Synthesis of TPGS/Curcumin Nanoparticles by Thin-Film Hydration and Evaluation of Their Anti-Colon Cancer Efficacy In Vitro and In Vivo

Abstract

Curcumin (CCM) has many potential uses in anticancer chemotherapy, but its low water solubility poses a major problem, preventing its translation into clinical use. TPGS is a water-soluble derivative of vitamin E that acts as a surfactant with the ability to form micellar nanoparticles in water. More importantly, TPGS acts as a potent antioxidant that can neutralize intracellular reactive oxygen species (ROS). In this study, we solubilized CCM with TPGS using thin-film rehydration to prepare aqueous formulations containing CCM at clinically relevant concentrations. We found that the minimal TPGS:CCM ratio for producing nanoparticles was 5:1 (w/w): at or above this ratio, stable nanoparticles formed with an average particle diameter of 12 nm. CCM was released from TPGS/CCM micelles in simulated colonic and gastric fluids. These TPGS/CCM nanoparticles were shown to decrease intracellular ROS levels and apoptosis and inhibited migration of HT-29 human colon cancer cells more potently than free CCM. Pharmacokinetic analysis showed TPGS/CCM to be more bioavailable than free CCM after oral administration to rats. Our results suggest that TPGS/CCM may increase therapeutic efficacy of CCM against colon cancer and merits further investigation in a clinical setting.

Ex Vivo Conjunctival Retention and Transconjunctival Transport of Poorly Soluble Drugs Using Polymeric Micelles

“…Structural results show that all systems self-aggregate in small micelles with a core shell structure; the presence of TPGS molecules helps the poloxamer with the formation of monodisperse spherical micelles. The size of the systems is in good agreement with that found in the literature for poloxamer 407 [49], TPGS [50,51] or mixed micelles [7], using microscopic techniques such as TEM or cryo-TEM.…”

Characterization of an Amphiphilic Phosphonated Calixarene Carrier Loaded With Carboplatin and Paclitaxel: A Preliminary Study to Treat Colon Cancer in vitro and in vivo

“…Nanomedicine is an emerging, dynamic branch of therapeutics that continues to gain prominence as a viable treatment alternative for many cancers, including colon cancer (Zhang Q. et al, 2019). Nanomedicine encompasses the application of nanotechnology (construction of functional structures on the nanometer scale) to the treatment, diagnosis, monitoring, and control of biological systems (Yang et al, 2015; Li et al, 2019; Wei et al, 2019). This field has seen the development of a number of drug delivery platforms, including polymer-drug conjugates (Li and Wallace, 2008; Karolczak-Bayatti et al, 2019), liposomes (Paasonen et al, 2010; Shen and Ye, 2019), micelles (Dehghan Kelishady et al, 2014; Alliot et al, 2019), nanoshells (Huschka et al, 2012; Russo et al, 2019), and dendrimers (Modi et al, 2014; Zhao et al, 2017).…”

Metal ion-responsive nanocarrier derived from phosphonated calix[4]arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage

“…Such neutralization may destabilize the micelles, accelerating release of the drug cargo. This may explain how the micelles can release drug preferentially in perihematomal tissue, where metal ion concentrations are elevated [56,57].…”