Enhancing the Solubility of Valrubicin via Albumin and TPGS Formulations

Human serum albumin (HSA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) are versatile biocompatible materials used in drug formulation. Due to its lipophilicity, the anticancer drug valrubicin (VALSTAR) has been solubilized with Cremophor EL, a solvent known for its systemic toxicity. While valrubicin is less toxic than its widely used hydrophilic anthracycline analogues, its clinical use is currently restricted to intravesical route for bladder cancer treatment. Because preliminary studies have shown a strong affinity of valrubicin for HSA and TPGS micelles, this study was aimed to explore the potential of reduced HSA (rHSA) or TPGS as excipients for valrubicin. In an aqueous environment, valrubicin solubility was enhanced from 0.1 to 85.4% using rHSA while it was dependent upon TPGS concentration. With appropriate formulation approaches, rHSA or TPGS could serve as valrubicin transporters and could thus, enable its systemic administration and extended use beyond bladder cancer to other cancer types.