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. Cancer Res; 70(11); 4443-52. ©2010 AACR.

Curcumin suppresses HIF1A synthesis and VEGFA release in pituitary adenomas

“…Although the efficacy of curcumin is currently under investigation in several clinical trials, its usage is limited by its poor bioavailability, which is due to very rapid renal excretion and hepatic degradation (Shehzad et al 2010). More stable curcumin derivatives or curcumin-releasing microparticles, which have successfully been applied in recent studies (Thomas et al 2008, Shahani et al 2010, may overcome this problem in the future.…”

Experimental Therapeutics for the Treatment of Triple Negative Breast Cancer

“…Additionally, the relative expression of MMP-9 in tumors from the curcumin PLGA-microparticle treated group was decreased 57% compared to control, while Ki-67 and cyclin D1 were decreased by 45% and 52%, respectively. There was also a 2.5-fold increase in the number of apoptotic cells compared to blank PLGA-microparticle treatment (Shahani et al, 2010). Since repeated systemic dosing of curcumin had no effect on tumor cell proliferation, apoptosis, or the relative cyclin D1 expression, the study concluded that sustained release microparticles of curcumin are more effective than repeated systemic injections of curcumin for breast cancer chemoprevention.…”

“…Specifically, the curcumin PLGA-microparticles treated group showed smaller and less well developed CD31 positive microvessels compared to curcumin alone. Furthermore, treatment with curcumin PLGA-microparticles decreased the relative VEGF expression in tumors by 78%, compared with control (Shahani et al, 2010). Additionally, the relative expression of MMP-9 in tumors from the curcumin PLGA-microparticle treated group was decreased 57% compared to control, while Ki-67 and cyclin D1 were decreased by 45% and 52%, respectively.…”

“…Specifically, a single dose of subcutaneously injected PLGA-microparticles sustained curcumin levels in the blood for a month whereas single or multiple i.p. injections of curcumin resulted in a shorter half-life (Shahani et al, 2010). In addition, the curcumin concentration was 10-30-fold higher in the lungs and brain than in the blood.…”

“…In addition, the curcumin concentration was 10-30-fold higher in the lungs and brain than in the blood. Furthermore, curcumin inhibited the growth of tumors in an MDA-MB-231 mouse xenograft model by 49% compared to the mice treated with blank PLGA-microparticles (Shahani et al, 2010). Mechanisms for this effect were attributed to the down regulation of the markers of angiogenesis, metastasis and proliferation.…”