Computational analysis of Gefitinib and methylated-hydroxypropylated cyclodextrin inclusion complexes for the treatment of childhood malignancies

摘要

Cyclodextrins (CD) have been playing a very important role in the formulation of poorly water-soluble drugs by improving apparent drug solubility and/or dissolution. In the current study we focused on the investigation of the cytotoxic effect of cyclodextrin/Gefitinib in inclusion with three types of cyclodextrin, as well as in its inhibitory activity of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase activity using biological assays. The activity of Gefitinib and Gefitinib/ cyclodextrin were measured in pediatric neuroblastoma (NB) tumor cell lines. We have shown that CD/Gefitinib complexes are effective against neuroblastoma cells in vitro. Our studies provided a detailed picture of inclusion of Gefitinib in cyclodextrins and verify improved efficacy of the CD-encapsulated drug in cytotoxicity assays on pediatric tumor cell lines. An understanding of the structural details of guest inclusion in CDs may be useful in the engineering of modified guest-host preparations with optimized pharmacological properties and shape future therapeutic strategies.