Amphiphilic Curcumin Conjugate-Forming Nanoparticles as Anticancer Prodrug and Drug Carriers: In Vitro and In Vivo Effects

Abstract

Curcumin has been shown to have high cytotoxicity towards various cancer cell lines, but its water insolubility and instability make its bioavailability exceedingly low and, thus, it is generally inactive in in vivo anticancer tests. Here, we report an intracellular-labile amphiphilic surfactant-like curcumin prodrug--curcumin conjugated with two short oligo(ethylene glycol) (Curc-OEG) chains via beta-thioester bonds that are labile in the presence of intracellular glutathione and esterase. Curc-OEG formed stable nanoparticles in aqueous conditions and served two roles--as an anticancer prodrug and a drug carrier. As an anticancer prodrug, the formed nanoparticles had a high and fixed curcumin-loading content of 25.3 wt%, and released active curcumin in the intracellular environment. Curc-OEG had high inhibition ability to several cancer cell lines due to apoptosis. Intravenously injected Curc-OEG significantly reduced the tumor weights and tumor numbers in the athymic mice xenografted with intraperitoneal SKOV-3 tumors and subcutaneous (mammary fat pad) MDA-MB-468 tumors. Preliminary systemic toxicity studies found that Curc-OEG did not cause acute and subchronic toxicities to mouse visceral organs at high doses. As drug carriers, Curc-OEG nanoparticles could carry other anticancer drugs, such as doxorubicin and camptothecin, and ship them into drug-resistant cells, greatly enhancing the cytotoxicity of the loaded drug. Thus, Curc-OEG is a promising prototype that merits further study for cancer therapy.

Development and characterization of co-loaded curcumin/triazole-halloysite systems and evaluation of their potential anticancer activity

“…Previous attempts at encapsulating curcumin in liposomes, phospholipid complexes, or other nanoparticle-based technologies have been reported, showing an improvement in water dispersibility and a longer circulation time (Tang et al, 2010;Duan et al, 2010;Kim et al, 2011) A possible nanosized delivery system is constituted by naturally available clay halloysite nanotubes (HNT). Halloysite has been found a viable and inexpensive nanoscale container for the encapsulation of biologically active molecules such as biocides and drugs, as Price et al (2001) first demonstrated.…”

Novel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells

“…Previous attempts at encapsulating curcumin in liposomes, phospholipid complexes, and other nanoparticle-based technologies have been reported, which appear to provide better water dispersibility and a longer circulation time. [10][11][12][13][14] A key attribute of an optimal drug delivery system for cancer is the ability to treat tumors effectively with minimal side effects. In addition to having good solubility in water and stability, increased drug permeability and improved antitumor activity in vivo are also important factors.…”

Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin

“…35,36 Researchers have also investigated nanoscale formulations of curcumin, such as liposomes, microemulsions, and micelles, for potential therapeutic applications. [37][38][39][40][41][42] The nanoscale effect by which such drug delivery systems improve the oral performance of curcumin involves increasing the surface area and interactions of curcumin, thereby providing better water dispersibility to enhance its absorption. 38 In this study, a novel silica-coating liposomal strategy was used to construct a nanohybrid formulation for curcumin.…”