<p>Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin</p>

Abstract

BackgroundCurcumin is a natural polyphenol with anti-inflammatory, chemopreventive and anticancer activity. However, its high hydrophobicity and poor bioavailability limit its medical application. The development of nanocarriers for curcumin delivery is an attractive approach to overcome its low bioavailability and fast metabolism in the liver. We synthesized a blood compatible alginate-curcumin conjugate, AA-Cur, which formed colloidally stable micelles of approximately 200 nm and, as previously shown, exerted strong cytotoxicity against mouse cancer cell lines. Here we analyze in vivo toxicity and antitumor activity of AA-Cur in two different mouse tumor models.MethodPotential toxicity of intravenously injected AA-Cur was evaluated by: i) analyses of blood parameters (morphology and biochemistry), ii) histology, iii) DNA integrity (comet assay), and iv) cytokine profiling (flow cytometry). Antitumor activity of AA-Cur was evaluated by measuring the growth of subcutaneously inoculated colon MC38-CEA- or orthotopically injected breast 4T1 tumor cells in control mice vs mice treated with AA-Cur.ResultsInjections of four doses of AA-Cur did not reveal any toxicity of the conjugate, thus indicating the safety of its use. AA-Cur elicited moderate anti-tumor activity toward colon MC38-CEA or breast 4T1 carcinomas.ConclusionThe tested conjugate of alginate and curcumin, AA-Cur, is non-toxic and safe, but exhibits limited anticancer activity.

Cytotoxic, Genotoxic and Senolytic Potential of Native and Micellar Curcumin

“…From this suspension, in which micellar structures form, curcumin can better be absorbed in the gastrointestinal tract. To overcome uptake limitations, a formulation of curcumin embedded in micelles on PEG80 basis was developed and shown to have superb uptake properties [ 21 , 22 , 23 , 42 , 43 , 44 , 45 ]. Micellar curcumin was recently also tested in a feeding study and demonstrated to be safe and effective as an anticancer agent in a colorectal mouse model [ 46 ].…”

Natural Ingredient-Based Polymeric Nanoparticles for Cancer Treatment

“…The formulation was not toxic to mouse endothelial cells nor to cells isolated from human blood, but it showed strong cytotoxicity to various cancer cell lines. In the mice model, the formulation had no toxicity, but therapeutic effects were not as significant as those in vitro [117,118]. Dextran can also be used to form micelles.…”

Hard, Soft, and Hard-and-Soft Drug Delivery Carriers Based on CaCO3 and Alginate Biomaterials: Synthesis, Properties, Pharmaceutical Applications

“…Unlike CCPs, hydrogels can be elongated or stretched under an external force to pass through narrower channels without clogging them, since they possess high plasticity determined by their softness [ 259 ]. Therefore, for intravenous injection an Alg-based drug delivery system can have a larger size than that of CCPs carriers; in this regard, some typical particles with sizes in the range of 180–400 nm have been investigated exhibiting good capabilities for carrying drugs [ 260 , 261 , 262 ]. However, that does not rule out a preference for smaller-sized Alg particles [ 263 , 264 , 265 ].…”