One‐Step Microfluidic Coating of Phospholipid Microbubbles with Natural Alginate Polymer as a Delivery System for Human Epithelial Lung Adenocarcinoma
Esra Ilhan‐Ayisigi, Pelin Saglam‐Metiner, Giuliana Manzi, Katharine Giannasi, Wim van Hoeve, Ozlem Yesil‐Celiktas
In this study, the neoplastic drug frequently used in the treatment of lung cancer, carboplatin is loaded to microbubbles via a microfluidic platform. In order to increase the drug loading capacity of microbubbles, carboplatin is encapsulated into alginate polymer layer. The phospholipid microbubbles (MBs) are synthesized by MicroSphere Creator, which is connected with T‐junction and micromixer for the treatment with CaCl2 solution to provide gelation of the alginate coated phospholipid microbubbles (AMBs). The carboplatin loaded alginate coated phospholipid microbubbles (CAMBs) result in 12.2 ± 0.21 µm mean size, obtained by mixing with 0.05% CaCl2 using T‐junction. The cytotoxic activities of the synthesized MBs, AMBs, and CAMBs are also investigated with the 3‐(4,5‐Dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) (MTT) and live/dead fluorescent dying assays in the A549 and BEAS‐2B cell lines. The one‐step microfluidic coating of lipid microbubbles with natural alginate polymer appears to be a promising strategy for enhanced drug reservoir properties.
Nano‐vesicular formulation of propolis and cytotoxic effects in a 3D spheroid model of lung cancer
Esra Ilhan‐Ayisigi, Fulden Ulucan, Ecem Saygili, Pelin Saglam‐Metiner, Sultan Gulce‐Iz, Ozlem Yesil‐Celiktas
Propolis exhibits therapeutic properties due to the presence of phenolic acids, esters, and flavonoids. The scope of this study was to develop a nano‐vesicular formulation and establish a three‐dimensional (3D) spheroid model in which lung cancer is recapitulated.
3D bioprinting: A powerful tool to leverage tissue engineering and microbial systems
Ecem Saygili, Asli Aybike Dogan-Gurbuz, Ozlem Yesil-Celiktas, Mohamed S Draz
Bioprinting covers the precise deposition of cells, biological scaffolds and growth factors to produce desired tissue models. The main focus of bioprinting is the creation of functional three-dimensional (3D) biomimetic composites for various application areas. Successful creations of model tissues depend on certain parameters such as determination of optimum microenvironment conditions, selection of appropriate scaffold, and cell source. As the cell culture-based assays have vital roles in the biomedical field, bioprinted tissue analogs would provide unprecedented chances to study, screen, and treat diseases. Today’s 3D bioprinting technology is able to print cells and scaffolds simultaneously, which provides the opportunity for disease modeling. This paper presents a general overview of the current state of the art in bioprinting technologies and potential 3D cell culture systems now being developed to model microbial infections, host-pathogen interactions, niches for microbiota, biofilm formation, and assess microbial resistance to antibiotics.
A hepatocellular carcinoma–bone metastasis-on-a-chip model for studying thymoquinone-loaded anticancer nanoparticles
Fatemeh Sharifi, Ozlem Yesil-Celiktas, Aslihan Kazan, Sushila Maharjan, Saghi Saghazadeh, Keikhosrow Firoozbakhsh, Bahar Firoozabadi, Yu Shrike Zhang
We report the development of a metastasis-on-a-chip platform to model and track hepatocellular carcinoma (HCC)–bone metastasis and to analyze the inhibitory effect of an herb-based compound, thymoquinone (TQ), in hindering the migration of liver cancer cells into the bone compartment. The bioreactor consisted of two chambers, one accommodating encapsulated HepG2 cells and one bone-mimetic niche containing hydroxyapatite (HAp). Above these chambers, a microporous membrane was placed to resemble the vascular barrier, where medium was circulated over the membrane. It was observed that the liver cancer cells proliferated inside the tumor microtissue and disseminated from the HCC chamber to the circulatory flow and eventually entered the bone chamber. The number of metastatic HepG2 cells to the bone compartment was remarkably higher in the presence of HAp in the hydrogel. TQ was then used as a metastasis-controlling agent in both free form and encapsulated nanoparticles, to analyze its suppressing effect on HCC metastasis. Results indicated that the nanoparticle-encapsulated TQ provided a longer period of inhibitory effect. In summary, HCC–bone metastasis-on-a-chip platform was demonstrated to model certain key aspects of the cancer metastasis process, hence corroborating the potential of enabling investigations on metastasis-associated biology as well as improved anti-metastatic drug screening.
Quantitative determination of H2O2 for detection of alanine aminotransferase using thin film electrodes
Ecem Saygili, Beyza Orakci, Melisa Koprulu, Alper Demirhan, Esra Ilhan-Ayisigi, Yalin Kilic, Ozlem Yesil-Celiktas
The abnormal concentrations or absence of biomolecules (e.g., proteins) in blood can further be used in diagnosis of a particular pathology at an early stage. Current studies are intensely focusing on the analysis of interaction and detection of biomolecules via point-of-care systems (POCs), allowing miniaturized and parallelized reactions, simultaneously. Recent developments have shown that the collaboration of electrochemical sensing techniques and POCs to overcome challenging problems in health-care settings provides new approaches in diagnosis and treatment of diseases. The aim of this study was to adapt the alanine aminotransferase (ALT) enzyme to the platinum (Pt) thin film electrode system and quantitatively determine the enzyme levels via enzymatically generated H2O2 with differential pulse voltammetry (DPV). A simple potentiostat architecture with expanded sweep range utilizing dual LMP91000 devices was developed and adapted to the needs of the biosensor. In order to calibrate the system, known concentrations of H2O2 were also tested. Moreover, signals associated with the other electroactive species coming from the ALT reaction were eliminated. Resulted potential range has been achieved between +500 mV and +900 mV and the linear range was found to be 0.05 M–0.5 M for H2O2, whereas 5 UL^−1 to 120 UL^−1 for ALT enzyme.
A novel subcritical fucoxanthin extraction with a biorefinery approach
Bahar Aslanbay Guler, Irem Deniz, Zeliha Demirel, Ozlem Yesil-Celiktas, Esra Imamoglu
Eco-friendly, cost efficient and effective extraction methods have become significant for the industries applying zero waste principles. The two main objectives of this study were; to examine fucoxanthin extraction from wet Phaeodactylum tricornutum using subcritical fluid extraction and to characterize the residual biomass in order to determine the potential application areas. The highest fucoxanthin yield of 0.69 ± 0.05 mg/g wet cell weight was achieved using methanol with solvent-to-solid ratio of 200:1 at 120 rpm, 20 MPa pressure and at 35 °C for 60 min by subcritical extraction. Microscopy images showed that most of the cells were disrupted and intracellular components were effectively released. Based on the results of energy dispersive spectroscopy, biomass contained a mixture of organic molecules including mainly carbon (57–72%), oxygen (26–41%), magnesium (0.6–1.4%) and silica (0.4–1%) (wt%). These results make the residual biomass a potential candidate for various areas such as bioenergy, material sciences and sensor technologies.
Halil Koyu, Aslihan Kazan, Ayse Nalbantsoy, Husniye Tansel Yalcin, Ozlem Yesil-Celiktas
Different parts of Prunus persica as fruits, flowers, leaves and kernels have been consumed with dietary and therapeutic purposes traditionally. During fruit production, remarkable amount of leaves which can hold important bioactive groups as phenolics, have been left unutilized. The aim of this study was to investigate cytotoxic, antimicrobial and nitric oxide inhibitory activities of supercritical carbondioxide extracts of Prunus persica leaves. Among studied cell lines, supercritical carbon dioxide extract which was processed at 150 bar, 60 °C, and 6% co-solvent ethanol, exhibited remarkable cytotoxic activity against HeLa, MPanc-96 and MCF-7 cell lines with IC50 values of 12.22 µg/ml, 28.17 µg/ml and 35.51 µg/ml respectively, whereas IC50 value of conventional solvent extract was above 50 µg/ml. Minimum inhibitory concentration values determined for antibacterial and antifungal activities against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium and Candida albicans were found as 62.50 µg/ml. Strong nitric oxide inhibition was achieved with IC50 of 9.30 µg/ml. The promising results revealed that Prunus persica leaves may have remarkable potential as supplement both for drug and food industries. This study is the first report revealing cytotoxic, antimicrobial and nitric oxide inhibitory activity of supercritical carbon dioxide extract of Prunus persica leaves.