title: Disposition of drugs in block copolymer micelle delivery systems: from discovery to recovery.
abstract: Since their discovery in the early 1980s, polymeric micelles have been the subject of several studies as delivery systems that can potentially improve the therapeutic performance and modify the toxicity profile of encapsulated drugs by changing their pharmacokinetic characteristics. The efforts in this area have led in recent years to the advancement of several polymeric micellar formulations to clinical trials, some of which have shown promise in changing the biodistribution of the incorporated drug after intravenous administration as a means of tumour-targeted drug delivery. Recently, the possible benefit of polymeric micellar delivery in enhancing the absorption and bioavailability of incorporated drugs from alternative routes of drug administration has attracted interest. This article provides an overview of the effect of polymeric micellar delivery on absorption, distribution, metabolism and excretion of incorporated therapeutic agents. It also aims to assess the current information on the performance of polymeric micellar delivery systems in modifying the pharmacokinetics/pharmacodynamics of the incorporated drugs in clinical trials, and to re-examine the important structural factors required for successful design of polymeric micellar delivery systems capable of inducing favourable changes in the pharmacokinetics of the encapsulated drug.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Hamidreza Montazeri
authors.initials: HM
authors.lastname: Aliabadi
authors.forename: Mostafa
authors.initials: M
authors.lastname: Shahin
authors.forename: Dion R
authors.initials: DR
authors.lastname: Brocks
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Lavasanifar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D016503:Drug Delivery Systems; D006801:Humans; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D010599:Pharmacokinetics; D011108:Polymers; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D004364:Pharmaceutical Preparations; D011108:Polymers
references.citation: Biomaterials. 2006 Dec;27(34):5855-60
references.pmid: 16919723
references.citation: Biopharm Drug Dispos. 1997 Oct;18(7):623-33
references.pmid: 9330782
references.citation: Pharm Res. 2001 Jul;18(7):1035-41
references.pmid: 11496942
references.citation: J Control Release. 2000 Feb 14;64(1-3):143-53
references.pmid: 10640653
references.citation: Int J Pharm. 2007 Oct 1;343(1-2):34-40
references.pmid: 17537601
references.citation: Clin Pharmacokinet. 2003;42(5):419-36
references.pmid: 12739982
references.citation: Arch Pharm Res. 2007 Sep;30(9):1138-43
references.pmid: 17958332
references.citation: J Control Release. 2001 Nov 9;77(1-2):155-60
references.pmid: 11689268
references.citation: J Control Release. 2005 Jan 3;101(1-3):223-32
references.pmid: 15588907
references.citation: Pharm Res. 2005 Feb;22(2):209-19
references.pmid: 15783068
references.citation: J Control Release. 2007 Mar 12;118(1):105-17
references.pmid: 17258837
references.citation: Eur J Pharm Biopharm. 1999 Sep;48(2):101-11
references.pmid: 10469928
references.citation: Clin Cancer Res. 2004 Jun 1;10(11):3708-16
references.pmid: 15173077
references.citation: Br J Cancer. 2005 Sep 19;93(6):678-87
references.pmid: 16222314
references.citation: Vet Immunol Immunopathol. 2007 Oct 15;119(3-4):299-302
references.pmid: 17628697
references.citation: Am J Health Syst Pharm. 2004 Dec 1;61(23):2541-4
references.pmid: 15595229
references.citation: Jpn J Cancer Res. 2001 Mar;92(3):328-36
references.pmid: 11267944
references.citation: Pharm Res. 1999 Sep;16(9):1373-9
references.pmid: 10496652
references.citation: Br J Cancer. 2007 Jul 16;97(2):170-6
references.pmid: 17595665
references.citation: Int J Pharm. 2001 Oct 23;229(1-2):29-36
references.pmid: 11604255
references.citation: Biomacromolecules. 2005 Sep-Oct;6(5):2462-7
references.pmid: 16153081
references.citation: Pharmacol Res. 2003 Jun;47(6):555-62
references.pmid: 12742011
references.citation: Biomacromolecules. 2007 Jan;8(1):202-8
references.pmid: 17206808
references.citation: Int J Pharm. 2007 Apr 4;334(1-2):156-65
references.pmid: 17118588
references.citation: Drug Dev Ind Pharm. 2005 May;31(4-5):447-54
references.pmid: 16093210
references.citation: J Pharm Sci. 2003 Jul;92(7):1343-55
references.pmid: 12820139
references.citation: Prostate. 2000 Jul 1;44(2):156-63
references.pmid: 10881025
references.citation: Pharm Dev Technol. 2000;5(4):521-32
references.pmid: 11109251
references.citation: J Control Release. 1998 Jan 23;51(1):13-22
references.pmid: 9685900
references.citation: Cell Mol Life Sci. 2004 Oct;61(19-20):2549-59
references.pmid: 15526161
references.citation: J Drug Target. 2005 Aug;13(7):391-7
references.pmid: 16308207
references.citation: Arch Pharm Res. 2006 Oct;29(10):928-33
references.pmid: 17121190
references.citation: Trends Pharmacol Sci. 1994 Jul;15(7):215-20
references.pmid: 7940982
references.citation: Bioconjug Chem. 1996 Mar-Apr;7(2):209-16
references.pmid: 8983343
references.citation: Biomaterials. 2005 Dec;26(35):7251-9
references.pmid: 16005061
references.citation: Adv Drug Deliv Rev. 2002 Feb 21;54(2):235-52
references.pmid: 11897148
references.citation: J Control Release. 2006 Nov 28;116(2):e53-5
references.pmid: 17718968
references.citation: J Control Release. 1998 Feb 12;51(2-3):169-78
references.pmid: 9685914
references.citation: Life Sci. 1999;64(19):1733-8
references.pmid: 10353627
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: Clin Pharmacokinet. 2001;40(7):539-51
references.pmid: 11510630
references.citation: J Am Chem Soc. 2004 Sep 1;126(34):10640-4
references.pmid: 15327322
references.citation: Biochim Biophys Acta. 1991 Jul 1;1066(1):29-36
references.pmid: 2065067
references.citation: Int J Pharm. 2007 Mar 6;332(1-2):161-7
references.pmid: 17055200
references.citation: Pharm Res. 1998 Jun;15(6):850-5
references.pmid: 9647349
references.citation: Eur J Pharm Biopharm. 2007 Mar;65(3):309-19
references.pmid: 17257817
references.citation: J Control Release. 2004 Apr 28;96(2):273-83
references.pmid: 15081218
references.citation: J Control Release. 2004 Dec 10;100(3):389-97
references.pmid: 15567504
references.citation: Ultrasonics. 2004 Apr;42(1-9):943-50
references.pmid: 15047411
references.citation: J Control Release. 2001 Jul 6;74(1-3):295-302
references.pmid: 11489509
references.citation: J Pharmacol Exp Ther. 2003 Feb;304(2):845-54
references.pmid: 12538842
references.citation: Cancer Res. 1990 Mar 15;50(6):1693-700
references.pmid: 2306723
references.citation: Pharm Res. 1993 Jul;10(7):970-4
references.pmid: 8378259
references.citation: Cancer Res. 1996 Aug 15;56(16):3626-9
references.pmid: 8705995
references.citation: Expert Opin Drug Deliv. 2006 Jan;3(1):139-62
references.pmid: 16370946
references.citation: Biochim Biophys Acta. 1989 May 19;981(1):27-35
references.pmid: 2719971
references.citation: Curr Drug Deliv. 2005 Jan;2(1):35-44
references.pmid: 16305406
references.citation: Cancer Res. 2006 Oct 15;66(20):10048-56
references.pmid: 17047068
references.citation: Drug Dev Ind Pharm. 2007 Oct;33(10):1142-50
references.pmid: 17852364
references.citation: J Control Release. 2005 May 18;104(2):289-300
references.pmid: 15907580
references.citation: Arch Pharm Res. 1998 Aug;21(4):418-22
references.pmid: 9875469
references.citation: Pharm Res. 2003 Jan;20(1):24-30
references.pmid: 12608532
references.citation: Prog Lipid Res. 2003 Nov;42(6):463-78
references.pmid: 14559067
references.citation: Int J Pharm. 2006 Nov 15;325(1-2):155-62
references.pmid: 16884870
references.citation: Br J Cancer. 1996 Nov;74(10):1545-52
references.pmid: 8932333
references.citation: Anticancer Drugs. 1997 Aug;8(7):696-701
references.pmid: 9311446
references.citation: J Drug Target. 2007 Nov;15(9):553-84
references.pmid: 17968711
references.citation: AAPS PharmSci. 2002;4(4):E40
references.pmid: 12646011
references.citation: Eur J Pharm Biopharm. 2002 Nov;54(3):299-309
references.pmid: 12445560
references.citation: Pharm Res. 2003 Jul;20(7):1085-92
references.pmid: 12880295
references.citation: Hum Gene Ther. 2004 May;15(5):481-93
references.pmid: 15144578
references.citation: Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11460-4
references.pmid: 1763060
references.citation: J Control Release. 2004 Aug 27;98(3):415-26
references.pmid: 15312997
references.citation: Pharm Res. 2006 Jun;23(6):1243-50
references.pmid: 16715372
references.citation: AAPS PharmSciTech. 2007 Jan 05;8(1):1
references.pmid: 17408209
references.citation: Life Sci. 2000 Sep 8;67(16):2011-6
references.pmid: 11072877
references.citation: Adv Drug Deliv Rev. 2002 Jan 17;54(1):37-51
references.pmid: 11755705
references.citation: Science. 2004 Mar 19;303(5665):1818-22
references.pmid: 15031496
references.citation: J Control Release. 2005 Mar 21;103(2):405-18
references.pmid: 15763623
references.citation: J Control Release. 2005 Feb 16;102(3):657-68
references.pmid: 15681087
references.citation: J Pharm Pharmacol. 2006 Jul;58(7):903-8
references.pmid: 16805949
references.citation: Pharm Res. 2002 Apr;19(4):418-22
references.pmid: 12033373
references.citation: Bioconjug Chem. 1995 Nov-Dec;6(6):639-43
references.pmid: 8608176
references.citation: Int J Pharm. 2000 Nov 19;209(1-2):1-14
references.pmid: 11084241
references.citation: Int J Pharm. 2007 Mar 21;333(1-2):87-94
references.pmid: 17081709
references.citation: J Drug Target. 1999;7(3):171-86
references.pmid: 10680973
references.citation: Prog Lipid Res. 2004 Nov;43(6):489-533
references.pmid: 15522762
references.citation: J Control Release. 2003 Apr 14;89(1):127-40
references.pmid: 12695068
references.citation: Drugs. 1997;54 Suppl 4:8-14
references.pmid: 9361956
references.citation: Drug Dev Ind Pharm. 2002 Jan;28(1):101-5
references.pmid: 11858520
references.citation: Bioconjug Chem. 2004 May-Jun;15(3):441-8
references.pmid: 15149170
references.citation: Br J Cancer. 2004 Nov 15;91(10):1775-81
references.pmid: 15477860
references.citation: J Control Release. 2006 Mar 10;111(1-2):47-55
references.pmid: 16460829
references.citation: J Control Release. 2004 Feb 10;94(2-3):323-35
references.pmid: 14744484
references.citation: Breast Cancer Res Treat. 2008 Mar;108(2):241-50
references.pmid: 17476588
references.citation: Int J Pharm. 2007 Feb 1;329(1-2):158-65
references.pmid: 17008034
references.citation: Biochim Biophys Acta. 1991 Jul 22;1066(2):159-65
references.pmid: 1854781
references.citation: Int J Pharm. 2000 Jan 5;193(2):213-8
references.pmid: 10606784
references.citation: Gene Ther. 2001 Jul;8(13):999-1004
references.pmid: 11438834
references.citation: Pharm Res. 1999 Mar;16(3):396-401
references.pmid: 10213370
references.citation: Int J Pharm. 2000 Jul 20;202(1-2):161-4
references.pmid: 10915939
references.citation: Int J Pharm. 2005 Jul 14;298(1):176-85
references.pmid: 15950411
references.citation: Acta Pharmacol Sin. 2006 Jun;27(6):747-53
references.pmid: 16723095
references.citation: Eur J Pharm Biopharm. 2007 Apr;66(1):11-20
references.pmid: 17085025
references.citation: Cancer Res. 2003 Dec 15;63(24):8977-83
references.pmid: 14695216
references.citation: J Gene Med. 2007 Nov;9(11):956-66
references.pmid: 17724775
references.citation: Pharm Res. 2004 Jul;21(7):1184-91
references.pmid: 15290858
references.citation: J Control Release. 2004 Sep 14;99(1):83-101
references.pmid: 15342183
references.citation: Cancer Chemother Pharmacol. 1997;40(1):81-6
references.pmid: 9137535
references.citation: Pharmazie. 1998 Jul;53(7):466-9
references.pmid: 9742041
references.citation: Crit Rev Ther Drug Carrier Syst. 1992;9(3-4):213-48
references.pmid: 1458544
references.citation: Adv Drug Deliv Rev. 2002 Feb 21;54(2):203-22
references.pmid: 11897146
references.citation: Crit Rev Ther Drug Carrier Syst. 1998;15(5):481-512
references.pmid: 9822868
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: Bioconjug Chem. 1996 Jan-Feb;7(1):144-9
references.pmid: 8742003
references.citation: J Control Release. 2007 Jan 22;117(1):59-67
references.pmid: 17097755
references.citation: Int J Pharm. 2005 Apr 27;294(1-2):247-59
references.pmid: 15814248
references.citation: J Control Release. 2007 Sep 11;122(1):63-70
references.pmid: 17644207
references.citation: Biomaterials. 2001 Jul;22(14):2049-56
references.pmid: 11426885
references.citation: Br J Cancer. 2005 Apr 11;92(7):1240-6
references.pmid: 15785749
references.citation: Ann Oncol. 2007 Dec;18(12):2009-14
references.pmid: 17785767
references.citation: J Control Release. 2005 Jun 20;105(1-2):32-42
references.pmid: 15925422
references.citation: Adv Drug Deliv Rev. 2002 Feb 21;54(2):169-90
references.pmid: 11897144
references.citation: Pharm Res. 1996 Dec;13(12):1838-45
references.pmid: 8987081
references.citation: Br J Cancer. 2006 Sep 4;95(5):601-6
references.pmid: 16909136
references.citation: Cancer Res. 1991 Jun 15;51(12):3229-36
references.pmid: 2039998
references.citation: Eur J Pharm Biopharm. 2007 Jun;66(3):303-17
references.pmid: 17481869
references.citation: J Control Release. 2001 Jun 15;73(2-3):137-72
references.pmid: 11516494
references.citation: Int Immunopharmacol. 2007 Sep;7(9):1259-64
references.pmid: 17630205
references.citation: J Drug Target. 2004;12(8):517-26
references.pmid: 15621677
references.citation: Adv Drug Deliv Rev. 2001 Mar 23;47(1):113-31
references.pmid: 11251249