Characterization, drug release profile and cytotoxicity of Dentatin-Hydroxypropyl-β-Cyclodextrin complex

Abstract

This current work has been conducted mainly to increase solubility and drug release properties for high hydrophobic Dentatin (DEN) by incorporation it into Hydroxypropyl-β-Cyclodextrin (HPβCD) cavity. To confirm that inclusion be succeeded, the produced complex were installed onto different machines. The latter includes: Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), and field emission-scanning electron microscopy (FE-SEM). The hydrodynamic diameter and zeta potential of DEN-HPβCD complex were 2.025 ± 0.39 nm and −33.6 mV, respectively. Ultraviolet spectroscopy was employed to further confirmation of complexation process as well as to determine drug release profile. The result showed an initial burst release (19.9% within first two minutes) and then a continuous release for an extended period of 41 h (100%). The solubility of DEN was enhanced by >300 fold following complexation when a compared to DEN alone. Moreover, MTT finding showed that this complexation did not reduce cytotoxicity of DEN after applying on prostate cancer (LNCaP), human adenocarcinoma breast cancer (MDA-MB-231) and human gastric adenocarcinoma cell line (HDT). However, further investigations are required to validate efficacy of our produced inclusion using molecular analysis and in vivo studies.

Formulation of Genistein-HP β Cyclodextrin-Poloxamer 188 Ternary Inclusion Complex: Solubility to Cytotoxicity Assessment

“…The benefit of adding the hydroxyl propyl to cyclodextrin (β-CD) is to enhance the solubilizing property (around 27 folds higher than β CD). HP-β-CD has a hydrophobic center with an outer hydrophilic surface (6.0-6.5 Å ) [18]. It is widely used to improve the solubility of poorly water-soluble drugs.…”

Inclusion complex of clausenidin with hydroxypropyl-β-cyclodextrin: Improved physicochemical properties and anti-colon cancer activity

“…These results indicate that there is an interaction between the clausenidin and the HPβCD. Ashwaq and collaborators (2017) observed the same deviation in the event related to the loss of water molecules from HPβCD, while endothermic peaks of dentatin (which is extracted from Clausena excavata ) disappeared, in the same way that occurred with the clausenidin ( Ashwaq et al, 2017 ).…”

“…The use of cyclodextrin as a strategy to increase the solubility of dentatin (isolated from Clausena excavata ) has already been described in our previous work ( Ashwaq et al, 2017 ), and different methods have been used to prepare and characterize its complexes.…”

Anticancer effect of dentatin and dentatin-hydroxypropyl-β-cyclodextrin complex on human colon cancer (HT-29) cell line

“…In a previous study, we demonstrated that DEN has pro-apoptotic properties. 11 DEN was also shown to have antimam-mary gland cancer effects in rats. 12 The anticancer effects of DEN are quite selective, it being innocuous to normal cells.…”

“… 7 – 9 DEN in a complex with hydroxy-β-cyclodextrin (HPβCD) (DEN-HPβCD) also caused growth inhibition of MDA-MB-231, LNCaP, and HGT cell lines. 11 The cancer inhibitory effect of DEN-HPβCD occurs through the induction of apoptosis, particularly by overexpressing the Bax proteins. 9 In cancer cells, DEN directly acts on the mitochondria to release cytochrome c. 6 , 7 The incorporation of lipophilic compounds into the HPβCD cavity does not only improve their water solubility while in complexation but also enhances therapeutic effects.…”