Çopur, Tuğba; Kurt, Nihat; Pezik, Esra; Yalçın, Doruk; Bozdağ Pehlivan, Sibel; Öner, Levent

The blood–brain barrier (BBB) separates blood from brain tissue, making drug delivery to the brain a significant challenge. This study aims to develop and optimize a novel nanoparticle system that may overcome the BBB and have a potential effect on glioblastoma. Ketorolac tromethamine (KT)-loaded poly(lactic-co-glycolic acid) (PLGA) RG 503-H nanoparticles were prepared using water/oil/water (W/O/W) emulsification solvent evaporation. KT-loaded nanoparticles have a particle size of 155.5 ± 2.08 nm, a zeta potential of -12.9 ± 1.23 mV, a polydispersity index of 0.111 ± 0.035, and an encapsulation efficiency of 53.46%. A significant portion of the drug (> 90%) was released in 6 h and completed within 24 h. When 3% (w/v) mannitol and trehalose were used as cryoprotectants, the nanoparticles remained physically stable. Additionally, it has been discovered that KT solution is cytotoxic at high doses to Rat Brain Glioblastoma (RG2) cells, and KT-loaded nanoparticles are more effective than drug solutions at lower doses.

Samir, Nourhan; Özerkan, Dilşad; Danışman-Kalındemirtaş, Ferdane; Kariper, İshak Afşin; Bulut, Huri; Kuruca, Dürdane Serap; Altuner, Ergin Murat; Ulukaya, Engin

Background: Green synthesis is a simple, inexpensive, and highly efficient method for the preparation of nanoparticles. In this study, ethanol extracts of Homalothecium sericeum (HOM) moss were used as reducing agents for the synthesis of biocompatible ruthenium nanoparticles (RuNPs). The ruthenium-based green synthesis method has not been used in any other work in the literature. UV–visible spectrophotometer (UV–Vis), Zetasizer, FTIR, and EDX-SEM were used to characterize the RuNPs synthesized by the green synthesis method, and their efficacy on cell viability was tested on HCT116 human colon cancer cells. Methods: UV spectroscopic measurements were used to study the release of HOM-RuNPs. Apoptosis was assessed by measuring protein expression of p53, Bax, and Bcl-2 by Western blotting. The presence of apoptosis was confirmed by double staining with Hoechst dye/propidium iodide under a fluorescence microscope. HOM-RuNPs were also tested for BCRP/ABCG2 expression to check for drug resistance. Results: HOM-RuNPs with a size of 70–80 nm were found to be most effective at a dosage of 5.71 µg/ml and induced cell death by increasing the ratio of Bax/Bcl-2 and p53 expression. It was also shown to reduce multidrug resistance protein (ABCG2), suggesting that it may be useful against multidrug resistance. Conclusion: Ruthenium-based nanoparticles synthesized by a green synthesis technique may be a candidate for anticancer drugs in the pharmaceutical industry and deserve further attention for proof-of-concept studies.

Polat, Heybet Kerem; Arslan, Aslıhan; Ünal, Sedat; Haydar, Muhammet Kerim; Aytekin, Eren; Gözcü, Sefa; Karakuyu, Nasıf Fatih; Mokhtare, Behzad

Purpose: To overcome the problems of low bioavailability of the drug associated with the short pre-corneal residence time, a thermoresponsive in situ gel system containing poloxamer P407, hydroxypropyl methylcellulose, and chitosan was developed to prolong the pre-corneal residence time of the drug. Methods: The central composite design was utilized to assess the effects of the concentration of poloxamer 407 hydroxypropyl methylcellulose and chitosan, the concentration of polymer, and the polymer type on the viscosity, pH, and gelation temperature, which were considered indicators of optimum formulations. Results: After model selection for response analysis, the quadratic model was found to be the best-fitting model for the relationship between independent factors and response variables. As a result of the central composite design, the optimized formulation contained 15.17% poloxamer 407 and 2.141% chitosan. Viscosity 25 °C = 2199.4 ± 26.2, viscosity 35 °C = 15,487.2 ± 117.4, pH = 6.5 ± 0.01, and gelation temperature °C = 33.3 ± 0.47 were obtained. The ex-vivo study revealed that the BRN formulation containing flurbiprofen-cyclodextrin inclusion complex has higher corneal penetration (P < 0.01). The cytotoxicity of ARPE-19 cells and irritation studies, as measured by in situ gel, was found to be acceptable. In lipoxygenase studies, the effectiveness of the BRN formulation was found to be significantly higher than other formulations (P < 0.01). Conclusions: It is thought that the BRN formulation may be an alternative to the treatment of ocular allergic disease.