A novel two-step synthetic route was developed and gave the mono-substituted derivative 6-deoxy-6-[(1-(2-amino)ethylamino)folate]--cyclodextrin (CDEnFA) with high yield (60 %). Elemental analysis, mass spectrometry, 1 H and 13 C NMR, FTIR and Raman spectroscopies demonstrated the successful synthesis of the γ isomer only with no evidence of the presence of other isomers or free folic acid. Electronic absorption spectroscopy was used to study the photochemical properties of CDEnFA and showed that in both the solid state and aqueous solution CDEnFA is considerably more photo-stable than free folic acid.

Many chemotherapeutic drugs are therapeutically non-selective and do not distinguish between healthy cells and tumour cells which can result in severe side effects and toxicity. Drug delivery systems can be used to target specific cells and therefore may eliminate many of the side effects, increasing drug efficiency and efficacy, and controlling drug release. One possible strategy for targeted drug delivery is to use unique molecular markers such as folate receptors in cancer cells. In this work the cytotoxicity of a novel cyclodextrin-folate conjugate, 6-deoxy-6-[(1-(-2amino)ethylamino)folate-b-cyclodextrin (CDEnFA) was studied using the MTT assay and the MCF-7 (Breast), HeLa (Cervical), A549 (Lung cancer) and BEAS-2B (normal Lung) cell lines. The MTT assay showed that the drug delivery vehicle CDEnFA is not cytotoxic towards the cell lines studied even towards the normal BEAS-2B cell line and therefore it is expected that it is safe for medical use. The inclusion complex CDEn-FA:MTX has superior cytotoxic activity towards all of the cancer cell lines studied compared to the drug MTX alone and CDEnFA:MTX is four times less cytotoxic than the drug towards the normal cell line. The observed toxicity is attributed solely to MTX since CDEnFA did not exhibit significant cytotoxicity. These results also suggest that the drug remains bioactive even after inclusion in the CD cavity. The cytotoxicity trend observed for CDEnFA:MTX in this study is [ A549 (Lung) [ HeLa (Cervical) [ BEAS-2B (normal Lung).

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