title: Injectable sustained release microparticles of curcumin: a new concept for cancer chemoprevention.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
authors.forename: Komal
authors.initials: K
authors.lastname: Shahani
authors.forename: Suresh Kumar
authors.initials: SK
authors.lastname: Swaminathan
authors.forename: Diana
authors.initials: D
authors.lastname: Freeman
authors.forename: Angela
authors.initials: A
authors.lastname: Blum
authors.forename: Linan
authors.initials: L
authors.lastname: Ma
authors.forename: Jayanth
authors.initials: J
authors.lastname: Panyam
mesh_terms: 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
chemical_list: 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
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