Curcumin nanoformulations: a future nanomedicine for cancer

Abstract

Curcumin, a natural diphenolic compound derived from turmeric Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion and apoptosis, revealing its anticancer potential. In this review, we focus on the design and development of nanoparticles, self-assemblies, nanogels, liposomes and complex fabrication for sustained and efficient curcumin delivery. We also discuss the anticancer applications and clinical benefits of nanocurcumin formulations. Only a few novel multifunctional and composite nanosystem strategies offer simultaneous therapy as well as imaging characteristics. We also summarize the challenges to developing curcumin delivery platforms and up-to-date solutions for improving curcumin bioavailability and anticancer potential for therapy.

Figure 1

Types of curcumin nanoformulation used in cancer therapeutics. (a) Various types of curcumin nanoformulation developed during the past 10 years. (b) Increased use of curcumin nanoformulations during the past decade. Data were collected from journals published by Elsevier, Wiley Interscience, American Chemical Society, Springer, BMC Central and PubMed. * indicates data collected from Jan 2011 to July 2011. (c) Chemotherapeutic effects in PC-3 cancer cells of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (nanoCUR) over free curcumin (CUR) through the formation of vacuoles involving the entire cell structure, as observed under a transmission electron microscope. Abbreviation: N, nucleus. Black arrows indicate vacuoles.

Figure 2

Size-dependant absorption characteristics of drug crystals and curcumin crystal formation. (a) Large drug crystals have poor absorption properties, whereas smaller particles (micro–nanometer) result in rapid dissolution and bioavailability. (b) Curcumin drug particle formation and conversion into precipitation in a bottom-up approach in an alcohol and water mixture with time. Reprinted, with permission, from [31].

Figure 3

Improved therapeutic effects of curcumin by curcumin conjugate (PCurc8) formulation in cancer cells. (a) Cytotoxicity effect of PCurc 8 formulation in SKOV-3, OVCAR-3 and MCF-7 cancer cell lines after 72-h incubation followed by 24-h incubation in free medium. (b) Intracellular localization of curcumin conjugate observed by confocal microscopy. SKOV-3 ovarian cancer cells incubated with PCurc 8 at 25 µg/ml for 2 h (i–iii) and 24 h (iv–vi). PCurc 8 channel (green, left column) and the LysoTracker® channel (red, middle column), and overlapped channels (right column). (vi) also indicates the overlap of the nuclear dye channel with a blue color. (c) Immunoblotting with anti-cyclin D1, CDK4, CDK6 and procaspase-3 antibodies after treating cells with 10, 20 and 40 µg/ml of PCurc 8. Downregulation of CDK4 and CDK6 indicates that the SKOV-3 cells were hindered at the G0/G1 or G1 phases before going into S phase. Reprinted, with permission, from [47].

Figure 4

Schematic representation of 4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] (CLEFMA) liposomes obtained by a drug-in CD-in liposome method, detailing tumor volume control with liposomal CLEFMA treatment. Insets show representative pictures of excised tumors upon necropsy. The dashed lines are the trend lines of the plotted data. The data are presented as the mean ± SEM of results from experiments on n = 4 (treatment) and n = 3 (control) rats.Reprinted, with permission, from [99].