title: Novel mixed polymeric micelles for enhancing delivery of anticancer drug and overcoming multidrug resistance in tumor cell lines simultaneously.
abstract: OBJECTIVE
  To evaluate novel mixed polymeric micelles based on monomethoxy poly(ethylene glycol)-poly(D,L-lactic acid) (mPEG-PLA) and Pluronic L61 for delivery of paclitaxel (PTX) to circumvent unfavorable effects resulting from Cremophore EL in Cremophore EL-based PTX formulation and overcoming multidrug resistance (MDR) in tumor cells at the same time.
  
  
  METHODS
  PTX-loaded plain micelles and mixed micelles were prepared and characterized by determining PTX release in vitro, MDR reversal effect in human breast cancer MDR MCF-7/ADR cell sublines and pharmacokinetics in vivo.
  
  
  RESULTS
  Both PTX-loaded plain micelles and mixed micelles had similar in vitro release profile. Mixed micellar PTX significantly reduced IC(50) of PTX in MCF-7/ADR cells compared to free PTX and plain micellar PTX, and mixed micelles substantially enhanced cellular accumulation of R 123 in MCF-7/ADR cells compared to free R123 and plain micelles. PTX-loaded mixed micelles with lower content of L61 exhibited comparable cytotoxicity to that observed with Cremophore EL-based PTX formulation in inhibiting the growth of MCF-7/ADR cells. Moreover, plain micelles and mixed micelles retained the pharmacokinetic characteristics of PTX in rats compared with Cremophore EL-based PTX formulation.
  
  
  CONCLUSIONS
  This study suggested that the mixed micelles could enhance delivery of PTX and cell-killing effect for MDR MCF-7/ADR cells.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences Peking University, Beijing, 100191, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Li
authors.forename: Pingzhu
authors.initials: P
authors.lastname: Li
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xingwei
authors.initials: X
authors.lastname: Chen
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D004339:Drug Compounding; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage*; D010316:Particle Size; D020442:Poloxamer / Q000493:pharmacokinetics*; D011091:Polyesters / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); C480965:pluronic L61; D020442:Poloxamer; D011092:Polyethylene Glycols; D017239:Paclitaxel
references.citation: Eur J Cancer. 1996 Jun;32A(6):1070-81
references.pmid: 8763349
references.citation: Pharm Res. 1998 Jun;15(6):850-5
references.pmid: 9647349
references.citation: Int J Pharm. 2002 Mar 20;235(1-2):179-92
references.pmid: 11879753
references.citation: J Biol Chem. 1992 Dec 15;267(35):24995-5002
references.pmid: 1360981
references.citation: Int J Cancer. 1996 Jan 26;65(3):389-97
references.pmid: 8575863
references.citation: Eur J Cancer. 2001 Sep;37(13):1590-8
references.pmid: 11527683
references.citation: Int J Pharm. 2007 Jun 7;337(1-2):63-73
references.pmid: 17289311
references.citation: J Clin Oncol. 1990 Jul;8(7):1263-8
references.pmid: 1972736
references.citation: Adv Drug Deliv Rev. 2001 Mar 23;47(1):113-31
references.pmid: 11251249
references.citation: J Control Release. 2003 May 20;89(3):437-46
references.pmid: 12737846
references.citation: Curr Pharm Des. 2006;12(36):4669-84
references.pmid: 17168771
references.citation: Oncogene. 2003 Oct 20;22(47):7512-23
references.pmid: 14576855
references.citation: J Biomed Mater Res A. 2008 May;85(2):539-46
references.pmid: 17729259
references.citation: Crit Rev Ther Drug Carrier Syst. 2002;19(1):1-72
references.pmid: 12046891
references.citation: Adv Drug Deliv Rev. 2002 Feb 21;54(2):191-202
references.pmid: 11897145
references.citation: Br J Cancer. 2001 Dec 14;85(12):1987-97
references.pmid: 11747344
references.citation: J Clin Oncol. 1998 Sep;16(9):2964-76
references.pmid: 9738565
references.citation: Eur J Pharm Biopharm. 1999 Sep;48(2):101-11
references.pmid: 10469928
references.citation: Cell Mol Life Sci. 2003 Jan;60(1):21-37
references.pmid: 12613656
references.citation: Trends Biochem Sci. 2006 Mar;31(3):164-72
references.pmid: 16483782
references.citation: Eur J Pharm Sci. 2000 Oct;11(4):265-83
references.pmid: 11033070
references.citation: Adv Drug Deliv Rev. 2002 Sep 13;54(5):759-79
references.pmid: 12204601
references.citation: Jpn J Cancer Res. 2002 Nov;93(11):1237-43
references.pmid: 12460465
references.citation: Proc Natl Acad Sci U S A. 1987 Jan;84(1):265-9
references.pmid: 2432605
references.citation: Pharm Res. 1999 Sep;16(9):1373-9
references.pmid: 10496652
references.citation: Curr Opin Genet Dev. 1996 Oct;6(5):610-7
references.pmid: 8939727
references.citation: Nat Rev Drug Discov. 2006 Mar;5(3):219-34
references.pmid: 16518375
references.citation: Curr Drug Targets. 2004 May;5(4):333-46
references.pmid: 15134216
references.citation: J Control Release. 2004 Jun 18;97(2):249-57
references.pmid: 15196752
references.citation: Pharm Res. 2008 Mar;25(3):500-11
references.pmid: 17896100
references.citation: Cancer Chemother Pharmacol. 1997;39(6):557-60
references.pmid: 9118471
references.citation: Cancer Commun. 1990;2(9):297-303
references.pmid: 1976341
references.citation: Bioconjug Chem. 1997 Sep-Oct;8(5):649-57
references.pmid: 9327127
references.citation: Bioconjug Chem. 1996 Mar-Apr;7(2):209-16
references.pmid: 8983343
references.citation: Pharm Res. 2004 Feb;21(2):201-30
references.pmid: 15032302
references.citation: J Pharmacol Exp Ther. 2001 Feb;296(2):551-7
references.pmid: 11160643
references.citation: Crit Rev Ther Drug Carrier Syst. 2003;20(5):357-403
references.pmid: 14959789
references.citation: J Control Release. 2001 May 14;72(1-3):191-202
references.pmid: 11389998
references.citation: Curr Drug Targets. 2006 Jul;7(7):813-21
references.pmid: 16842213
references.citation: Clin Chem Lab Med. 2002 Sep;40(9):918-25
references.pmid: 12435109
references.citation: J Biomed Mater Res A. 2008 Jul;86(1):48-60
references.pmid: 17941015
references.citation: Cancer Res. 1996 Aug 15;56(16):3626-9
references.pmid: 8705995
references.citation: Nat Rev Cancer. 2002 Jan;2(1):48-58
references.pmid: 11902585
references.citation: Cancer Control. 2003 Mar-Apr;10(2):159-65
references.pmid: 12712010
references.citation: Clin Cancer Res. 2000 Aug;6(8):3205-14
references.pmid: 10955805
references.citation: Br J Cancer. 1996 Nov;74(10):1545-52
references.pmid: 8932333
references.citation: J Control Release. 2005 Jan 3;101(1-3):59-68
references.pmid: 15588894
references.citation: Biochim Biophys Acta. 2004 Mar 1;1644(2-3):229-49
references.pmid: 14996506
references.citation: J Drug Target. 2009 Dec;17(10):739-50
references.pmid: 19863195
references.citation: J Natl Cancer Inst. 1993 Oct 20;85(20):1685-90
references.pmid: 8105099
references.citation: Lung Cancer. 2005 Sep;49(3):337-43
references.pmid: 15955594
references.citation: Br J Cancer. 2004 Nov 15;91(10):1775-81
references.pmid: 15477860
references.citation: Oncologist. 1996;1(3):151-158
references.pmid: 10387981
references.citation: J Control Release. 2007 Dec 20;124(3):134-43
references.pmid: 17928087
references.citation: Cancer Chemother Pharmacol. 1997;40(1):81-6
references.pmid: 9137535
references.citation: Biochim Biophys Acta. 1988 Feb 18;938(2):315-21
references.pmid: 2893642
references.citation: J Control Release. 2004 Sep 14;99(1):83-101
references.pmid: 15342183
references.citation: World J Surg. 2000 Oct;24(10):1183-6
references.pmid: 11071457
references.citation: Arch Biochem Biophys. 1995 May 10;319(1):309-15
references.pmid: 7771801
references.citation: Br J Cancer. 2004 Jun 1;90(11):2085-91
references.pmid: 15150584
references.citation: Pharm Res. 1998 Oct;15(10):1525-32
references.pmid: 9794493
references.citation: Br J Cancer. 2000 Aug;83(3):366-74
references.pmid: 10917553
references.citation: Pharm Res. 2003 Oct;20(10):1581-90
references.pmid: 14620511
references.citation: Eur J Pharm Biopharm. 2007 Jun;66(3):303-17
references.pmid: 17481869
references.citation: J Control Release. 2008 Nov 12;131(3):220-7
references.pmid: 18722489