Browsing by Author "Denkbas, Emir Baki"

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Biosynthesis of Metallic Nanoparticles: A Comparative Optimization Study for Plant Leaf Extracts and Their Biological Assays
(2016) Korpe, Didem Aksoy; Iseri, Ozlem Darcansoy; Duman, Memed; Denkbas, Emir Baki; Sahin, Feride Iffet; Haberal, Mehmet; 0000-0002-2616-6733; 0000-0001-7308-9673; 0000-0002-3462-7632; B-9957-2014; AAC-7232-2020; AAJ-8097-2021
Chondrogenesis of human mesenchymal stem cells by microRNA loaded triple polysaccharide nanoparticle system
(2019) Celik, Ekin; Bayram, Cem; Denkbas, Emir Baki; 31147048
Degenerative cartilage is the pathology of severe depletion of extracellular matrix components in articular cartilage. In diseases like osteoarthritis, misregulation of microRNAs contributes the pathology and collectively leads to disruption of the homeostasis. In this study chondroitin sulfate/hyaluronic acid/chitosan nanoparticles were prepared and successfully characterized chemically and morphologically. Results demonstrated higher chondroitin sulfate amounts led smaller nanoparticles, but lower surface zeta potential due to high electronegativity. After optimization of chondroitin sulfate amounts regarding size and charge, nanoparticles were loaded with microRNA-149-5p, a therapeutic miRNA downregulated in osteoarthritis, and evaluated focusing on their loading efficiency, release behaviour, cytotoxicity and gene transfection efficiency in vitro. Results showed all nanoparticle formulations were non-toxic and promising gene delivery agents, due to increased levels of microRNA-149-5p and decreased mRNA levels of microRNA's target, FUT-1. Highest gene transfection efficiency was obtained with the nanoparticle formulation which had the highest chondroitin sulfate load and smallest size. In addition, owing to their high chondroitin sulfate cargo, all nanoparticles were reported to enhance chondrogenesis, which was demonstrated by gene expression analysis and sulfated glycosaminoglycan (sGAG) staining. The obtained data suggest that the delivery of microRNA-149-5p via polysaccharide based carriers could achieve collaborative impact in cartilage regeneration and have a potential to enhance osteoarthritis treatment.
Designing siRNA-conjugated plant oil-based nanoparticles for gene silencing and cancer therapy
(2019) Anilmis, Nur Merve; Kara, Goknur; Kilicay, Ebru; Hazer, Baki; Denkbas, Emir Baki; 31509450
In this study, the anticancer activities of two siRNA carriers were compared using a human lung adenocarcinoma epithelial cell line (A549). Firstly, poly(styrene)-graft-poly(linoleic acid) (PS-g-PLina) and poly(styrene)-graft-poly(linoleic acid)-graft-poly(ethylene glycol) (PS-g-PLina-g-PEG) graft copolymers were synthesized by free-radical polymerization. PS-PLina and PS-PLina-PEG nanoparticles (NPs) were prepared by solvent evaporation method and were then characterized. The size was found as 150 +/- 10 nm for PS-PLina and 184 +/- 6 nm for PS-PLina-PEG NPs. The NPs were functionalized with poly(l-lysine) (PLL) for c-myc siRNA conjugation. siRNA entrapment efficiencies were found in the range of 4-63% for PS-PLina-PLL and 6-42% for PS-PLina-PEG-PLL NPs. The short-term stability test was realised for 1 month. siRNA release profiles were also investigated. In vitro anticancer activity of siRNA-NPs was determined by MTT, flow cytometry, and fluorescence microscopy analyses. Obtained findings showed that both NPs systems were promising as siRNA delivery tool for lung cancer therapy.
Development of Electrochemical Biosensor Platforms for Determination of Environmental Viral Structures
(2022) Ekici, Rumeysa; Bozdogan, Betul; Denkbas, Emir Baki
Infectious diseases caused by viruses (such as influenza, Zika, human immunodeficiency, Ebola, dengue, hepatitis, and COVID-19 virus) are diseases that have been on the agenda of the whole world for the last quarter of a century and have become one of the most important problems for people. Urgent identification of the people infected with a disease will allow these people who have contracted the disease to be treated effectively. In this context, the polymerase-chain-reaction (PCR)-based methods have been the most common and widely used method that responds with sensitivity. However, due to some disadvantages encountered in PCR applications (in particular, the test protocol is comprehensive, not fast in terms of time, not economical, requires user expertise, is not suitable for field/on-site measurements, etc.), a new generation (which can give fast results, are economical, sensitive, suitable for on-site application, etc.) of systems that can provide solutions are needed. On the subject of different test-diagnostic applications used in a large number of test-based analysis methods and techniques, electroanalytical systems have some advantages. Within the scope of this presentation, low-cost, miniaturized electrochemical platforms for surface-printed electrodes by using appropriate biochemical and viral structures of the electrode surfaces decorated with suitable agents are explained. These platforms can be used in the determination of some particular viral proteins for the understanding of viral pathogenic diseases. In this study, a copper-modified graphite electrode was developed and characterized with SEM. Afterwards, an antibody of the N protein of COVID-19 was decorated surrounding this electrode to measure the amount of that protein in the samples. The square wave voltammetry (SWV) technique was used for the electrochemical detection of SARS-CoV-2. When the results of the analyses were examined, the best analytical sensitivity and linearity were obtained by incubating the antibody-modified electrode and virus antigen for 10 min. The measurements showed linearity with a high correlation coefficient (R-2 = 0.9917). The detection limit (LOD) was calculated as 508 pg/mL. The measurement limit (LOQ) was calculated as 1.54 ng/mL. With the pencil tip, which is an easily accessible material for the modified electrode system we designed, a very precise measurement was provided for the rapid detection of the N protein of the SARS-CoV-2 virus at very low concentrations.
Development of novel poly-l-lysine-modified sericin-coated superparamagnetic iron oxide nanoparticles as siRNA carrier
(2021) Kara, Goknur; Malekghasemi, Soheil; Ozpolat, Bulent; Denkbas, Emir Baki
Small interfering RNA (siRNA) is a promising therapeutic modality, however, its successful clinical application is still challenging due to the lack of safe and efficient carrier systems. Superparamagnetic iron oxide nanoparticles (SPIONs)-based drug or gene carrier systems have displayed tremendous promise in nanomedicine. They possess intrinsic unique superparamagnetism that provides them to be concentrated in the targeted therapeutic site of action where an external magnetic field is applied. SPIONs can be also designed as theranostic agents to achieve simultaneous therapeutic and diagnostic purposes. Despite these favorable features, SPIONs are colloidally unstable and can be easily eliminated in the circulation. More importantly, the toxicological concerns associated with SPIONs, which often lead to the generation of reactive oxygen species (ROS), need to be thoroughly considered. Various types of polymers have been proposed so far to cover the surface of SPION to overcome these disadvantages. Silk protein, sericin can be ideal as a coating material due to its high biocompatibility, good biodegradability, and in vivo stability. In terms of the development of SPIONs as siRNA carriers, to the best of our knowledge, no protein was used as the coating material, and SPIONs coated with sericin have not been reported in the literature as a drug or gene carrier system.
Effect of argon plasma and Er:YAG laser on tensile bond strength between denture liner and acrylic resin
(2020) Yildirim, Arzu Zeynep; Unver, Senem; Mese, Ayse; Bayram, Cem; Denkbas, Emir Baki; Cevik, Pinar; 33039186
Statement of problem. The separation of a denture liner from the denture base can be a clinical problem. Different surface treatments to increase the bond have been evaluated, but studies comparing the effect of argon plasma and erbium-doped yttrium aluminum garnet (Er:YAG) laser on the bond between acrylic resin and a denture liner are lacking. Purpose. The purpose of this in vitro study was to evaluate the effect of argon plasma and Er:YAG laser treatments on the bond strengths of acrylic resin to 2 denture liners. Materials and methods. Heat-polymerized acrylic resin (Acron Duo) was bonded to silicone soft-liner materials (Molloplast B, n=30; Mollosil, n=30) to create control specimens (n=10), argon plasma treatment (n=10), and Er:YAG laser treatment (n=10). Silicone liners were polymerized on resin specimens. The tensile bond strength test was performed with a crosshead speed of 10 mm/min with a 10-N load until failure. Data were analyzed by using the Kruskal-Wallis test and unpaired t test (alpha=.05). Results. The laser group showed significantly higher bond strength than the argon plasma group for both Molloplast-B (P=.001) and Mollosil (P<.001). The highest tensile bond strength values were determined in the laser-treated Molloplast-B group (1.325 +/- 0.119 MPa) while the lowest bond strength values were determined in the Mollosil control group (0.384 +/- 0.018 MPa). Conclusions. Argon plasma and Er:YAG laser applications increases the tensile bond strength between soft-liner material and resin. Er:YAG laser treatment results in higher bond strength values than treatment with argon plasma for 1 minute.
Electrospun Nanofiber Reinforcement of Dental Composites with Electromagnetic Alignment Approach
(2016) Uyar, Tansel; Cokeliler, Dilek; Dugan, Mustafa; Kocum, Ismail Cengiz; Karatay, Okan; Denkbas, Emir Baki; https://orcid.org/0000-0001-5215-8887; 26952482; U-7861-2018; I-4296-2019
Polymethylmethacrylate (PMMA) is commonly used as a base acrylic denture material with benefits of rapid and easy handling, however, when it is used in prosthetic dentistry, fracturing or cracking problems can be seen due to the relatively low strength issues. Besides, acrylic resin is the still prominent material for denture fabrication due to its handy and low cost features. Numerous proposed fillers that are used to produce PMMA composites, however electrospun polyvinylalcohol (PVA) nanofiber fillers for production of PMMA composite resins are not studied as much as the others. The other focus of the practice is to compare both mechanical properties and efficiency of aligned fibers versus non-aligned PVA nanofibers in PMMA based dental composites. Field controlled electrospinning system is manufactured and provided good alignment in lab scale as one of contributions. Some novel auxiliary electrodes in controlled structure are augmented to obtain different patterns of alignment with a certain range of fiber diameters. Scanning electron microscopy is used for physical characterization to determine the range of fiber diameters. Non-woven fiber has no unique pattern due to chaotic nature of electrospinning process, but aligned fibers have round pattern or crossed lines. These produced fibers are structured as layer-by-layer form with different features, and these features are used in producing PMMA dental composites with different volume ratios. The maximum flexural strength figure shows that fiber load by weight of 0.25% w/w and above improves in the maximum level. As a result, mechanical properties of PMMA dental composites are improved by using PVA nanofibers as a filler, however the improvement was higher when aligned PVA nanofibers are used. The maximum values were 5.1 MPa (flexural strength), 0.8 GPa (elastic modulus), and 170 kJ/m(3) (toughness) in three-point bending test. In addition to the positive results of aligned and nonaligned nanofibers it was found that they both have a non-toxic feature. (C) 2016 Elsevier B.V. All rights reserved.
İşitme ve görme engellilere deri üzerinden ısıl uyartımlarla bilgi aktarımı için sistem tasarımı
(Başkent Üniversitesi Fen Bilimleri Enstitüsü, 2020) Vulga, Selin; Denkbas, Emir Baki
İletişim, hayatın devamlılığı için temel ihtiyaçlarımızdan biridir. İletişim kanallarından herhangi birinde bir engeli bulunan kişi hayata katılmakta zorluk çekmekteyken, iletişimde en aktif kullanılan duyulardan işitme ve görmenin her ikisinde engeli bulunan birey için iletişim neredeyse imkansız hale gelmektedir. Bu durum kişinin bireysel özgürlüğüne de bir engel getirmektedir. Bu durumun önüne geçmek ve kişilere iletişim özgürlüklerini geri vermek için dokunsal sistemler geliştirilmektedir. Bu tez çalışmasında işitme ve görme engelli insanlar için soğuk uyartımlar kullanarak bilgi aktarımını gerçekleştiren bir sistem tasarımı üzerinde çalışılmıştır. İnsan vücudu sürekli uyaranlara karşı bir süre sonra tepkisini azaltmaktadır. Dokunsal duyuların ortak özelliği olan bu durum adaptasyon olarak adlandırılır. Soğuk uyartımların tercih edilme sebebi adaptasyon sürecinin uzun olmasıdır. Bunun yanında literatürde, dokunsal sistemlerde soğuk uyartım üzerine yapılmış bir çalışma bulunmamaktadır. Özel engelli alfabeleri dışında her dilin harflerine göre kodlanabilecek, daha önce kullanılmayan ikilik tabanda bir kodlama sistemi geliştirilmiştir. Uyarıcılar olarak kullanılan termoelektrik modüller (peltierler), bir elin üstünde 5 parmağın proksimal kısımlarına yerleştirilmiştir. Girilen metnin harf analizini gerçekleştiren yazılım, uyarıcıların ikili kodlara (0-1) göre soğuk uyartım gönderimini kontrol etmektedir. Algılanabilen maksimum frekans değeri 2 Hz olarak belirlenmiş ve deneylerde bu değer aktarım frekansı olarak kullanılmıştır. 10 sağlıklı denek üzerinde gerçekleştirilen çalışmalar sonucunda %80’lik bir algılama doğruluğu saptanmıştır. Frekansın kişiye göre ayarlanabilir olması, engelli kişilerin algılarının daha gelişmiş olması, sisteme alışma sürecinin iyileştirilmesi ve donanım üzerinde yapılacak çalışmalar bu algılama doğruluğunu artıracaktır. Communication is one of fundamental need for the persistence of life. Even if one of the communication channels is impaired, people that own this disability have difficulties to join life. If the audio and visual channel which are the most active communication ways have defect the communication is nearly impossible. This situation is an obstacle for individual independence. For covering the situation and giving back the independence to this people, tactile systems are being developed. In this thesis, the system design that transfer information with cold stimuli for the people who are hearing and visually impaired was studied. Human body decrease the reaction to the continues stimulation. This situation is called adaptation that is the common property for tactile senses. The reason that selecting the cold stimuli is adaptation time is long. Also there is no study with the cold stimuli in the literature. Besides special alphabet for disabled people, a new alphabet that could encrypting to all language to binary system. Thermoelectric modules (peltiers) that have used as actuators are placed on the proximal area on the 5 fingers. Software analyzes the input text, controls the stimulis according to binary code. The maximum detectable frequency is determined as 2 Hz and it is used in experiments. Results of the experiments that perform on the 10 healthy voluntary subjects is about %80 accuracy of the detection. Frequency can be adjusted according to the person, the perception of disabled people is improved, the process of getting used to the system and the studies on the hardware that all will increase this perception accuracy.
Magnetic Gelatin Nanoparticles As A Biocompatible Carrier System for Small Interfering RNA in Human Colorectal Cancer: Synthesis, Optimization, Characterization, and Cell Viability Studies
(2022) Selimovic, Amina; Kara, Goknur; Denkbas, Emir Baki
Iron oxide-based nanoparticles have gained tremendous attention in developing next-generation personalized medicine modalities. Gelatin can be a good alternative for encapsulating iron oxide nanoparticles with its biocompatibility, biodegradability, low immunogenicity, and richness of functional groups. Herein, magnetic iron oxide nanoparticles (MNPs) were synthesized, coated with gelatin (Gel-MNPs), and loaded with mammalian target of rapamycin (mTOR)-silencing siRNA to induce the in vitro therapeutic effect in colorectal cancer (CRC) cells. To the best of our knowledge, this study is the first report using Gel-MNPs as siRNA carriers. We first optimized several experimental conditions for the preparation of MNPs and Gel-MNPs and the resulting opti-mized nanoparticles showed a narrow size and size distribution. Gelatin-coating increased the storage stability by preventing the aggregation of MNPs and did not alter the magnetic characteristics of MNPs significantly. siRNA encapsulation abilities of Gel-MNPs were determined in the range of 18.4% and 41.5% in varying siRNA amounts. Bare Gel-MNPs were highly cytocompatible against CRC cells, Caco-2, while Gel-MNPs-mTOR-siRNA exhibited a significant anticancer effect to kill these cells. Comparison with HiPerFect, a commercial siRNA transfection reagent, demonstrated that Gel-MNPs-mTOR-siRNA inhibited cell viability almost similar to or better than HiPerFect-mTOR-siRNA. Taken together, our data indicated that Gel-MNPs could potentially be used in further gene silencing approaches as a safe and multifunctional siRNA carrier candidate.
Magnetically responsive, sorafenib loaded alginate microspheres for hepatocellular carcinoma treatment
(2020) Alpdemir, Sukran; Vural, Tayfun; Kara, Goknur; Bayram, Cem; Haberal, Erdem; Denkbas, Emir Baki; 0000-0003-2788-550X; 33010138; ABC-8833-2020
This study aimed to develop sorafenib loaded magnetic microspheres for the treatment of hepatocellular carcinoma. To achieve this goal, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesised and encapsulated in alginate microspheres together with an antineoplastic agent, sorafenib. In the study, firstly SPIONs were synthesised and characterised by dynamic light scattering, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. Then, alginate-SPIONs microspheres were developed, and further characterised by electron spin resonance spectrometer and vibrating sample magnetometer. Besides the magnetic properties of SPIONs, alginate microspheres with SPIONs were also found to have magnetic properties. The potential use of microspheres in hyperthermia treatment was then investigated and an increase of about 4 degrees C in the environment was found out. Drug release studies and cytotoxicity tests were performed after sorafenib was encapsulated into the magnetic microspheres. According to release studies, sorafenib has been released from microspheres for 8 h. Cytotoxicity tests showed that alginate-SPION-sorafenib microspheres were highly effective against cancerous cells and promising for cancer therapy.
MiR-329 mimic based nano-therapy inhibits growth and progression of triple negative breast cancer
(2020) Kara, Goknur; Kahraman, Nermin; Denkbas, Emir Baki; Calin, George; Ozpolat, Bulent
Porous polyurethane film fabricated via the breath figure approach for sustained drug release
(2019) Daha, Gizem; Bayram, Cem; Bozdogan, Betuel; Denkbas, Emir Baki
The breath figure (BF) method is an effective process for fabricating porous polymeric films. In this study, we fabricated porous polymer films from thermoplastic polyurethane (PU) through static BF with CHCl3 as a solvent under 55-80% relative humidity. The porous PU films were prepared within various pore structures and sizes, which were adjustable, depending on the fabrication conditions. The humidity and exposure time were examined as variable parameters affecting the surface morphology, wettability, and cytotoxicity. Atorvastatin calcium, a hyperlipidemic agent, was loaded into the porous films during the casting process, and the drug-loading and drug-releasing behaviors of the porous PU membranes were evaluated. Approximately 60-80% of the drug was released in 14 days. The films exhibited sustained drug-release performances because of the hydrophobicity and nonbiodegradable nature of PU for perivascular drug administration. (c) 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47658.
Potent bioactive bone cements impregnated with polystyrene-g-soybean oil-AgNPs for advanced bone tissue applications
(2019) Ilhan, Elif; Karahaliloglu, Zeynep; Kilicay, Ebru; Hazer, Baki; Denkbas, Emir Baki
Postoperative infection in orthopaedic and trauma surgery is one of the most feared complications. Recently, the high prevalence of multidrug-resistant bacteria has made the antibiotic treatment ineffective; thus novel non-antibiotic alternative approaches to this problem are urgently needed. Based on these expectations, in this work, in order to enhance the cytocompatibility and antibacterial performances of poly (methyl methacrylate (PMMA) and beta-tricalcium phosphate (beta-TCP) bone cements were impregnated with polystyrene (PS)-g-soybean oil graft copolymer containing AgNPs (PS-Agsbox), and we assessed the antimicrobial activity of the fabricated bone cements against Staphylococcus aureus and Escherichia coli. Nanoparticles at concentration of 1.25% (5 beta-TCP) w/w in beta-TCP bone cements were able to inhibit pathogens growth, while a concentration of 3.75% (15PMMA) was needed for PMMA bone cement. Therefore, the impregnated bone cements with PS-AgsboxNPs may be further explored as an alternative antimicrobial therapy for the treatment of infected bone defects.
Preparation and characterization of novel albumin-sericin nanoparticles as siRNA delivery vehicle for laryngeal cancer treatment
(2019) Yalcin, Eda; Kara, Goknur; Celik, Ekin; Pinarli, Ferda Alpaslan; Saylam, Guleser; Sucularli, Ceren; Ozturk, Serhat; Yilmaz, Esin; Bayir, Omer; Korkmaz, Mehmet Hakan; Denkbas, Emir Baki; 31066619
Small interfering RNA (siRNA)-based gene silencing strategy has high potential on suppressing specific molecular targets, involved in cancer progression. However, the lack of an effective nanocarrier system that safely delivers siRNA to its target still limits the clinical applications of siRNA. This study aimed to develop albumin-sericin nanoparticles (Alb-Ser NPs) as a novel siRNA delivery system for laryngeal cancer treatment. Nanoparticle formulations composed of albumin and sericin at different ratios (1:1, 2:1, 1:2 w/w) were synthesized by desolvation method. The nanoparticles were modified with poly-L-lysine (PLL) for siRNA binding and decorated with hyaluronic acid (HA) to target laryngeal cancer cell line, Hep-2. HA/PLL/Alb-Ser NPs were individually loaded with siRNAs for casein kinase 2 (CK2), Absent, Small, or Homeotic-Like (ASH2L), and Cyclin D1 genes, which are overexpressed in Hep-2 cells. Downregulation of genes was confirmed by real-time PCR (RT-PCR). Size, morphological, and thermogravimetric characterizations revealed that Alb-Ser NPs having 2:1 (w/w) ratio are the most optimized formulation. Between 36.8 and 61.3% of siRNA entrapment efficiencies were achieved. HA/PLL-siRNA/Alb-Ser (2:1) NPs-mediated gene silencing resulted in a significant inhibition of cell growth and induction of apoptosis in cells. Our findings showed that HA/PLL/Alb-Ser (2:1) NPs were promising as a siRNA carrier.
The preparation of chitosan membrane improved with nanoparticles based on unsaturated fatty acid for using in cancer-related infections
(2020) Kizaloglu, Abdullah; Kilicay, Ebru; Karahaliloglu, Zeynep; Hazer, Baki; Denkbas, Emir Baki
This study includes the design of a chitosan membrane decorated with unsaturated fatty acid-based carrier system for cancer treatment and antibacterial application. For this, polystyrene-graft-polyoleic acid-graft-polyethylene glycol was prepared by free radical polymerization and characterized. Nanoparticles and caffeic acid-loaded nanoparticles were prepared by solvent evaporation technique and optimized. The short-term stability of nanoparticles was investigated at 4 degrees C. Drug encapsulation and loading efficiency were evaluated. The chitosan membrane and caffeic acid-loaded nanoparticles embedded into chitosan membrane were fabricated. The caffeic acid loaded nanoparticles embedded into chitosan membrane showed controlled release. The mechanical properties of all samples were investigated. The caffeic acid-loaded nanoparticles embedded into chitosan membranes indicated excellent antibacterial properties against theEscherichia coliandStaphylococcus aureus. The anticancer activity of all the samples was evaluated against SaOS-2 human primary osteogenic sarcoma and MC3T3-E1 pre-osteoblast cell lines by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, the flow cytometry and double staining methods. As a result, the designed carrier system showed great potential to cancer-associated infections treatment in bone cancer cases.
Silencing of survivin and cyclin B1 through siRNA-loaded arginine modified calcium phosphate nanoparticles for non-small-cell lung cancer therapy
(2020) Kara, Goknur; Parlar, Ayhan; Cakmak, Melike Cokol; Coko, Murat; Denkbas, Emir Baki; Bakan, Feray; 32956996
With the development of nanotechnology, various drug delivery systems including inorganic nanoparticles, liposomes, polymers, etc. have been developed over the past decade. Some of these nanoparticles are also forthcoming candidates for the successful delivery of small interfering RNA (siRNA) for targeted gene silencing. Upon its discovery, siRNA was perceived as a highly promising agent in the treatment of various diseases. However, it could not exhibit the expected clinical outcomes owing to the unfavorable challenges during delivery. One such challenge was identified as the lack of an effective carrier. Among the carriers, calcium phosphate (CaP) nanoparticles have attracted remarkable attention due to the superior biochemical properties and hold great promise for siRNA. It is well known that synthesis conditions influence the types of crystalline phases of CaPs as well as morphology. In this study, to address the influence of these parameters on the success of siRNA delivery, three different arginine (Arg) modified CaP nanoparticles having different chemical and morphological characteristics were synthesized as being the carriers of two specific siRNAs against survivin and cyclin B1. The functioning of CaP surfaces with Arg results in positive zeta potential on the surfaces. Functionalized nanoparticles have a higher loading capacity compared to unmodified particles, as they have a cationic surface that can be easily attached to negatively charged siRNAs. The gene silencing ability and the consequent in vitro antitumor activity of these CaP-Arg-siRNA complexes were investigated using A549 non-small-cell lung cancer cells. We found that high survivin and cyclin B1 expression is associated with worse survival in patients with lung cancer based on the Kaplan-Meier database. Considering the promoting role of survivin and cyclin B1 in cancer development and progression, CaP-Arg-siRNA mediated suppression of these genes resulted in a significant decrease in cell growth and induction of apoptosis. Our data suggest that all three CaP-Arg nanoparticles synthesized in this work can be used as safe and efficient nanocarriers for siRNA delivery, offering the opportunity to develop new therapeutic strategies for the treatment of lung cancer.
Transscleral Delivery of Bevacizumab-Loaded Chitosan Nanoparticles
(2019) Ugurlu, Nagihan; Asik, Mehmet Dogan; Cakmak, Hasan Basri; Tuncer, Sema; Turk, Mustafa; Cagil, Nurullah; Denkbas, Emir Baki; 30841975
Purpose: The aim of this study was to synthesize bevacizumab-loaded nanoparticles and evaluate their effects on the treatment of posterior segment diseases via subtenon injections. Methods: Bevacizumab-loaded chitosan nanoparticles (BLCNs) were synthesized by the ionic gelation method, and their physicochemical characteristics and in vitro release profile were studied. The BLCNs were characterized using atomic force microscopy (AFM), FTIR spectroscopy, dynamic light scattering, and scanning electron microscopy. The BLCNs were delivered into rabbits' eyes via posterior subtenon injections. An immunohistochemical evaluation of the ocular tissues was performed, and the vitreous humor and serum bevacizumab levels were measured by ELISA. Results: Bevacizumab-loaded chitosan nanoparticles with a diameter of 80 to 380 nm were prepared and characterized. In vitro studies showed that after the first 5 days of the experiment, a significant increase in the drug release maintained the desired drug dosage for 3 weeks. Immunohistochemical in vivo studies revealed that there were BLCNs penetrating through the sclera. Furthermore, the intravitreal bevacizumab concentration reached a maximum concentration of 18 mu g/ml, and it decreased to 6 mu g/ml after only a week. Conclusion: The results revealed that subtenon injection of BLCNs is a promising alternative to intravitreal injections. In addition to the ELISA studies, immunohistochemical experiments confirmed that BLCNs enable transscleral bevacizumab penetration, and BLCN usage may provide the required bevacizumab levels for the treatment of posterior segment diseases.