PEG修饰鳖甲肽HGRFG脂质体的药动学研究
|
摘要
目的制备鳖甲肽HGRFG脂质体以及聚乙二醇(polyethylene glycol,PEG)修饰后的长循环脂质体,考察经修饰的脂质体较未修饰脂质体在动物体内分布及滞留情况。方法采用BLB/c裸鼠荧光活体成像实验,进行脂质体体内分布及代谢研究;采用药动学实验,初步探究2种载药脂质体在血浆内的滞留时间。结果 2种载药脂质体均能广泛分布于实验动物体内。与未经修饰的脂质体载药组相比,经PEG修饰的长循环脂质体载药组中裸鼠荧光全部消失的时间明显延长,药物在血浆滞留时间也明显延长。结论经PEG修饰后的长循环脂质体可以延长药物在实验动物体内的滞留时间,延长药物半衰期。
OBJECTIVE Trionycis Carapax Peptide HGRFG liposome and its long-circulating liposome modified by polyethylene glycol(PEG) were prepared to study the distribution of modified liposomes and unmodified liposomes in animals.METHODS The BLB/c nude mouse fluorescence in vivo imaging experiment was used to study the distribution and metabolism of liposomes in vivo. The pharmacokinetic experiments were used to investigate the retention time of two different drug-coated liposomes in plasma. RESULTS Two different drug-coated liposomes were widely distributed in experimental animals. The retention time of fluorescence disappearance in nude mice of PEG-modified long-circulating liposome-packaging group was significantly higher than that in unmodified liposome-containing drug group. The retention time of the drug in the unmodified liposome group was significantly lower than that in the PEG-modified group. CONCLUSION It has been experimentally confirmed that long-circulating liposomes modified by PEG can prolong the storage time of the drug in experimental animals and prolong the half-life of the drug.
OBJECTIVE Trionycis Carapax Peptide HGRFG liposome and its long-circulating liposome modified by polyethylene glycol(PEG) were prepared to study the distribution of modified liposomes and unmodified liposomes in animals.METHODS The BLB/c nude mouse fluorescence in vivo imaging experiment was used to study the distribution and metabolism of liposomes in vivo. The pharmacokinetic experiments were used to investigate the retention time of two different drug-coated liposomes in plasma. RESULTS Two different drug-coated liposomes were widely distributed in experimental animals. The retention time of fluorescence disappearance in nude mice of PEG-modified long-circulating liposome-packaging group was significantly higher than that in unmodified liposome-containing drug group. The retention time of the drug in the unmodified liposome group was significantly lower than that in the PEG-modified group. CONCLUSION It has been experimentally confirmed that long-circulating liposomes modified by PEG can prolong the storage time of the drug in experimental animals and prolong the half-life of the drug.
引文
[1]KRAFT J C,FREELING J P,WANG Z,et al.Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems[J].J Pharm Sci,2014,103(1):29-52.
[2]EVJEN TJ,HAGTVET E,MOUSSATOV A,et al.In vivo monitoring of liposomal release in tumours following ultrasound stimulation[J].Eur J Pharm Biopharm,2012,84(3):526-531.
[3]ALLEN T M,CULLIS P R.Liposomal drug delivery systems:From concept to clinical applications[J].Adv Drug Deliv Rev,2013,65(1):36-48.
[4]HU S J,WANG Y,QIU Y Y,et al.Targeted study of bufalin-mPEG-PLGA-PLL-cRGD on colorectal cancer in nude mice[J].J Med Res(医学研究杂志),2013,42(7):54-57.
[5]HU C L,TANG Y P.Synthesis of an active peptide from Carapax Trionycis and its inhibitory effect on the proliferation of hepatic stellate cells[J].J Chin Pharm Sci,2012,21(2):132-135.
[6]TANG H X,ZHAO T W,HUANG Y,et al.Pharmacokinetics and hepatic targeting of trionycis carapax peptide sterically stabilized liposome[J].Chin J Exp Tradit Med Form(中国实验方剂学杂志),2017,23(9):68-73.
[7]RABANEL J M,AOUN V,ELKIN I,et al.Drugloadednanocarriers:passive targeting and crossing of biological barriers[J].Curr Med Chem,2012,19(19):3070-3102.
[8]MISHRA S,WEBSTER PDAVIS M E.PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene delivery particles[J].Eur J Cell Biol,2004,83(3):97-111.
[9]HONG R L,HUANG C J,TSENG Y L,et al.Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice:is surface coating with polyethylene glycol beneficial?[J].Clin Cancer Res,1999,5(11):3645-3652.
[10]TAGAMI T,NAKAMURA K,SHIMIZU T,et al.Effect of siRNA in PEG-coated siRNA-lipoplex on anti-PEG IgMproduction.[J].J Control Release,2009,137(3):234-240.
[11]ISHIDA T,MAEDA R,ICHIHARA M,et al.Accelerated clearance of PEGylated liposomes in rats after repeated injections[J].J Control Release,2003,88(1):35-42.
[2]EVJEN TJ,HAGTVET E,MOUSSATOV A,et al.In vivo monitoring of liposomal release in tumours following ultrasound stimulation[J].Eur J Pharm Biopharm,2012,84(3):526-531.
[3]ALLEN T M,CULLIS P R.Liposomal drug delivery systems:From concept to clinical applications[J].Adv Drug Deliv Rev,2013,65(1):36-48.
[4]HU S J,WANG Y,QIU Y Y,et al.Targeted study of bufalin-mPEG-PLGA-PLL-cRGD on colorectal cancer in nude mice[J].J Med Res(医学研究杂志),2013,42(7):54-57.
[5]HU C L,TANG Y P.Synthesis of an active peptide from Carapax Trionycis and its inhibitory effect on the proliferation of hepatic stellate cells[J].J Chin Pharm Sci,2012,21(2):132-135.
[6]TANG H X,ZHAO T W,HUANG Y,et al.Pharmacokinetics and hepatic targeting of trionycis carapax peptide sterically stabilized liposome[J].Chin J Exp Tradit Med Form(中国实验方剂学杂志),2017,23(9):68-73.
[7]RABANEL J M,AOUN V,ELKIN I,et al.Drugloadednanocarriers:passive targeting and crossing of biological barriers[J].Curr Med Chem,2012,19(19):3070-3102.
[8]MISHRA S,WEBSTER PDAVIS M E.PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene delivery particles[J].Eur J Cell Biol,2004,83(3):97-111.
[9]HONG R L,HUANG C J,TSENG Y L,et al.Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice:is surface coating with polyethylene glycol beneficial?[J].Clin Cancer Res,1999,5(11):3645-3652.
[10]TAGAMI T,NAKAMURA K,SHIMIZU T,et al.Effect of siRNA in PEG-coated siRNA-lipoplex on anti-PEG IgMproduction.[J].J Control Release,2009,137(3):234-240.
[11]ISHIDA T,MAEDA R,ICHIHARA M,et al.Accelerated clearance of PEGylated liposomes in rats after repeated injections[J].J Control Release,2003,88(1):35-42.