Galangin/β-Cyclodextrin Inclusion Complex as a Drug-Delivery System for Improved Solubility and Biocompatibility in Breast Cancer Treatment.
Zainab S AbbasGhassan M SulaimanMajid Sakhi JabirSalman A A MohammedRiaz A KhanHamdoon A MohammedAmal Al-SubaiyelPublished in: Molecules (Basel, Switzerland) (2022)
The purpose of this study was to evaluate the potential of a newly modified cyclodextrin derivative, water-soluble β-cyclodextrin-epichlorohydrin (β-CD), as an effective drug carrier to enhance the poor solubility and bioavailability of galangin (GAL), a poorly water-soluble model drug. In this regard, inclusion complexes of GAL/β-CDP were prepared. UV-VIS spectrophotometry, Fourier-transform infrared spectroscopy (FTIR), X-ray crystallography (XRD), zeta potential analysis, particle size analysis, field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM) were applied to characterize the synthesized GAL/β-CD. Michigan Cancer Foundation-7 (MCF-7; human breast cancer cells) and rat embryo fibroblast (REF; normal cells) were employed to examine the in vitro cytotoxic effects of GAL/β-CD using various parameters. The dye-based tests of MTT and crystal violet clearly exhibited that GAL/β-CD-treated cells had a reduced proliferation rate, an influence that was not found in the normal cell line. The cells' death was found to follow apoptotic mechanisms, as revealed by the dye-based test of acridine orange/ethidium bromide (AO/EtBr), with the involvement of the mitochondria via caspase-3-mediated events, as manifested by the Rh 123 test. We also included a mouse model to examine possible in vivo toxic effects of GAL/β-CD. It appears that the inclusion complex does not have a significant influence on normal cells, as indicated by serum levels of kidney and liver enzymatic markers, as well as thymic and splenic mass indices. A similar conclusion was reached on the histological level, as manifested by the absence of pathological alterations in the liver, kidney, thymus, spleen, heart, and lung.
Keyphrases
- induced apoptosis
- electron microscopy
- water soluble
- cell cycle arrest
- cell death
- mouse model
- breast cancer cells
- oxidative stress
- signaling pathway
- endoplasmic reticulum stress
- heart failure
- endothelial cells
- high resolution
- magnetic resonance imaging
- magnetic resonance
- emergency department
- pregnant women
- computed tomography
- risk assessment
- cell proliferation
- hydrogen peroxide
- pi k akt
- induced pluripotent stem cells
- squamous cell
- solid state
- aqueous solution