# Curcumin Innovative Delivery Forms: Paving the Yellow Brick Road' of Antitumoral Phytotherapy
## 4 Innovative Curcumin Formulations and High-Performance Delivery Forms
### New Injectable forms of Curcumin  
Injectable forms of curcumin are, to the best of our knowledge, currently unavailable in the market. Several parenteral formulations of curcumin are described, including the proprietary formulations named \"Lipocurc\" and \"NanoCurc\", but these are still not approved by the FDA. Lipocurc is a liposomal formulation for curcumin [186] with 100 nm mean particle size. It exhibited excellent in vitro antiproliferative activity against several pancreas cancer cell lines (ASPC-1, BxPC-3, Capan-1, Hs766-T, and MiaPaCa2), with half-maximal inhibitory concentration (IC\({}_{50}\)) values within 2-7 \(\upmu\)M, as well as tumor-reducing and anti-angiogenic effects in mice xenografted with human pancreas carcinoma (BxC-3 and MiaPaCa2) [187]. Clinical trials (phases 1a and 1b) with Lipocurc in 70 human subjects showed no cardiac toxicity and signs of efficacy in end-stage cancer patients who had failed 6-7 prior chemotherapy regimens; results of phase 2 trials should be available soon [188]. Another claimed  
\begin{table}
\begin{tabular}{c c c c c} \hline
**Trade Name** & **Formulation Strategy** & **Dosage Form** & **Product Composition** & **Ref. ** \\ \hline \multirow{4}{*}{Cavacurmin} & Cyclodextrin inclusion & & & \\  & complex & Dry powder & Cavacurmin: curcumin, \(\gamma\)-cyclodextrintrin & [179] \\  & w/ Curcumin & & & Liposome: Turmeric root extract, \\  & & 500 mg capsules & phosphatidylcholine, phospholipids \\  & & (100 mg curcumin) & Excipients: HPMC, leucine, silicon dioxide & \\  & &  
application of intravenous liposomal curcuminin is in the treatment of neurodegenerative and stress disorders, according to a patent filed in 2011 [189]. Nanocurc is a polymeric nanoparticle formulation of curcumin. The nanoparticles have an average size of 50 nm, being thus smaller than the aforementioned liposomes. They are obtained from the micellar aggregates of cross-linked, random co-polymers of N-isopropylacrylamide (NIPAAM), with N-vinyl-2-pyrrolidone (VP) and poly(ethyleneglycol)-monoacrylate (PEG-A) [190]. Nanocurc showed sustained plasma concentrations of curcumin with T\({}_{\text{max}}\) of \(2.75\pm 1.50\) h and \(C_{\text{max}}\) of \(46.62\pm 14.05\) uM and a good inhibitory effect on Pa03C (human pancreatic cancer) xenografts in mice [191]. It is able to cross the blood-brain barrier [192], which may be useful in addressing brain tumors. Curcumin-loaded biodegradable micellar nanoparticles based on a co-polymer of PEG and poly(\(\varepsilon\)-caprolactone) were developed for the treatment of colon cancer [193,194]. These particles have an average size around 28 nm, being even smaller than those of Nanocurc (described above). In vitro studies showed their direct cytotoxic effect on murine colon carcinoma cells (CT26 line) and in vivo studies on xenograft mice further confirmed the anticancer effect, associated with anti-angiogenesis. The therapeutic action and improved pharmacokinetics of curcumin carried by these micelles makes this system an excellent intravenously injectable aqueous formulation of curcumin, one that has potential clinical application in colon cancer therapy. PLGA was also used to encapsulate curcumin, both in the form of injectable microparticles [195] and of nanoparticles [196]. The curcumin microparticles had an average diameter around 22 um and featured sustained release properties over four weeks (in mice), inhibiting the growth of human breast cancer cells (MDA-MB-231 line), both in vitro and in vivo in xenograft mice treated by intraperitoneal injection. It should be stressed, however, that PLGA microparticles cause acidity and inflammatory response at the site of injection due to partial degradation to lactic and glycolic acids, even though the inflammation is attenuated by the anti-inflammatory properties of curcumin. Carrier-free injectable curcumin can also be prepared by a simple process of nanocrystalization.