In vitro evaluation of the cytotoxicity of a folate-modified β-cyclodextrin as a new anti-cancer drug delivery system

Abstract

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).

Supramolecular cyclodextrin-based metal-organic frameworks as efficient carrier for anti-inflammatory drugs

“…Also, the result was similar for all of the different γ-CD-MOFs assessed: γ-KCD, γ-NaCD and γ-FeCD. This behaviour is similar to that obtained by Tofzikovskaya and collaborators [23], which assessed the cytotoxicity of γ-CDs in various cells lines and observed the absence of a toxic effect. Considering the absence of cytotoxicity, the authors expect that it is safe for medical use.…”

Folic acid-modified methotrexate-conjugated gold nanoparticles as nano-sized trojans for drug delivery to folate receptor-positive cancer cells

“…The decrease in the toxicity of MTX on healthy cells [48] through the nanocarrier system supported the usability of the drug in cancer treatment. This result was also supported by previous reports [23,49]. Imaging results showed that uptake of FA-modified nanoparticles synthesized into the cytoplasm was associated with the presence of FR [14], and supported cytotoxicity results.…”

Synthesis and potential applications of cyclodextrin-based metal–organic frameworks: a review

“…Furthermore, the safety profiles of potassium cations-γ-cyclodextrin, sodium-γ-cyclodextrin, and iron-γ-cyclodextrin were examined by the cytotoxicity test on Caco-2 and HepG2 human cells at a slightly basic pH. The result proved the absence of toxicity of potassium cations-γ-cyclodextrin, sodium-γ-cyclodextrin, and iron-γ-cyclodextrin since the cell viability did not change even when the γ-cyclodextrin-based metal–organic frameworks concentration reached 2000 µg/ml, agreeing with (Tofzikovskaya et al 2015 ). The in vitro release of sodium diclofenac after 2 h at pH 1.2 from potassium cations-γ-cyclodextrin, sodium-γ-cyclodextrin, and iron-γ-cyclodextrin were 23, 22, and 20%, respectively, clarifying the low release rate.…”

“…Notably, in pH 6.4, the sodium diclofenac release was equal for 8 h, then a noticeable increase was observed since the cumulative % of the sodium diclofenac release during 24 h were 63, 41, and 42% for iron-γ-cyclodextrin, potassium cations-γ-cyclodextrin and sodium-γ-cyclodextrin, respectively. Such behavior of iron-γ-cyclodextrin may be attributed to the higher pores volume that allows to solvent to entrain and release the drug (Tofzikovskaya et al 2015 ).…”