TPGS polymeric micelles for poorly soluble drug delivery

D--tocopheryl polyethylene glycol succinate 1000 (TPGS) represents a vitamin E-based water-soluble molecule, which is synthetized from the natural vitamin E esterified with succinic acid and then the obtained vitamin E succinate derivative is linked to polyethylene glycol 1000 (PEG). Also due to its natural origin, TPGS is a safe amphiphilic excipient able to self-assemble above the critical micellar concentration (CMC = 0.02% wt/wt) in micelles of about 13 nm endowed of a hydrophilic shell and a hydrophobic core, which can host poorly water-soluble drugs. On the base of these features, in the last decade, TPGS has been widely studied as permeation enhancer, emulsifier, carrier for drug delivery, and solubilizing agent. Moreover, TPGS at concentration below its CMC, can reduce the activity of the P-glycoprotein (P-gp), involved in the acquisition of multidrug resistance (MDR) in cancer cells. Resveratrol (RES) is a phytoalexin naturally produced by many plants for protective purposes, endowed with antioxidant, anti-inflammatory properties and pro apoptotic activity exploitable both in the treatment and in the prevention of cancer. On the contrary, Fenretinide (4-HPR) is a synthetic retinoid, but similarly to RES, possess cytotoxic and apoptotic activities towards cell lines of various tumor types. Unfortunately, several drawbacks such as photosensitivity, thermolability, poor water solubility, low oral absorption and hepatic "first pass" effect, do not allow both of these bioactive chemicals to reach the target sites in adequate concentration, limiting the fully exploitation of their therapeutic potentialities. To address at least some of these issues, we have herein exploited the feasibility of TPGS to encapsulate RES and separately 4-HPR, obtaining drug-loaded TPGS micelles, potentially usable for the treatment and chemoprevention of tumors