Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo

Abstract

Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 ± 0.011) with a mean particle size of 27.3 ± 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 ± 1.02%, and drug loading of 12.95 ± 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t(1/2) and AUC of curcumin in vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesis in vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cells in vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg(-1) curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

Self-assembly Polyrotaxanes Nanoparticles as Carriers for Anticancer Drug Methotrexate Delivery

“…The release of MTX/PN-H nanoparticles was a little slower than that of MTX/PN-L nanoparticles. Comparing to other anticancer drug loaded polymeric nanoparticles reported previously [23][24][25][26][27], the release of MTX loaded polyrotaxanes nanoparticles was very fast. There were two reasons to explain this phenomenon, one was that the hydrophilicity of MTX was better than other anticancer drugs such as doxorubicin and 9-nitro-20(S)-camptothecin, which resulted faster diffusion from the nanoparticles to themedium.…”

Synthesis and evaluation of biodegradable PCL/PEG nanoparticles for neuroendocrine tumor targeted delivery of somatostatin analog

“…Some recently discovered carcinogenic and noncarcinogenic agents such as certain dietary substances, natural hormones and synthetic compounds have been proposed to stop or reverse the process of carcinogenesis to alleviate the limited efficacy and considerable toxicity of conventional chemotherapy (Morse et al, 1993), in which increasing attention has been paid to somatostatin and its analogs that have been reported to exert antineoplastic effects in a wide range of tumor types such as carcinoid, osteosarcoma, leukemia, and cancers of thyroid, breast, lung, liver, pancreas, colon, as well as gastric carcinomas (Scarpignato et al, 2001;Ain et al, 1997;Marschke et al, 1999;Setyono et al, 1987;Shan et al, 2003;Gencosmanoglu et al, 2002;Lee et al, 2002;Giannetti et al, 2000;Yuen et al, 2002;Gou et al, 2011b). Poly(ε-caprolactone) (PCL), biodegradable polyesters, is most commonly used for pharmaceutical applications.…”

Animal Models of Colorectal Cancer in Chemoprevention and Therapeutics Development

“…Additionally, it has been reported that the zebrafish expressing a truncated form of APC with either retinoic acid or a selective COX-2 inhibitor decreased -catenin in the cell. Curcumin-loaded biodegradable polymeric micelles (Cur/MPEG-PCL) has been shown to efficiently block angiogenesis in transgenic zebrafish model (Gou et al, 2011). Similarly, the incorporation of doxorubicin in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of doxorubicin in Zebrafish and has implications for CRC treatment (Lee et al, 2006).…”