Erlotinib/hydroxypropyl-β-cyclodextrin inclusion complex: characterization and in vitro and in vivo evaluation

Erlotinib (ERL) is a drug used in epidermoid carcinoma treatment. One of the ERL drawbacks is low water solubility, which limits its use in the development of safer and effective formulations. The present study used the strategy of inclusion complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD) to increase the ERL water solubility, characterize the inclusion complex physico-chemically, and evaluate the in vitro cytotoxicity and in vivo antiangiogenic effect. The data showed 1:1 molar ratio ERL:HP-β-CD inclusion complex formation both in solution and in solid state. Phase-solubility analysis showed AL-type diagrams. Isothermal titrations calorimetry and nuclear Overhauser effect spectroscopy also support that formation. Despite free ERL higher cytotoxicity, higher values were associated with the complex compared with free ERL (37.5 µM), and the complex was more cytotoxic to A431 human epidermoid carcinoma cell than to osteoblasts (non-cancerous cells). In addition, the inclusion complex exhibited antiangiogenic activity without affecting the activation and recruitment of neutrophils and macrophage. Overall, these results suggest that the ERL:HP-β-CD inclusion complex could be a promising approach for developing safe and effective ERL formulation by different routes of administration.