Osteosarcoma is the most common primary bone malignancy that predominantly affects children and adolescents. Curcumin is a principal substance in Asian spice turmeric has been shown to block osteosarcoma cell growth. However, clinical development of curcumin has been hindered due to poor aqueous solubility and, thus, bioavailability, restricting the use of the drug. To date, there is a firm evidence that long-circulating polymeric micelles can effectively accumulate in tumors due to microvascular permeability to circulating macromolecules and their lymphatic drainage in solid tumors. Polymeric micelles (self-assemblies) are species with hydrophilic exterior and hydrophobic interior that provide environment to accommodate water-insoluble molecules, including curcumin. The size of these assemblies, typically 10-100 nm, can be controlled by varying the length of the hydrophobic fragment in the amphiphilic polymers.<br/>In order to improve bioavailability and efficacy of the curcumin in bone tumor treatment, the drug was loaded (solubilized) into micellar assemblies made from new amphiphilic invertible polymers, (AIPs). Release profile and the anti-tumor effects of micellar polymer assemblies-mediated delivery of curcumin on osteosarcoma cell survival was evaluated. The unique ability of curcumin-loaded polymer micellar assemblies to remain stable in water but rapidly release the cargo molecules due to inverting the AIP macromolecular conformation by changing polarity of the environment was assumed to be a decisive factor in a controlled delivery and release of the curcumin to osteosarcoma cells.<br/>Obtained <i>in vitro</i> results show that polymer micellar assemblies-delivered curcumin is effective in blocking osteosarcoma cell growth. It significantly decreases cell viability in MG63, 143B and K7M2 cells compared to control. At the same time, micellar assemblies-mediated curcumin did not have any effect on normal osteoblasts. Confocal microscopic analysis shows that curcumin is readily taken up by osteosarcoma cells but not by osteoblasts suggesting that micellar polymer assemblies have specificity for tumor cells. These studies prove that polymer micellar assemblies from amphiphilic invertible polymers are effective in curcumin delivery and targeting tumor cells. This approach could be useful in the treatment of osteosarcoma.

Invertible micellar polymer assemblies for targeted delivery of curcumin to osteosarcoma cells

249th National Meeting (2015)

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