Paclitaxel/β-CD-g-PG inclusion complex: An insight into complexation thermodynamics and guest solubility

Abstract

Paclitaxel as one of the most effective anticancer drugs has low aqueous solubility. This inevitably reveals its commercial formulation in Cremophor EL®/ethanol mixture. However, this formulation leads to several severe side effects such as hypersensitivity reactions, neurotoxicity and nephrotoxicity. Inclusion complexation has been introduced as a practical approach in increasing paclitaxel aqueous solubility. To this end, a hybrid nanocarrier system based on hyperbranched polyglycerol and β-cyclodextrin is designed with key components uniquely structured at nanoscale and evaluated according to medical requirements. Paclitaxel is included in the hydrophobic cavity of cyclodextrin as guest and was examined using isothermal titration calorimetry to determine the thermodynamic parameters of complexation. It is shown that the inclusion complex process between paclitaxel and β-CD-g-PG is entropy driven. The results revealed a significant enhancement in paclitaxel aqueous solubility, which is a key challenge in current cancer therapy.