna noparticles(FA-OCMCS-UA/HCPT).FA-OCMCS-UA structural was characterized by 1 HNMR and FT-IR; The morphology of FA-OCMCS-UA/HCPT nanoparticles was observed by transmission electron microscope.The results showed that folic acid and ursolic acid was successfully interacted with carboxymethyl chitosan by 1 HNMR and FT-IR spectra.Transmission electron microscopy showed that the FA-OCMCS-UA/HCPT nanoparticles were spherical and the particle size was 200～300 nm.
引文
[1]Manchun S,Dass C R,Sriamornsak P.Targeted therapy for cancer using pH-responsive nanocarrier systems[J].Life Sciences,2012,90(11-12):381-387.
[2]Chan A,Orme R P,Fricker R A,et al.Remote and local control ofstimuli responsive materials for therapeutic applications[J].Advanced Drug Delivery Reviews,2013,65(4):497-514.
[3]Pulkkinen M,Pikkarainen J,Wirth T,et al.Three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology:formulation development and in vitro anticancer activity[J].European Journal of Pharmaceutics&Biopharmaceutics,2008,70(1):66-74.
[4]Morrow C S,Smitherman P K,Townsend A J.Role of multidrug-resistance protein in glutathione S-transferase P1·-1-mediated resistance to 4-nitroquinoline 1-oxide toxicities in HepG2cells[J].Mol Carcinog,2000,29(3):170-178.
[5]Wang L C,Chen X G,Liu C S,et al.Dissociation behaviors of carboxyl and amine groups carboxymethyl-chitosan in aqueous system[J].J Polym Sci Part B:Polym Phys,2008,46(14):1419-1429.
[6]Kong L,Li S,Liao Q,et al.Oleanolic acid and ursolic acid:novel hepatitis C virus antivirals that inhibit NS5Bactivity[J].Antiviral Res,2013,98(1):44-53.
[7]Zang L L,Wu B N,Lin Y,et al.Research progress of ursolic acid’s anti-tumor actions[J].Chin J Integr Med,2014,20(1):72-79.
[8]Lepeltier E,Bourgaux C,Couvreur P.Nanoprecipitation and the“ouzo effect”:application to drug delivery devices[J].Adv Drug Deliver Rev,2014,71:86-97.
[9]Schroeder J E,Shweky I,Shmeeda H,et al.Folate-mediated tumor cell uptake of quantum dots entrapped in lipid nanoparticles[J].Journal of Controlled Release,2007,124(1-2):28-34.
[10]荣利.肝靶向半乳糖化棕桐酞壳聚糖聚合物胶束作为药物载体的研究[D].广州:广东药学院,2011.
[11]何嫄.新型壳聚糖衍生物的制备及其自组装研究[D].杭州:浙江大学,2010.
[12]Fang J,Liao L,Yin H Z,et al.Enhanced bacterial tumor delivery by modulating the EPR effect and therapeutic potential of lactobacillus casei[J].Journal of Pharmaceutical Sciences,2014,103(10):3235-3243.
[2]Chan A,Orme R P,Fricker R A,et al.Remote and local control ofstimuli responsive materials for therapeutic applications[J].Advanced Drug Delivery Reviews,2013,65(4):497-514.
[3]Pulkkinen M,Pikkarainen J,Wirth T,et al.Three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology:formulation development and in vitro anticancer activity[J].European Journal of Pharmaceutics&Biopharmaceutics,2008,70(1):66-74.
[4]Morrow C S,Smitherman P K,Townsend A J.Role of multidrug-resistance protein in glutathione S-transferase P1·-1-mediated resistance to 4-nitroquinoline 1-oxide toxicities in HepG2cells[J].Mol Carcinog,2000,29(3):170-178.
[5]Wang L C,Chen X G,Liu C S,et al.Dissociation behaviors of carboxyl and amine groups carboxymethyl-chitosan in aqueous system[J].J Polym Sci Part B:Polym Phys,2008,46(14):1419-1429.
[6]Kong L,Li S,Liao Q,et al.Oleanolic acid and ursolic acid:novel hepatitis C virus antivirals that inhibit NS5Bactivity[J].Antiviral Res,2013,98(1):44-53.
[7]Zang L L,Wu B N,Lin Y,et al.Research progress of ursolic acid’s anti-tumor actions[J].Chin J Integr Med,2014,20(1):72-79.
[8]Lepeltier E,Bourgaux C,Couvreur P.Nanoprecipitation and the“ouzo effect”:application to drug delivery devices[J].Adv Drug Deliver Rev,2014,71:86-97.
[9]Schroeder J E,Shweky I,Shmeeda H,et al.Folate-mediated tumor cell uptake of quantum dots entrapped in lipid nanoparticles[J].Journal of Controlled Release,2007,124(1-2):28-34.
[10]荣利.肝靶向半乳糖化棕桐酞壳聚糖聚合物胶束作为药物载体的研究[D].广州:广东药学院,2011.
[11]何嫄.新型壳聚糖衍生物的制备及其自组装研究[D].杭州:浙江大学,2010.
[12]Fang J,Liao L,Yin H Z,et al.Enhanced bacterial tumor delivery by modulating the EPR effect and therapeutic potential of lactobacillus casei[J].Journal of Pharmaceutical Sciences,2014,103(10):3235-3243.