Investigation on formulation parameters of donepezil HCl loaded solid lipid nanoparticles

Abstract Donepezil-HCl is a member of the acetylcholinesterase inhibitors that is indicated for the symptomatic treatment of Alzheimer's disease (AD) and has many side effects. In this study, to reduce the side effects of Donepezil-HCl and increase the penetration of the drug through the blood-brain barrier, we aimed to design a solid lipid nanoparticle (SLN) formulation. The effects of the different formulation parameters, such as homogenization speed, sonication time, lipid and drug concentration, surfactant type and concentration, and volume of the aqueous phase, were assessed for optimization. The particle size and PDI increased with increasing lipid concentration but decreased with increasing amounts of surfactant (Tween 80) and co-surfactant (lecithin). When the homogenization rate and sonication time increased, the particle size decreased and the encapsulation efficiency increased. The optimized formulation exhibited particle size, PDI, encapsulation efficiency, and zeta potential of 87.2±0.11 nm; 0.22±0.02; 93.84±0.01 %; -17.0±0.12 mV respectively. The in vitro release investigation revealed that approximately 70% of Donepezil-HCl was cumulatively released after 24 hours. TEM analysis proved that spherical and smooth particles were obtained and formulations had no toxic effect on cells. The final optimized formulation could be a candidate for Donepezil-HCl application in Alzheimer's treatment with reduced side effects and doses for patients

Seseli petraeum M. Bieb. (Apiaceae) Significantly Inhibited Cellular Growth of A549 Lung Cancer Cells through G0/G1 Cell Cycle Arrest.

Seseli L. is an important genus of the Apiaceae family, with a large number of aromatic species. It is used in traditional medicine extensively, but there is quite limited information on their phytochemicals and biological activities. Seseli petraeum M. Bieb. grows in Northern Anatolia, and there are no phytochemical studies on this species. In the present study, we aimed to investigate the effect of the extracts of S. petraeum on A549 lung cancer cell proliferation. For this purpose, the antiproliferative effect was determined via MTT assay, and the extracts obtained from the root of S. petraeum showed a significant inhibitory effect on cell proliferation. The hexane extract of the root exhibited potent inhibition on A549 cancer cell growth at the 24th hour with 3.432 mg/mL IC50 value. The results also showed that the hexane extract had displayed cytotoxic effect through an arrest at the G0/G1 phase of the cell cycle and induced apoptosis as well as DNA damage of A549 cells. Consequently, this study demonstrated the antiproliferative potential of the extracts from S. petraeum, especially hexane extract from the roots. Further studies are required to identify the mechanisms underlying these effects.

Potentiation of the Effect of Lonidamine by Quercetin in MCF-7 human breast cancer cells through downregulation of MMP-2/9 mRNA Expression.

Combination therapies are becoming increasingly important to develop an effective treatment in cancer. Lonidamine is frequently used in cancer treatment, but it's often preferred to be used in combination with other drugs because of its side effects. In the present study, the efficacy of the combination of lonidamine with quercetin, a flavonoid of natural origin, on human MCF-7 breast cancer cells was evaluated. The results showed that the combined use of the compounds significantly increased cytotoxicity compared to administration alone (p<0.0001). In addition, while lonidamine induced a cell cycle arrest in the G2/M phase, administration of quercetin and its combination with lonidamine arrested the cell division at S point, indicating the synergistic strength of quercetin on cytotoxicity. The combination of quercetin and lonidamine significantly induced apoptosis of MCF-7 cells (p<0.0001) and increased caspase levels (p<0.0001). In this study, the combination of quercetin and lonidamine has been evaluated for the first time and the combination treatment decreased MMP-2/-9 mRNA expression more potently than the effects of the compounds alone. The results showed that lonidamine was more effective when combined with quercetin, and their combination may be a candidate for a novel strategy of treatment for breast cancer.