Systemic Administration of Polymeric Nanoparticle-Encapsulated Curcumin (NanoCurc) Blocks Tumor Growth and Metastases in Preclinical Models of Pancreatic Cancer

Abstract

Curcumin or diferuloylmethane is a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa). A large volume (several hundreds) of published reports has established the anticancer and chemopreventative properties of curcumin in preclinical models of every known major cancer type. Nevertheless, the clinical translation of curcumin has been significantly hampered due to its poor systemic bioavailability, which mandates that patients consume up to 8 to 10 g of the free drug orally each day to achieve detectable levels in circulation. We have engineered a polymeric nanoparticle encapsulated curcumin formulation (NanoCurc) that shows remarkably higher systemic bioavailability in plasma and tissues compared with free curcumin upon parenteral administration. In xenograft models of human pancreatic cancer established in athymic mice, administration of parenteral NanoCurc significantly inhibits primary tumor growth in both subcutaneous and orthotopic settings. The combination of parenteral NanoCurc with gemcitabine results in enhanced tumor growth inhibition versus either single agent, suggesting an additive therapeutic influence in vivo. Furthermore, this combination completely abrogates systemic metastases in orthotopic pancreatic cancer xenograft models. Tumor growth inhibition is accompanied by significant reduction in activation of nuclear factor-κB, as well as significant reduction in expression of matrix metalloproteinase-9 and cyclin D1, in xenografts treated with NanoCurc and gemcitabine. NanoCurc is a promising new formulation that is able to overcome a major impediment for the clinical translation of curcumin to cancer patients by improving systemic bioavailability, and by extension, therapeutic efficacy. Mol Cancer Ther; 9(8); 2255-64. ©2010 AACR.

Interaction of curcumin nanoformulations with human plasma proteins and erythrocytes

“…In vivo studies of PLGA and polyNI-PAM nanogel curcumin formulations have shown improved bioavailability, and therefore are more effective systems for delivering curcumin into tumors. 12,14,16,72,73 These data clearly support the overall conclusion of this study. Our future research efforts will include evaluation of the in vivo pharmacokinetics of these curcumin nanoformulations to clarify the underlying mechanisms for potential cancer therapeutics.…”

Polyphenols delivery by polymeric materials: challenges in cancer treatment

“…The association with CP is also useful for ovarian cancer treatment (Yallapu et al, 2010b), while in vivo studies proved the synergism of CUR nanoformulation prepared by free radical polymerization of NIPAAm, VP, and AA with Gemcitabine in Pa03C Xenograft mouse model (Bisht et al, 2010).…”

Melanoma therapy with transdermal mitoxantrone cubic phases

“…The CRT expression on the cell surfaces of the B 16 cells was evaluated using the anti-CRT antibody (Bisht et al, 2010). Tumor sections on the silane-coated slides were deparaffinized with xylene and dehydrated with ethanol.…”