Synthesis and Characterization of Curcumin Based Poly (β-Amino Ester) Antioxidant Nanoparticles to Control Cellular Oxidative Stress

Curcumin, an anti-oxidant obtained from the turmeric plant, has recently been gaining interest in various biological fields as it has shown effectiveness as an anti-cancerous, anti-inflammatory agent and anti-oxidant for the suppression of oxidative stress.  Oxidative stress is a pathophysiological condition defined by an increased production of reactive oxygen species (ROS, e.g.,DPPH radical, singlet oxygen (¹O₂), superoxide radicals O₂^._, peroxyl radical CCL₃O₂^.), which react with and damage cell membranes, DNA, proteins, impairing normal cellular functioning. Antioxidants, like curcumin, are capable of intercepting ROS, thereby short-circuiting the self-propagating oxidative stress state. Despite this advantage, curcumin’s poor water solubility and bioavailability makes its usage in medical applications more difficult. In order to overcome this pharmacological limitation, curcumin was conjugated with poly (β-amino-esters) (PBAE) to increase the bioavailability, and these polymers were further formulated into nanoparticles. These hydrophobic biodegradable polymeric nanoparticles are hypothesized to degrade hydrolytically within the endothelial cells and result in the release of curcumin, which in turn performs its anti-oxidant function. Degradation of nanoparticles with respect to time, cytotoxicity of nanoparticles towards the endothelial cells and their ability to prevent oxidative stress were studied in DCF florescence assays. Oxidative stress reduction effects were studied in two ways. First, degraded products of the hydrolyzed nanoparticles were introduced to the cells, and second, nanoparticles themselves were introduced to the cells.  Curcumin loaded PBAE showed effective anti-oxidant activity through hydrolytic degradation of polymer releasing free curcumin, and varying the composition of hydrophilic and hydrophobic entities in the polymer was used as a tool to optimize its degradation time.