本文關(guān)鍵詞：高分子藥物學(xué)的研究進(jìn)展與期盼，，由筆耕文化傳播整理發(fā)布。

全文: (4097 KB)   (1 KB) 
輸出: BibTeX | EndNote (RIS)      

摘要 自從20世紀(jì)70年代提出高分子前藥的概念以來(lái),伴隨著納米技術(shù)的發(fā)展,"高分子藥物學(xué)"作為高分子科學(xué)和材料學(xué)、納米科學(xué)、藥物學(xué)、臨床醫(yī)學(xué)、分析科學(xué)的交叉學(xué)科,正在悄然形成.本文綜述了近年高分子藥物在藥物化學(xué)、制劑學(xué)、藥效學(xué)等方面所取得的進(jìn)展,概述了高分子藥物的藥理學(xué)和藥代動(dòng)力學(xué)與小分子藥物的區(qū)別與聯(lián)系,指出了高分子藥物藥效學(xué)、藥理學(xué)和藥代動(dòng)力學(xué)研究中的難題和瓶頸,特別是高分子藥物可能存在的"三種狀態(tài)"及從"納米顆粒藥"到"單個(gè)高分子藥"再到"小分子藥"的轉(zhuǎn)變,分析了高分子藥輸送過(guò)程中存在的多重屏障如毛細(xì)血管壁、細(xì)胞外基質(zhì)和細(xì)胞壁等,闡述了高分子藥物的"生理靶向"和"EPR"效應(yīng)的競(jìng)爭(zhēng),指出了高分子藥在靶向輸送和逆轉(zhuǎn)耐藥方面的優(yōu)勢(shì),強(qiáng)調(diào)了發(fā)展相關(guān)分析方法的必要性,期盼高分子科學(xué)家與藥物學(xué)家進(jìn)行真誠(chéng)有效的合作,大力促進(jìn)我國(guó)高分子藥物學(xué)和高分子藥物產(chǎn)業(yè)的創(chuàng)新和發(fā)展.

服務(wù)

E-mail Alert

RSS

收稿日期: 2013-01-04     

基金資助:

國(guó)家自然科學(xué)基金項(xiàng)目(基金號(hào)21004062, 51103148)和國(guó)家重點(diǎn)基礎(chǔ)研究發(fā)展計(jì)劃(973計(jì)劃,項(xiàng)目號(hào) 2009CB930102).

通訊作者: 景遐斌   

引用本文:   

胡秀麗, 謝志剛, 黃宇彬, 景遐斌. 高分子藥物學(xué)的研究進(jìn)展與期盼[J]. Acta Polymerica Sinica, 2013, (6): 733-749.
Xiu-li Hu, Zhi-gang Xie, Yu-bin Huang, Xia-bin Jing. THE PROGRESS AND EXPECTATION OF POLYMER PHARMACY. Acta Polymerica Sinica, 2013, 0(6): 733-749.

鏈接本文:  

     或     

1 Zeuzem S, Feinman S V,Rasenack J,Heathcote E J,Lai M Y,Gane E.New Engl J Med,2000,343(23):1666~1672
2 Ringsdorf H.J Polym Sci PartC-Polym Symposium,1975,(51):135~153
3 Gros L,Ringsdorf H,Schupp H.Angew Chem Int Edit,1981,20(4):305~325
4 Hu X,Jing X.Expert Opin Drug Del,2009,6(10):1079~1090
5 Pasut G,Veronese F M.Adv Drug Del Rev,2009,61(13):1177~1188
6 Reddy K R,Modi M W,Pedder S.Adv Drug Del Rev,2002,54(4):571~586
7 Veronese F M,Mero A.Biodrugs,2008,22(5):315~329
8 Li C,Wallace S.Adv Drug Del Rev,2008,60(8):886~898
9 Greco F,Vicent M J.FrontBiosci-Landmark,2008,13:2744~2756
10 Lammers T,Ulbrich K.Adv Drug Del Rev,2010,62(2):119~121
11 Ulbrich K,Subr V.Adv Drug Del Rev,2010,62(2):150~166
12 Satchi R,Connors TA,Duncan R.Brit J Cancer,2001,85(7):1070~1076
13 Satchi-Fainaro R,Hailu H,Davies J W,Summerford C,Duncan R.Bioconjugate Chem,2003,14(4):797~804
14 McNamara MV,Doroshow JH,Dupont J,Spriggs D,Eastham E,Pezzulli S.J Clin Oncol,2004,22(14):145S~S
15 Li C,Yu D F,Newman R A,Cabral F,Stephens L C,Hunter N,Milas L,Wallace S.Cancer Res,1998,58(11):2404~2409
16 Greenwald R B.J Control Release,2001,74(1-3):159~171
17 Greenwald R B,Conover C D,Choe Y H.Crit Rev Ther Drug,2000,17(2):101~161
18 Greenwald R B,Gilbert C W,Pendri A,Conover C D,Xia J,Martinez A.J Med Chem,1996,39(2):424~431
19 Pendri A,Conover C D,Greenwald R B.Anti-Cancer Drug,1998,13(5):387~395
20 Agnihotri S A,Mallikarjuna N N,Aminabhavi T M.J Control Release 2004,100(1):5~28
21 Kumar M.Reac Funct Polym,2000,46(1):1~27
22 Roy K,Mao H Q,Huang S K,Leong K W.Nat Med,1999,5(4):387~391
23 SugaharaS-i,Kajiki M,Kuriyama H,Kobayashi T R.J Control Release,2007,117(1):40~50
24 Sugahara S,Kajiki M,Kuriyama H,Kobayashi T R.Bio Pharm Bull,2002,25(5):632~641
25 Kim D W,Kim S Y,Kim H K,Kim S W,Shin S W,Kim J S.Ann Oncol,2007,18(12):2009~2014
26 Lee K S,Chung H C,Im S A,Park Y H,Kim C S,KimS-B,Rha S Y,Lee M Y,Ro,J.Breast Cancer Res Tr,2008,108(2):241~250
27 Kim T Y,Kim D W,Chung J Y,Shin S G,Kim S C,Heo D S,Kim N K,Bang Y J.Clin Cancer Re,2004,10(1):3708~3716
28 Hamaguchi T,Kato K,Yasui H,Morizane C,Ikeda M,Ueno H,Muro K,Yamada Y,Okusaka T,Shirao K,Shimada Y,Nakahama H,Matsumura Y.Bri J Cancer,2007,97(2):170~176
29 Hamaguchi T,Matsumura Y,Suzuki M,Shimizu K,Goda R,Nakamura I,Nakatomi I,Yokoyama M,Kataoka K,Kakizoe T.Bri J Cancer,2005,92(7):1240~1246
30 Negishi T,Koizumi F,Uchino H,Kuroda J,Kawaguchi T,Naito S,Matsumura Y.Bri J Cancer,2006,95(5):601~606
31 Zhang X F,Li Y X,Chen X S,Wang X H,Xu X Y,Liang Q Z,Hu J,Jing X.Biomaterials,2005,26(14):2121~2128
32 Xie Z,Guan H,Chen X,Lu C,Chen L,Hu X,Shi Q,Jing X.J Control Release,2007,117(2):210~216
33 Shahin M,Lavasanifar A.Int J Pharmaceut,2010,389(1-2):213~222
34 Gong J,Chen M,Zheng Y,Wang S,Wang Y.J Control Release,2012,159(3):312~323
35 Matsumura Y,Hamaguchi T,Ura T,Muro K,Yamada Y,Shimada Y,Shirao K,Okusak T,Ueno H,Ikeda M,Watanabe N.Bri J Cancer,2004,91(10):1775~1781
36 Yang J,Liu W,Sui M,Tang J,Shen Y.Biomaterials,2011,32(34):9136~9143
37 Wang J,Liu W,Tu Q,Wang J,Song N,Zhang Y,Nie N,Wang J.Biomacromolecules,2011,12(1):228~234
38 Clementi C,Miller K,Mero A,Mol Pharmaceut,2011,8(4):1063~1072
39 Miller K,Eldar-Boock A,Polyak D,Segal E,Benayoun L,Shaked Y,Satchi-Fainaro R.Mol Pharmaceut,2011,8(4):1052~1062
40 Etrych T,Sirova M,Starovoytova L,Rihova B,Ulbrich K.Mol Pharmaceut,2010,7(4):1015~1026
41 Chen W,Shi Y,Feng H,Du M,Zhang J Z,Hu J,Yang D.J Phys Chem B,2012,116(30):9231~9237
42 Grundker C,Volker P,Griesinger F,Ramaswamy A,Nagy A,Schally A V,Emons G.Am J Obstet Gynecol,2002,187(3):528~537
43 Koppan M,Nagy A,Schally A V,Plonowski A,Halmos G,Arencibia J M,Groot K.Prostate,1999,38(2):151~158
44 Nagy A,Schally A V,Armatis P,Szepeshazi K,Halmos G,Kovacs M,Zarandi M,Groot K,Miyazaki M,Jungwirth A,Horvath J.PNAS,1996,93(14):7269~7273
45 Tong R,Cheng J.J Am Chem Soc,2009,131(13):4744~4754
46 Etrych T,Chytil P,Jelinkova M,Rihova B,Ulbrich K.Macromol Biosci,2002,2(1):43~52
47 Hruby M,Konak C,Ulbrich K.J Control Release,2005,103(1):137~148
48 Nakanishi T,Fukushima S,Okamoto K,Suzuki M,Matsumura Y,Yokoyama M,Okano T,Sakurai Y,Kataoka K.J Control Release,2001,74(1-3):295~302
49 Mo G,Hu X,Liu S,Yue J,Wang R,Huang Y,Jing X.Eur J Pharm Sci,2012,46(5):329~335
50 Hu X,Liu S,Huang Y,Chen X,Jing X.Biomacromolecules,2010,11(8):2094~2102
51 Hu X,Wang R,Yue J,Liu S,Xie Z,Jing X.J Mater Chem,2012,22:13303~13310
52 Zhan F,Chen W,Wang Z,Lu W,Cheng R,Deng C,Meng F,Liu H,Zhong Z.Biomacromolecules,2011,12:3612~3620
53 Zhou L,Cheng R,Tao H,Ma S,Guo W,Meng F,Liu H,Liu Z,Zhong Z.Biomacromolecules,2011,12:1460~1467
54 MacKay J A,Chen M,McDaniel J R,Liu W,Simnick A J,Chilkoti A.Nat Mater,2009,8(12):993~999
55 Lee C C,Gillies E R,Fox ME,Guillaudeu S J,Frechet J M J,Dy E E,Szoka F C,PNAS,2006,103(45):16649~16654
56 Cleare M J,Hydes P C,Malerbi B W,Watkins D M.Biochimie,1978,60(9):835~850
57 Reithofer M R,Valiahdi S M,Jakupec M A,Arion V B,Egger A,Galanski M,Keppler B K.J Med Chem,2007,50(26):6692~6699
58 Kolishetti N,Dhar S,Valencia P M,Lin L Q,Karnik R,Lippard S J,Langer R,Farokhzad,O C.PNAS,2010,107(42):17939~17944
59 Xiao H,Qi R,Liu S,Hu X,Duan T,Zheng Y,Huang Y,Jing X.Biomaterials,2011,32(30):7732~7739
60 Dhar S,Daniel W L,Giljohann D A,Mirkin C A,Lippard S J.J Am Chem Soc,2010;132(48):17335
61 Farrer N J,Woods J A,Munk V P,Mackay F S,Sadler P J.Chem Res Toxicol,2010,23(2):413~421
62 Bednarski P J,Mackay F S,Sadler P J.Anti-Cancer Agent Me,2007,7(1):75~93
63 Kasparkova J,Mackay F S,Brabec V,Sadler P J.J Biol Inorg Chem,2003,8(7):741~745
64 Wheate N J,Collins J G.Curr Med Chem,2005,5(3):267~279
65 Wheate N J,Collins J G.Coordin Chem Rev,2003,241(1-2):133~145
66 Nishiyama N,Yokoyama M,Aoyagi T,Okano T,Sakurai Y,Kataoka K.Langmuir,1999,15(2):377~383
67 Nishiyama N,Kato Y,Sugiyama Y,Kataoka K.Pharmaceut Res,2001,18(7):1035~1041
68 Cabral H,Nishlyama N,Kataoka K.J Control Release,2007,121(3):146~155
69 Osada K,Christie R J,Kataoka K.J Roy Soc,2009,6:S325~S39
70 Uchino H,Matsumura Y,Negishi T,Koizumi F,Hayashi T,Honda T,Nishiyama N,Kataoka K,Naito S,Kakizoe T.Bri J Cancer,2005,93(6):678~687
71 Sood P,Thurmond K B,II,Jacob J E,Waller L K,Silva G O,Stewart D R.Bioconjugate Chem,2006,17(5):1270~1279
72 Nowotnik D P,Cvitkovic E.Adv Drug Del Rev,2009,61(13):1214~1219
73 Rademaker-Lakhai J M,Terret C,Howell S B,Baud C M,de Boer R F,Pluim D,Beijnen J H,Schellens J H M,Droz J P.Clin Cancer Res,2004,10(10):3386~3395
74 Lin X,Zhang Q,Rice J R,Stewart D R,Nowotnik D P,Howell S B.Eur J Cancer,2004,40(2):291~297
75 Gianasi E,Buckley R G,Latigo J,Wasil M,Duncan R.J Drug Target,2002,10(7):549~556
76 Xiao H,Zhou D,Liu S,Qi R,Zheng Y,Huang Y,Jing X.Macromol Biosci,2012,12(3):367~373
77 Xiao H,Zhou D,Liu S,Zheng Y,Huang Y,Jing X.Acta Biomater,2012,8(5):1859~1868
78 Rieter W J,Pott K M,Taylor KML,Lin W.J Am Chem Soc,2008,130(35):11584
79 Feazell R P,Nakayama-Ratchford N,Dai H,Lippard S J.J Am Chem Soc,2007,129(27):8438
80 Dhar S,Daniel W L,Giljohann D A,Mirkin C A,Lippard S J.J Am Chem Soc,2009,131(41):14652
81 Dhar S,Kolishetti N,Lippard S J,Farokhzad O C.PNAS,2011,108(5):1850~1855
82 Xiao H,Song H,Yang Q,Cai H,Qi R,Yan L,Liu S,Zheng Y,Huang Y,Liu T,Jing X.Biomaterials,2012,33(27):6507~6519
83 Song H,Wang R,Xiao H,Cai H,Zhang W,Xie Z,Huang Y,Jing X,Liu T.Euro J Pharm Biopharm,2013,83:63~75
84 Brabec V,Kasparkova J,Vrana O,Novakova O,Cox J W,Qu Y,Farrell N.Biochemistry,1999,38(21):6781~6790
85 Kasparkova J,Zehnulova J,Farrell N,Brabec V.J Biol Chem,2002,277(50):48076~48086
86 Wheate N J,Buck D P,Day A I,Collins J G.Dalton T,2006,(3):451~458
87 Xiao H,Song H,Zhang Y,Qi R,Wang R,Xie Z,Huang Y,Li Y,Wu Y,Jing X.Biomaterials,2012,33(33):8657~8669
88 Wang R,Hu X,Xiao H,Xie Z,Huang Y,Jing X.J Mater Chem B,2013,1:744~748
89 Chen F,Dong D,Fu Y,Zheng Y,Liu S,Chang M,Jing X.Chem Res Chinese Universities,2012,28(4):656~661
90 Yoo H S,Park T G.J Control Release,2004,100(2):247~256
91 Bae Y,Jang WD,Nishiyama N,Fukushima S,Kataoka K.Mol Biosyst,2005,1(3):242~250
92 Julyan P J,Seymour L W,Ferry D R,Daryani S,Boivin C M,Doran J,David M,Anderson D,Christodoulou C,Young A M,Hesslewood S,Kerr D J.J Control Release,1999,57(3):281~290
93 Ferry D R,Seymour L W,Anderson D,Hesselwood S,Julyan P,Boivin C,Poyner R,Guest P,Doran J,Kerr D J.Cancer,1999,80:21
94 Hu Z,Luo F,Pan Y,Hou C,Ren L,Chen J,Wang J,Zhang Y.J Biomed Mater Res A,2008,85A(3):797~807
95 Xiao H,Li W,Qi R,Yan L,Wang R,Liu S,Zheng Y,Xie Z,Huang Y,Jing X.J Control Release,2012,163:304~314
96 Song H,Xiao H,Zhang Y,Cai H,Wang R,Zheng Y,Huang Y,Li Y,Xie Z,Liu T,Jing X.J Mater Chem B,2013,1:762~772
97 Xiao H,Yan L,Zhang Y,Qi R,Li W,Wang R,Liu S,Huang Y,Li Y,Jing X.Chem Commun,2012,48:10730~10732
98 Wang R,Xiao H,Song H,Zhang Y,Hu X,Xie Z,Huang Y,Jing X,Li Y.J Mater Chem,2012,22:25453~25462

[1] 周念恩;陳衢生;卓仁禧. 高分子藥物研究——ⅩⅦ. 二羥烷基嘧啶與N,N’-雙(2-氯乙基) 二氯磷酰胺縮聚物的合成及其抗腫瘤活性研究[J]. Acta Polymerica Sinica, 1987, 1(6): 417-422.

[2] 陳衢生;卓仁禧;周念恩. 高分子藥物研究——ⅪⅤ.含核酸堿基和氮芥的聚磷酸酯的合成及其抗腫瘤活性初步研究[J]. Acta Polymerica Sinica, 1987, 1(3): 216-221.

  本文關(guān)鍵詞：高分子藥物學(xué)的研究進(jìn)展與期盼，由筆耕文化傳播整理發(fā)布。