Injectable sustained release microparticles of curcumin: a new concept for cancer chemoprevention.
Poor oral bioavailability limits the use of curcumin and other dietary polyphenols in the prevention and treatment of cancer. Minimally invasive strategies that can provide effective and sustained tissue concentrations of these agents will be highly valuable tools in the fight against cancer. The objective of this study was to investigate the use of an injectable sustained release microparticle formulation of curcumin as a novel approach to breast cancer chemoprevention. A biodegradable and biocompatible polymer, poly(d,l-lactide-co-glycolide), was used to fabricate curcumin microparticles. When injected s.c. in mice, a single dose of microparticles sustained curcumin levels in the blood and other tissues for nearly a month. Curcumin levels in the lungs and brain, frequent sites of breast cancer metastases, were 10- to 30-fold higher than that in the blood. Further, curcumin microparticles showed marked anticancer efficacy in nude mice bearing MDA-MB-231 xenografts compared with other controls. Repeated systemic injections of curcumin were not effective in inhibiting tumor growth. Treatment with curcumin microparticles resulted in diminished vascular endothelial growth factor expression and poorly developed tumor microvessels, indicating a significant effect on tumor angiogenesis. These results suggest that sustained delivery of chemopreventives such as curcumin using polymeric microparticles is a promising new approach to cancer chemoprevention and therapy.
Shahani
Komal
K
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
Swaminathan
Suresh Kumar
SK
Freeman
Diana
D
Blum
Angela
A
Ma
Linan
L
Panyam
Jayanth
J
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019938:Cyclin D1 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D003692:Delayed-Action Preparations; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011897:Random Allocation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D051546:Cyclooxygenase 2; D020780:Matrix Metalloproteinase 9; D003474:Curcumin
Drug Metab Dispos. 1999 Apr;27(4):486-94
10101144
Biochem Biophys Res Commun. 1998 Apr 17;245(2):493-6
9571182
Mol Cancer. 2008 Jan 29;7:16
18226269
J Biomed Mater Res. 2002 Aug;61(2):180-7
12007197
J Altern Complement Med. 2003 Feb;9(1):161-8
12676044
Biochem Pharmacol. 2008 Feb 15;75(4):787-809
17900536
Chem Pharm Bull (Tokyo). 1996 Oct;44(10):1935-40
8904823
Int J Mol Med. 2000 Nov;6(5):521-6
11029517
Clin Cancer Res. 2005 Oct 15;11(20):7490-8
16243823
Pharm Res. 1987 Dec;4(6):465-71
3508558
Clin Cancer Res. 2008 Apr 1;14(7):2128-36
18381954
Acta Pharmacol Sin. 2007 Sep;28(9):1262-73
17723162
Int J Cancer. 2009 Nov 1;125(9):2187-97
19623659
Br J Cancer. 2002 May 20;86(10):1566-77
12085206
Free Radic Biol Med. 2008 Nov 15;45(10):1403-12
18762247
J Pathol. 2001 Jun;194(2):254-61
11400156
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Jun 15;853(1-2):183-9
17400527
Oncogene. 1999 Oct 28;18(44):6013-20
10557090
Biochem Pharmacol. 2005 Apr 15;69(8):1205-13
15794941
Cell Physiol Biochem. 2007;19(1-4):137-52
17310108
Genes Dev. 1993 May;7(5):812-21
8491378
Int J Pharm. 2008 Dec 8;364(2):298-327
18621492
Carcinogenesis. 2004 Sep;25(9):1671-9
15073046
Cancer. 2005 Sep 15;104(6):1322-31
16092118
Int J Pharm. 2007 Jun 29;338(1-2):180-90
17336474
Mol Pharm. 2007 Nov-Dec;4(6):807-18
17999464
Cancer. 2003 Mar 1;97(5):1321-31
12599241
Nat Rev Cancer. 2005 Aug;5(8):591-602
16056258
J Control Release. 2008 Apr 21;127(2):137-45
18282629
Int J Pharm. 2001 Jun 4;220(1-2):91-9
11376971
Cancer Res. 2006 Jan 15;66(2):613-21
16423986
J Clin Oncol. 1987 Jun;5(6):912-7
2953870
Biochem Pharmacol. 2005 Sep 1;70(5):700-13
16023083
Br J Cancer. 2004 Mar 8;90(5):1011-5
14997198
Mol Pharmacol. 2006 Jan;69(1):195-206
16219905
Int J Pharm. 2005 Sep 14;301(1-2):217-25
16040213
Mol Nutr Food Res. 2008 Jun;52 Suppl 1:S103-27
18496811
Oncogene. 2002 Dec 12;21(57):8852-61
12483537
AAPS J. 2006 Jul 07;8(3):E443-9
17025261
J Surg Oncol. 1983 Jul;23(3):175-80
6345937
Mol Cell Biochem. 2009 May;325(1-2):107-19
19191010
Cancer Lett. 1996 Jun 5;103(2):137-41
8635149
Cancer Res. 2003 Aug 1;63(15):4342-6
12907602
Neurosci Lett. 2008 Dec 5;447(1):48-53
18838107
Anticancer Res. 2001 Jul-Aug;21(4B):2895-900
11712783
Nat Rev Cancer. 2004 Jun;4(6):423-36
15170445
Oncogene. 1999 Dec 20;18(55):7908-16
10630643
Adv Drug Deliv Rev. 1997 Oct 13;28(1):5-24
10837562
Int Urol Nephrol. 2001;33(2):379-83
12092661
Clin Cancer Res. 2004 Oct 15;10(20):6847-54
15501961
Acta Pharmacol Sin. 2007 Sep;28(9):1274-304
17723163