A central composite design-based targeted quercetin nanoliposomal formulation: Optimization and cytotoxic studies on MCF-7 breast cancer cell lines.

This study aimed to enhance the efficacy of quercetin (QT) by formulating it into a liposomal drug delivery system utilizing the concept of central composite design. The drug:lipid ratio, cholesterol concentration, and sonication time were selected as independent variables in the study. The vesicle and percentage entrapment efficiency were selected as the dependent variables. Quercetin nanoliposomes (QT-NLs) were prepared via a combination of ethanol injection and thin film hydration. The vesicle size and entrapment efficiency of all formulations were within the ranges of 100 nm and >80 %, respectively. The zeta potential value indicated the stability of the optimized formulation. The contour plots were used to select the desired batch range. SEM studies revealed an imperfect crystalline morphology without any unwanted agglomeration. MTT assays on VERO cell lines indicated the safety of the developed formulation. MTT assays of MCF-7 cells revealed IC50 values of 5.8 µM and 7.9 µM for QT-NLs and QT, respectively. In our study, the optimized formulation exhibited late and early apoptosis and necrosis when used to treat MCF-7 cells. S and G2/M cell cycle phases of MCF-7 cell arrest were confirmed by the cell cycle report. At sub-G0/G1 phase, 2.10 ± 1.1 %; G0/G1 phase, 34.13 ± 1.9 %; S phase, 34.55 ± 0.98 %; and G2/M phase, 26.24 ± 1.7 % of cell arrest were observed. The results demonstrated the effectiveness of the proposed design for the development of corn starch-coated QT-NLs and their activity in breast cancer cell lines.

Potential preventative impact of aloe-emodin nanoparticles on cerebral stroke-associated myocardial injury by targeting myeloperoxidase: In supporting with In silico and In vivo studies.

The present study examined the potential neuroprotective effects of aloe-emodin (AE) nanoparticles on the cerebral stroke-associated target protein myeloperoxidase (MPO). We investigated the binding interactions between AE and MPO through molecular docking and molecular dynamics simulations. Molecular docking results indicated that AE exhibited a binding energy of -6.9 kcal/mol, whereas it was -7.7 kcal/mol for 2-{[3,5-bis(trifluoromethyl)benzyl]amino}-n-hydroxy-6-oxo-1,6-dihydropyrimidine-5-carboxamide (CCl). Furthermore, molecular dynamics studies demonstrated that AE possesses a stronger binding affinity (-57.137 ± 13.198 kJ/mol) than does CCl (-22.793 ± 30.727 kJ/mol), suggesting that AE has a more substantial inhibitory effect on MPO than does CCl. Despite the therapeutic potential of AE for neurodegenerative disorders, its bioavailability is limited within the body. A proposed hypothesis to enhance the bioavailability of AE is its conversion into aloe-emodin nanoparticles (AENP). The AENPs synthesized through a fabrication method were spherical with a consistent diameter of 104.4 ± 7.9 nm and a polydispersity index ranging from 0.525 to 0.586. In rats experiencing cerebral stroke, there was a notable increase in cerebral infarction size; abnormalities in electrocardiogram (ECG) and electroencephalogram (EEG) patterns; a decrease in brain and cardiac antioxidant activities; and an increase in myeloperoxidase levels compared to those in normal rats. Compared with AE treatment, AENP treatment significantly ameliorated cerebral infarction, normalized ECG and EEG patterns, enhanced brain and cardiac antioxidant activities, and reduced MPO levels in stroke rats. Histopathological evaluations revealed pronounced alterations in the rat hippocampus, with pyknotic nuclei, disarray and loosely packed cells, deterioration of cardiac muscle fibers, and extensive damage to cardiac myocytes, in contrast to those in normal rats. AENP treatment mitigated these pathological changes more effectively than AE treatment in both brain and cardiac cells. These findings support that AENP provides considerable protection against stroke-associated myocardial infarction.

Anti-Parkinson potential of hesperetin nanoparticles: in vivo and in silico investigations.

Parkinson's disease (PD) is characterised by the gradual demise of dopaminergic neurons. In recent years, there has been significant interest in herbal treatments. In this study, hesperetin nanoparticles (HTN) were developed and compared their anti-PD potential with hesperetin (HT) on rotenone induced PD rats. Molecular docking was also performed to evaluate the binding affinity of hesperetin on pathological protein, i.e. D2 dopamine receptors (DR2), using Auto Dock Vina tools. The results showed a higher binding relationship of HTN on dopamine receptors (-7.2 kcal/mol) compared to L-dopa (-6.4 kcal/mol), supporting their potential as drug candidates for PD therapy. HTN was effectively synthesised using the fabrication technique and characterised by zeta potential and SEM analysis. HTN had favourable characteristics, including a size of 249.8 ± 14.9 nm and a Z-potential of -32.9 mV. After being administered orally, HTN demonstrated a notable anti-Parkinsonian effects, indicated by the significant improvement in motor function as assessed by the rota rod test (p < .001***), pole test (p < .001***), stair test (p < .01**), wood walk test (p < .01**) and an increase in substantia nigra (SN) antioxidant levels, CAT (p < .001***), SOD (p < .001***), GSH (p < .01**). Additionally, HTN led to increased dopamine levels (p < .01**) and a decrease in the oxidant system, MDA levels (p < .01**). Furthermore, histopathological examination revealed decreased SN neuronal necrosis in diseased animals treated with HTN compared to those treated with HT in a rat model of Parkinson's disease. Therefore, HTN can be regarded as a viable platform for efficient therapy of PD.