Ongun Saka | Ankara Universitesi (original) (raw)

Papers by Ongun Saka

International journal of biosensors & bioelectronics, 2018

Over the past decades, numerous biosensors have been developed for detection of various diseases.... more Over the past decades, numerous biosensors have been developed for detection of various diseases. These biosensors used specific biomarkers for their features such as sensitivity, selectivity, low cost and rapid response. This paper gives an overview of the trends in disease-related detection with affinity biosensors. Also, the advances and the challenges of using affinity biosensors are discussed.

Journal of Drug Targeting, Jun 1, 2004

While somatic gene therapy has the potential to treat many genetic disorders, recent clinical tri... more While somatic gene therapy has the potential to treat many genetic disorders, recent clinical trials suggest that an efficient and safe delivery vehicle for successful gene therapy is lacking. The current study examines the influence of two different preparation (the solvent evaporation method and the complex coacervation method) methods on the encapsulation of a model plasmid with chitosan. The ability of different molecular weights of chitosan to form nanoparticles with a plasmid, and particulated polymers to stabilize a plasmid in a supercoiled form, were examined by agarose gel electrophoresis. Protection of encapsulated pDNA offered by these nanoparticles from nuclease attack was confirmed by assessing degradation in the presence of DNase I, and the transformation of the plasmids with incubated nanoparticles were examined by beta-galactosidase assay. Model pDNA existed as a mixture of both supercoiled (84.2%) and open circular (15.8%) forms. Our results demonstrated that supercoiled forms decreased while open circular forms and fragmented linear forms increased during the preparation of formulations. F1 formulation prepared by the complex coacervation method protected the supercoiled form of pDNA effectively. There weren't any significant changes in nanoparticle size and zeta potential values at pH 5.5 for a period of 3 months, but differences in particle sizes were observed after lyophilization with a cryoprotective agent. The efficiency of nanoparticles mediated transformation to Escherichia coli cells was significantly higher than naked DNA or poly-L-lysine (PLL)-DNA polycation complexes. The transfection studies were performed in COS-7 cells. A 3-fold increase in gene expression was produced by nanoparticles as compared to the same amount of naked plasmid DNA (pDNA). These observations suggest that formulations with high molecular weight (HMW) chitosan can be an effective non-viral method of gene vector in animal studies.

International Journal of Polymeric Materials, Jul 7, 2020

Turkish journal of pharmaceutical sciences, Dec 14, 2022

Objectives: In this study, poly-(ɛ-caprolactone) (PCL) and poly-(lactic-co-glycolic acid) (PLGA) ... more Objectives: In this study, poly-(ɛ-caprolactone) (PCL) and poly-(lactic-co-glycolic acid) (PLGA) microparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. Materials and Methods: Antigen-containing microparticles were prepared using the double emulsion (w/o/w) solvent evaporation method. Results: The average geometric diameter of the particles was found to be between 7 and 24 μm, which is suitable for uptake by the antigenpresenting cells in the nasal mucosa. Although the differences were insignificant, the PLGA polymer-containing formulations exhibited the highest encapsulation efficiency. Microparticle formulations, prepared with both PLGA and PCL polymers, were successfully produced at high production yields. The in vitro release profile was presented as a biexponential process with an initial burst effect due to the release of the protein adsorbed on the microsphere surface, and the subsequent sustained release profile is the result of protein diffusion through the channels or pores formed in the polymer matrix. DT-loaded microparticles, DT solution in phosphate-buffered saline (PBS), and empty microparticles (control) were administered via nasal route and subcutaneously to guinea pigs. The antibody content of each serum sample was determined using an enzymelinked immunosorbent assay (ELISA). Conclusion: Absorbance values of the ELISA test showed that PLGA-and PCL-bearing microparticles could stimulate an adequate systemic immune response with intranasal vaccination. In addition, PLGA and PCL microparticles resulted in significantly increased IgG titers with intranasal administration as a booster dose following subcutaneous administration. PCL polymer elicited a high immune response compared with PLGA polymer (p <0.05).

Journal of Biomedical Materials Research Part B, Jan 25, 2012

An ideal gene carrier is required both in safety and efficiency for transfection. We examined the... more An ideal gene carrier is required both in safety and efficiency for transfection. We examined the use of water soluble chitosan and polyethyleneimine as a carrier for anti-angiogenic protein, TSP-1 coded, in gene delivery. The aim of this study was to synthesize and characterize polyethylene glycol conjugated cationic polymers to increase anti-angiogenic gene transfection and reduce possible cytotoxicity. Gel electrophoresis study showed strong DNA binding ability of modified cationic polymers. Also structural properties of pegylated polymers were confirmed by (1)H-NMR. We investigated in vitro properties of PEG conjugated and coated particles which were observed between 145 and 250 nm with the positive zeta potential value. In addition, the chitosan-based DNA complexes did not induce remarkable cytotoxicity against MCF-7 cells. Due to low cytotoxicity, we observed high transfection efficiency at chitosan-based formulations compared with PEI ones. Although transfection studies carried on in vitro conditions, we measured slight increases at transfection with PEGylation. PEG-conjugated chitosan formulations can be a promising candidate due to its efficiency in condensing and transfection of pDNA, its low cytotoxicty and comparatively high encapsulation degree.

Drug Delivery, Feb 24, 2014

Studies on preparation of in situ gel formulations containing diphtheria toxoid as the model acti... more Studies on preparation of in situ gel formulations containing diphtheria toxoid as the model active substance and their intranasal administration have been conducted in this study. The objective of mucosal vaccination is to stimulate both systemic and mucosal immune responses. In situ gel formulations were prepared by using, in different ratios, mixtures of Poloxamer 407 and Poloxamer 188 polymers, which gelate in a temperature-dependent manner, and mucoadhesive polymers carbopol 934, hydroxypropyl methyl cellulose, hydroxypropyl cellulose or chitosan. Following pre-formulation studies, F1, F2, F3, F4, F5, F6 and F7 formulations, which gelate at intervals and temperatures in accordance with nasal temperatures, were subjected to more comprehensive studies. For this purpose, organoleptic characteristics of the formulations were identified, their pH and mucoadhesive potencies were measured and rheological behaviors were characterized. Calculated amounts of diphtheria toxoid were added to formulations after optimization of formulations was achieved, and assay and in vitro release studies were carried out. Formulations coded F3 and F7 were considered to be superior to other formulations given the in vitro test results. Therefore, these formulations were tested in guinea pigs to determine immune responses, which they would produce following intranasal and subcutaneous administration. Absorbance values of ELISA tests and antibody neutralization test showed that formulations coded F3 and F7 were unable to stimulate adequate systemic immune response when either of the formulations was administered alone intranasally, whereas F7 resulted in significantly increased neutralizing antibody titers with intranasal administration as a booster dose following subcutaneous administration.

Drug Delivery, 2004

Chitosan can be useful as a nonviral vector for gene delivery. Although there are several reports... more Chitosan can be useful as a nonviral vector for gene delivery. Although there are several reports to form chitosan-pDNA particles, the optimization and effect on transfection remain insufficient. The chitosan-pDNA nanoparticles were formulated using complex coacervation and solvent evaporation techniques. The important parameters for the encapsulation efficiency were investigated, including molecular weight and deacetylation degree of chitosan. We found that encapsulation efficiency of pDNA is directly proportional with deacetylation degree, but there is an inverse proportion with molecular weight of chitosan. DNA-nanoparticles in the size range of 450-820 nm depend on the formulation process. The surface charge of the nanoparticles prepared with complex coacervation method was slightly positive with a zeta potential of +9 to +18 mV; nevertheless, nanoparticles prepared with solvent evaporation method had a zeta potential approximately +30 mV. The pDNA-chitosan nanoparticles prepared by using high deacetylation degree chitosan having 92.7%, 98.0%, and 90.4% encapsulation efficiency protect the encapsulated pDNA from nuclease degradation as shown by electrophoretic mobility analysis. The release of pDNA from the formulation prepared by complex coacervation was completed in 24 hr whereas the formulation prepared by evaporation technique released pDNA in 96 hr, but these release profiles are not statistically significant compared with formulations with similar structure (p &amp;amp;gt; .05). According to the results, we suggest nanoparticles have the potential to be used as a transfer vector in further studies.

Bu tez calismasinda, anjiogenezi inhibe ederek tumor buyumesini engellemepotansiyeline sahip trom... more Bu tez calismasinda, anjiogenezi inhibe ederek tumor buyumesini engellemepotansiyeline sahip trombospondin geni iceren pDNA’yi etkin, guvenilir ve dayanikliolarak hucreye tasiyabilecek nanopartikul ve lipozom formulasyonlarininhazirlanmasina yonelik calismalar gerceklestirilmistir.Bu calismamizdaki hedeflerimiz, normal damarlanma gosteren hucrelerezarar vermeden sadece anjiogenik tumor hucrelerine ozgu yanit olusturacakfarmasotik formulasyonlar gelistirmektir. Bunu saglamanin yollarindan biri,polikatyonlarin, polietilen glikol ile kimyasal modifikasyonlarinin sentezlenmesi ilekan dolasimindaki stabilitelerini artirmaktir. PEGilasyon basamagi ve etkisi in-vitroortamda incelenmistir. Ayrica, polipleks ve lipoplekslerin fizikokimyasal ozellikleri,sitotoksiteleri ve fizikofarmasotik ozellikleri arastirilmis, MCF-7 hucre hattinda genaktarim etkinlikleri incelenmistir. Formulasyon ozellikleri iyilestirilmis ve gen aktarim ozelliklerinin yuksekoldugu anlasilan L2 ve C2 kodlu formulasyonlarin, ileride in vivo calismalarda antianjiogenikyaklasim ile kanser tedavisine yonelik on bulgu elde etmek icinkullanilabilirligi sonucuna varilmistir.AbstractIn this study, novel techniques have been proposed for the development ofnanopartical and liposome formulations that will transfer a pDNA with athrombospondin gene, which has been shown to prevent tumor growth by inhibitingangiogenesis, to an active‚ safe and resistant cell.The objectives of this present work are to develop formulations that candirectly affect angiogenic tumor cells without harming cells that exhibitvasculogenesis. This can be achived by synthesizing polycations‚ which arechemically modified with polyethylene glycol‚ to improve stability in bloodcirculation. To this end‚ PEGylation step and its effects are invastigated in-vitro.Moreover‚ physicochemical properties‚ cytotoxicities and physicopharmaceuticalproperties of polyplexes and lipoplexes are examined. Furthermore‚ MCF-7 (breastcancer epithelia) cells have been used to investigate the applicability of polyplexesand lipoplexes for gene transfection efficiancy. The results of this thesis reveal that formulations‚ which are coded as L2 andC2‚ have improved formulation properties with high gene transfection properties.Accordingly‚ these formulations can be further used as a gen delivery system in thein vivo studies to obtain preliminary findings on anti-cancer treatment by antiangiogenesisapproach.

John Wiley & Sons, Inc. eBooks, Nov 12, 2007

Ankara Üniversitesi Eczacılık Fakültesi dergisi, Feb 17, 2023

Objective: Self-Emulsifying Drug Delivery System (SEDDS) has tremendous potential that has yet to... more Objective: Self-Emulsifying Drug Delivery System (SEDDS) has tremendous potential that has yet to be completely realized. They can be used in the formulation of drug compounds that have low water solubility in oral lipid administration and overcome many problems associated with these compounds. The SEDDS can increase the rate and degree of oral absorption by optimizing drug solubility in the intestinal absorption site, attributable to its small particle size, large surface area, high encapsulation efficiency, and high drug load. Furthermore, due to its lipid-based formulation, SEDDS can accelerate and increase pharmaceutical lymphatic transport, bypassing hepatic firstpass metabolism and therefore enhancing bioavailability. Result and Discussion: The quantity of novel therapeutically effective lipophilic molecules that are hydrophobic has steadily increased thanks to innovative drug development approaches. The future of pharmaceutical research may not only pass through the discovery of new molecules but also better exploitation of those already known. The use of SEDDS has been proven to be quite successful in enhancing the oral bioavailability of hydrophobic and lipophilic drug molecules among the strategies to increase the oral bioavailability of these compounds.

Die Pharmazie, 2004

Multiple water-in-oil-water (w/o/w) emulsion and polymeric nanoparticle formulations containing i... more Multiple water-in-oil-water (w/o/w) emulsion and polymeric nanoparticle formulations containing influenza virus surface antigen hemagglutinin (HA) are thought to be suitable carriers for a vaccine delivery system. The multiple emulsion technique leads to high entrapment of HA, while the solvent evaporation technique encapsulates and adsorbs HA within the nanoparticle. Immune responses of these formulations were investigated in rats and compared with the immune response raised against the conventional vaccine. The responses were detected with the hemagglutinin inhibition (HAI) assay. A single administration of multiple emulsion (F1, F2, F3) and nanoparticle (F4) formulations proved to stimulate a more effective immune response in rats than conventional vaccine.

Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2012

An ideal gene carrier is required both in safety and efficiency for transfection. We examined the... more An ideal gene carrier is required both in safety and efficiency for transfection. We examined the use of water soluble chitosan and polyethyleneimine as a carrier for anti-angiogenic protein, TSP-1 coded, in gene delivery. The aim of this study was to synthesize and characterize polyethylene glycol conjugated cationic polymers to increase anti-angiogenic gene transfection and reduce possible cytotoxicity. Gel electrophoresis study showed strong DNA binding ability of modified cationic polymers. Also structural properties of pegylated polymers were confirmed by 1 H-NMR. We investigated in vitro properties of PEG conjugated and coated particles which were observed between 145 and 250 nm with the positive zeta potential value. In addition, the chitosan-based DNA complexes did not induce remarkable cytotoxicity against MCF-7 cells. Due to low cytotoxicity, we observed high transfection efficiency at chitosan-based formulations compared with PEI ones. Although transfection studies carried on in vitro conditions, we measured slight increases at transfection with PEGylation. PEG-conjugated chitosan formulations can be a promising candidate due to its efficiency in condensing and transfection of pDNA, its low cytotoxicty and comparatively high encapsulation degree. V

International Endodontic Journal, 2008

Gö kay O, Zıraman F, Ç alı Asal A, Saka OM. Radicular peroxide penetration from carbamide peroxid... more Gö kay O, Zıraman F, Ç alı Asal A, Saka OM. Radicular peroxide penetration from carbamide peroxide gels during

Il Farmaco, 2005

This study describes an orthogonal experimental design to optimize the formulation of 5-fluoroura... more This study describes an orthogonal experimental design to optimize the formulation of 5-fluorouracil (5-FU) loaded poly D,L (lactide-coglycolide) (PLGA) nanoparticles (5FU-NP) by a nanoprecipitation-solvent displacement technique. The type of surfactant, amount of acetone and molecular weight of the polymer with three levels of each factor were selected and arranged in an L 18 (3 5) orthogonal experimental table. From the statistical analysis of the data polynominal equations were generated. Optimized formulations have the particle size ranging from 160 to 250 nm. Smallest nanoparticles (161 ± 1.22 nm) were obtained using Resomer PLGA 755 and pluronic F-68 with 10 ml acetone amount. Under these conditions the 5-FU entrapment percentage was maximum 78.30%, suggesting 5-FU might be entrapped and adsorbed on the nanoparticle surface. In vitro release of three formulations with maximum drug entrapment efficiency and minimum particle size, were also investigated by release kinetics. According to the determined coefficients, release data fit to Higuchi's diffusion kinetics. The in vitro release of 5FU-NP in phosphate buffered saline (PBS, pH 7.4) is suggested to be controlled by a combination of diffusion with slow and gradual erosion of the particles. Also, the antimicrobial activity was observed even on the end of seventh day with all formulations.

Drug Delivery, 2004

Chitosan can be useful as a nonviral vector for gene delivery. Although there are several reports... more Chitosan can be useful as a nonviral vector for gene delivery. Although there are several reports to form chitosan-pDNA particles, the optimization and effect on transfection remain insufficient. The chitosan-pDNA nanoparticles were formulated using complex coacervation and solvent evaporation techniques. The important parameters for the encapsulation efficiency were investigated, including molecular weight and deacetylation degree of chitosan. We found that encapsulation efficiency of pDNA is directly proportional with deacetylation degree, but there is an inverse proportion with molecular weight of chitosan. DNA-nanoparticles in the size range of 450-820 nm depend on the formulation process. The surface charge of the nanoparticles prepared with complex coacervation method was slightly positive with a zeta potential of +9 to +18 mV; nevertheless, nanoparticles prepared with solvent evaporation method had a zeta potential approximately +30 mV. The pDNA-chitosan nanoparticles prepared by using high deacetylation degree chitosan having 92.7%, 98.0%, and 90.4% encapsulation efficiency protect the encapsulated pDNA from nuclease degradation as shown by electrophoretic mobility analysis. The release of pDNA from the formulation prepared by complex coacervation was completed in 24 hr whereas the formulation prepared by evaporation technique released pDNA in 96 hr, but these release profiles are not statistically significant compared with formulations with similar structure (p &amp;amp;gt; .05). According to the results, we suggest nanoparticles have the potential to be used as a transfer vector in further studies.

Pharmaceutica Analytica Acta, 2011

Journal of pharmaceutical sciences, 2021

In recent years, biomaterial-based treatments, also called guided bone regeneration (GBR), which ... more In recent years, biomaterial-based treatments, also called guided bone regeneration (GBR), which aim to establish a bone regeneration site and prevent the migration of gingival connective tissue and / or peripheral epithelium through the defective area during periodontal surgical procedures have come to the fore. In this report, we have developed a nanoparticle bearing thermosensitive in situ gel formulation of Pluronic F127 and poly(D,L-lactic acid) based membrane to reveal their utilization at GBR by in-vivo applications. In addition, the encouragement of the bone formation in defect area via inhibition of osteoclastic activity is intended by fabrication these biodegradable biomaterials at a lowered Zoledronic Acid (ZA) dose. Both of the developed materials remained stable under specified stability conditions (25°C, 6 months) and provided the extended release profile of ZA. The in-vivo efficacy of nanoparticle bearing in situ gel formulation, membrane formulation and simultaneous ...

Akdeniz Medical Journal

Amaç: Gündelik insan yaşamındaki küçük yaralanmalarda hijyeni sağlama amacıyla antiseptik olarak ... more Amaç: Gündelik insan yaşamındaki küçük yaralanmalarda hijyeni sağlama amacıyla antiseptik olarak reçetelendirilen tentürdiyot ürününün, kaç eczanede hazırlatılabildiğini ve ne kadar doğru hazırlandığını/sunulduğunu saptamak amaçlanmıştır. Sayısı fazla olmasa da, haricen kullanılan bazı ilaçlar majistral olarak reçetelenmekte ve reçeteye uygun şekilde eczanelerde hazırlanarak, hastaların kullanımına sunulmaktadır. Ülkemizde olduğu gibi diğer ülkelerde de; gerek hastane gerekse eczane eczacılığında majistral ilaçların hâlâ önemini koruduğu bilinmektedir. Gereç ve Yöntemler: Ankara ve çevresinde kayıtlı olan eczanelerde çalışma gerçekleştirilmiştir. Rastgele seçilen eczanelerden temin edilen iyot-tentürlerinin hastaya sunum özellikleri, etiket ve ambalaj malzemesi seçimleri incelenmiştir. Majistral ilaçların içerdiği iyot ve sodyum iyodür miktarları farmakopede belirtilen titrasyon metodu ile tayin edilmiş ve farmakopede belirtilen aralık içerisinde olup olmadığı kontrol edilmiştir. Bulgular: Rastgele seçilen eczanelerden sadece %32'sinde ilaç ürettirilirken, ticari preperat ile yapılan içerik karşılaştırması ve farmakope standartlarına uyum gösteren ürün oranı %87,5 olarak saptanmıştır. Ambalaj ve kapak malzemesi ile etiket çeşidinin seçiminde tüm eczaneler doğru tercih yapmışlardır. Lakin etiket bilgileri kontrol edildiğinde bazı eksikliklere rastlanmıştır. Ticari preperatlar kontrol edildiğinde ise iyot ve sodyum iyodür içerikleri farmakopelerde izin verilen aralık içerisinde olduğu saptanmıştır. Sonuç: İlaç sanayisi tarafından hazırlanan ofisinal ilaçların kontrolleri üretim sırasında ve piyasaya verilmeden önce üretici firma tarafından yapılmaktadır. Ayrıca ülkelerdeki ilgili sağlık otoritesi ise gerekli gördüğünde piyasadaki ilaçlar üzerinde kontrol ve incelemelerini gerçekleştirmektedir. Majistral ilaçlarda kullanılan maddelerin temin yerleri ile hazırlanmış ürünlerin içeriklerinin kontrol edildiği herhangi bir mekanizma yoktur. Majistral ilaca ulaştıktan sonra, ilacın yetersiz içeriği ve/veya yanlış bilgilendirme durumunda, kişinin doğru tedavi alabilmesi için ilaçların hazırlanması ve etkin/ yardımcı madde temin basamaklarının da düzenli olarak denetlenmesine ihtiyaç duyulduğu tespit edilmiştir.

International journal of biosensors & bioelectronics, 2018

Over the past decades, numerous biosensors have been developed for detection of various diseases.... more Over the past decades, numerous biosensors have been developed for detection of various diseases. These biosensors used specific biomarkers for their features such as sensitivity, selectivity, low cost and rapid response. This paper gives an overview of the trends in disease-related detection with affinity biosensors. Also, the advances and the challenges of using affinity biosensors are discussed.

Journal of Drug Targeting, Jun 1, 2004

While somatic gene therapy has the potential to treat many genetic disorders, recent clinical tri... more While somatic gene therapy has the potential to treat many genetic disorders, recent clinical trials suggest that an efficient and safe delivery vehicle for successful gene therapy is lacking. The current study examines the influence of two different preparation (the solvent evaporation method and the complex coacervation method) methods on the encapsulation of a model plasmid with chitosan. The ability of different molecular weights of chitosan to form nanoparticles with a plasmid, and particulated polymers to stabilize a plasmid in a supercoiled form, were examined by agarose gel electrophoresis. Protection of encapsulated pDNA offered by these nanoparticles from nuclease attack was confirmed by assessing degradation in the presence of DNase I, and the transformation of the plasmids with incubated nanoparticles were examined by beta-galactosidase assay. Model pDNA existed as a mixture of both supercoiled (84.2%) and open circular (15.8%) forms. Our results demonstrated that supercoiled forms decreased while open circular forms and fragmented linear forms increased during the preparation of formulations. F1 formulation prepared by the complex coacervation method protected the supercoiled form of pDNA effectively. There weren&amp;amp;#39;t any significant changes in nanoparticle size and zeta potential values at pH 5.5 for a period of 3 months, but differences in particle sizes were observed after lyophilization with a cryoprotective agent. The efficiency of nanoparticles mediated transformation to Escherichia coli cells was significantly higher than naked DNA or poly-L-lysine (PLL)-DNA polycation complexes. The transfection studies were performed in COS-7 cells. A 3-fold increase in gene expression was produced by nanoparticles as compared to the same amount of naked plasmid DNA (pDNA). These observations suggest that formulations with high molecular weight (HMW) chitosan can be an effective non-viral method of gene vector in animal studies.

International Journal of Polymeric Materials, Jul 7, 2020

Turkish journal of pharmaceutical sciences, Dec 14, 2022

Objectives: In this study, poly-(ɛ-caprolactone) (PCL) and poly-(lactic-co-glycolic acid) (PLGA) ... more Objectives: In this study, poly-(ɛ-caprolactone) (PCL) and poly-(lactic-co-glycolic acid) (PLGA) microparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. Materials and Methods: Antigen-containing microparticles were prepared using the double emulsion (w/o/w) solvent evaporation method. Results: The average geometric diameter of the particles was found to be between 7 and 24 μm, which is suitable for uptake by the antigenpresenting cells in the nasal mucosa. Although the differences were insignificant, the PLGA polymer-containing formulations exhibited the highest encapsulation efficiency. Microparticle formulations, prepared with both PLGA and PCL polymers, were successfully produced at high production yields. The in vitro release profile was presented as a biexponential process with an initial burst effect due to the release of the protein adsorbed on the microsphere surface, and the subsequent sustained release profile is the result of protein diffusion through the channels or pores formed in the polymer matrix. DT-loaded microparticles, DT solution in phosphate-buffered saline (PBS), and empty microparticles (control) were administered via nasal route and subcutaneously to guinea pigs. The antibody content of each serum sample was determined using an enzymelinked immunosorbent assay (ELISA). Conclusion: Absorbance values of the ELISA test showed that PLGA-and PCL-bearing microparticles could stimulate an adequate systemic immune response with intranasal vaccination. In addition, PLGA and PCL microparticles resulted in significantly increased IgG titers with intranasal administration as a booster dose following subcutaneous administration. PCL polymer elicited a high immune response compared with PLGA polymer (p <0.05).

Journal of Biomedical Materials Research Part B, Jan 25, 2012

An ideal gene carrier is required both in safety and efficiency for transfection. We examined the... more An ideal gene carrier is required both in safety and efficiency for transfection. We examined the use of water soluble chitosan and polyethyleneimine as a carrier for anti-angiogenic protein, TSP-1 coded, in gene delivery. The aim of this study was to synthesize and characterize polyethylene glycol conjugated cationic polymers to increase anti-angiogenic gene transfection and reduce possible cytotoxicity. Gel electrophoresis study showed strong DNA binding ability of modified cationic polymers. Also structural properties of pegylated polymers were confirmed by (1)H-NMR. We investigated in vitro properties of PEG conjugated and coated particles which were observed between 145 and 250 nm with the positive zeta potential value. In addition, the chitosan-based DNA complexes did not induce remarkable cytotoxicity against MCF-7 cells. Due to low cytotoxicity, we observed high transfection efficiency at chitosan-based formulations compared with PEI ones. Although transfection studies carried on in vitro conditions, we measured slight increases at transfection with PEGylation. PEG-conjugated chitosan formulations can be a promising candidate due to its efficiency in condensing and transfection of pDNA, its low cytotoxicty and comparatively high encapsulation degree.

Drug Delivery, Feb 24, 2014

Studies on preparation of in situ gel formulations containing diphtheria toxoid as the model acti... more Studies on preparation of in situ gel formulations containing diphtheria toxoid as the model active substance and their intranasal administration have been conducted in this study. The objective of mucosal vaccination is to stimulate both systemic and mucosal immune responses. In situ gel formulations were prepared by using, in different ratios, mixtures of Poloxamer 407 and Poloxamer 188 polymers, which gelate in a temperature-dependent manner, and mucoadhesive polymers carbopol 934, hydroxypropyl methyl cellulose, hydroxypropyl cellulose or chitosan. Following pre-formulation studies, F1, F2, F3, F4, F5, F6 and F7 formulations, which gelate at intervals and temperatures in accordance with nasal temperatures, were subjected to more comprehensive studies. For this purpose, organoleptic characteristics of the formulations were identified, their pH and mucoadhesive potencies were measured and rheological behaviors were characterized. Calculated amounts of diphtheria toxoid were added to formulations after optimization of formulations was achieved, and assay and in vitro release studies were carried out. Formulations coded F3 and F7 were considered to be superior to other formulations given the in vitro test results. Therefore, these formulations were tested in guinea pigs to determine immune responses, which they would produce following intranasal and subcutaneous administration. Absorbance values of ELISA tests and antibody neutralization test showed that formulations coded F3 and F7 were unable to stimulate adequate systemic immune response when either of the formulations was administered alone intranasally, whereas F7 resulted in significantly increased neutralizing antibody titers with intranasal administration as a booster dose following subcutaneous administration.

Drug Delivery, 2004

Chitosan can be useful as a nonviral vector for gene delivery. Although there are several reports... more Chitosan can be useful as a nonviral vector for gene delivery. Although there are several reports to form chitosan-pDNA particles, the optimization and effect on transfection remain insufficient. The chitosan-pDNA nanoparticles were formulated using complex coacervation and solvent evaporation techniques. The important parameters for the encapsulation efficiency were investigated, including molecular weight and deacetylation degree of chitosan. We found that encapsulation efficiency of pDNA is directly proportional with deacetylation degree, but there is an inverse proportion with molecular weight of chitosan. DNA-nanoparticles in the size range of 450-820 nm depend on the formulation process. The surface charge of the nanoparticles prepared with complex coacervation method was slightly positive with a zeta potential of +9 to +18 mV; nevertheless, nanoparticles prepared with solvent evaporation method had a zeta potential approximately +30 mV. The pDNA-chitosan nanoparticles prepared by using high deacetylation degree chitosan having 92.7%, 98.0%, and 90.4% encapsulation efficiency protect the encapsulated pDNA from nuclease degradation as shown by electrophoretic mobility analysis. The release of pDNA from the formulation prepared by complex coacervation was completed in 24 hr whereas the formulation prepared by evaporation technique released pDNA in 96 hr, but these release profiles are not statistically significant compared with formulations with similar structure (p &amp;amp;gt; .05). According to the results, we suggest nanoparticles have the potential to be used as a transfer vector in further studies.

Bu tez calismasinda, anjiogenezi inhibe ederek tumor buyumesini engellemepotansiyeline sahip trom... more Bu tez calismasinda, anjiogenezi inhibe ederek tumor buyumesini engellemepotansiyeline sahip trombospondin geni iceren pDNA’yi etkin, guvenilir ve dayanikliolarak hucreye tasiyabilecek nanopartikul ve lipozom formulasyonlarininhazirlanmasina yonelik calismalar gerceklestirilmistir.Bu calismamizdaki hedeflerimiz, normal damarlanma gosteren hucrelerezarar vermeden sadece anjiogenik tumor hucrelerine ozgu yanit olusturacakfarmasotik formulasyonlar gelistirmektir. Bunu saglamanin yollarindan biri,polikatyonlarin, polietilen glikol ile kimyasal modifikasyonlarinin sentezlenmesi ilekan dolasimindaki stabilitelerini artirmaktir. PEGilasyon basamagi ve etkisi in-vitroortamda incelenmistir. Ayrica, polipleks ve lipoplekslerin fizikokimyasal ozellikleri,sitotoksiteleri ve fizikofarmasotik ozellikleri arastirilmis, MCF-7 hucre hattinda genaktarim etkinlikleri incelenmistir. Formulasyon ozellikleri iyilestirilmis ve gen aktarim ozelliklerinin yuksekoldugu anlasilan L2 ve C2 kodlu formulasyonlarin, ileride in vivo calismalarda antianjiogenikyaklasim ile kanser tedavisine yonelik on bulgu elde etmek icinkullanilabilirligi sonucuna varilmistir.AbstractIn this study, novel techniques have been proposed for the development ofnanopartical and liposome formulations that will transfer a pDNA with athrombospondin gene, which has been shown to prevent tumor growth by inhibitingangiogenesis, to an active‚ safe and resistant cell.The objectives of this present work are to develop formulations that candirectly affect angiogenic tumor cells without harming cells that exhibitvasculogenesis. This can be achived by synthesizing polycations‚ which arechemically modified with polyethylene glycol‚ to improve stability in bloodcirculation. To this end‚ PEGylation step and its effects are invastigated in-vitro.Moreover‚ physicochemical properties‚ cytotoxicities and physicopharmaceuticalproperties of polyplexes and lipoplexes are examined. Furthermore‚ MCF-7 (breastcancer epithelia) cells have been used to investigate the applicability of polyplexesand lipoplexes for gene transfection efficiancy. The results of this thesis reveal that formulations‚ which are coded as L2 andC2‚ have improved formulation properties with high gene transfection properties.Accordingly‚ these formulations can be further used as a gen delivery system in thein vivo studies to obtain preliminary findings on anti-cancer treatment by antiangiogenesisapproach.

John Wiley & Sons, Inc. eBooks, Nov 12, 2007

Ankara Üniversitesi Eczacılık Fakültesi dergisi, Feb 17, 2023

Objective: Self-Emulsifying Drug Delivery System (SEDDS) has tremendous potential that has yet to... more Objective: Self-Emulsifying Drug Delivery System (SEDDS) has tremendous potential that has yet to be completely realized. They can be used in the formulation of drug compounds that have low water solubility in oral lipid administration and overcome many problems associated with these compounds. The SEDDS can increase the rate and degree of oral absorption by optimizing drug solubility in the intestinal absorption site, attributable to its small particle size, large surface area, high encapsulation efficiency, and high drug load. Furthermore, due to its lipid-based formulation, SEDDS can accelerate and increase pharmaceutical lymphatic transport, bypassing hepatic firstpass metabolism and therefore enhancing bioavailability. Result and Discussion: The quantity of novel therapeutically effective lipophilic molecules that are hydrophobic has steadily increased thanks to innovative drug development approaches. The future of pharmaceutical research may not only pass through the discovery of new molecules but also better exploitation of those already known. The use of SEDDS has been proven to be quite successful in enhancing the oral bioavailability of hydrophobic and lipophilic drug molecules among the strategies to increase the oral bioavailability of these compounds.

Die Pharmazie, 2004

Multiple water-in-oil-water (w/o/w) emulsion and polymeric nanoparticle formulations containing i... more Multiple water-in-oil-water (w/o/w) emulsion and polymeric nanoparticle formulations containing influenza virus surface antigen hemagglutinin (HA) are thought to be suitable carriers for a vaccine delivery system. The multiple emulsion technique leads to high entrapment of HA, while the solvent evaporation technique encapsulates and adsorbs HA within the nanoparticle. Immune responses of these formulations were investigated in rats and compared with the immune response raised against the conventional vaccine. The responses were detected with the hemagglutinin inhibition (HAI) assay. A single administration of multiple emulsion (F1, F2, F3) and nanoparticle (F4) formulations proved to stimulate a more effective immune response in rats than conventional vaccine.

Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2012

An ideal gene carrier is required both in safety and efficiency for transfection. We examined the... more An ideal gene carrier is required both in safety and efficiency for transfection. We examined the use of water soluble chitosan and polyethyleneimine as a carrier for anti-angiogenic protein, TSP-1 coded, in gene delivery. The aim of this study was to synthesize and characterize polyethylene glycol conjugated cationic polymers to increase anti-angiogenic gene transfection and reduce possible cytotoxicity. Gel electrophoresis study showed strong DNA binding ability of modified cationic polymers. Also structural properties of pegylated polymers were confirmed by 1 H-NMR. We investigated in vitro properties of PEG conjugated and coated particles which were observed between 145 and 250 nm with the positive zeta potential value. In addition, the chitosan-based DNA complexes did not induce remarkable cytotoxicity against MCF-7 cells. Due to low cytotoxicity, we observed high transfection efficiency at chitosan-based formulations compared with PEI ones. Although transfection studies carried on in vitro conditions, we measured slight increases at transfection with PEGylation. PEG-conjugated chitosan formulations can be a promising candidate due to its efficiency in condensing and transfection of pDNA, its low cytotoxicty and comparatively high encapsulation degree. V

International Endodontic Journal, 2008

Gö kay O, Zıraman F, Ç alı Asal A, Saka OM. Radicular peroxide penetration from carbamide peroxid... more Gö kay O, Zıraman F, Ç alı Asal A, Saka OM. Radicular peroxide penetration from carbamide peroxide gels during

Il Farmaco, 2005

This study describes an orthogonal experimental design to optimize the formulation of 5-fluoroura... more This study describes an orthogonal experimental design to optimize the formulation of 5-fluorouracil (5-FU) loaded poly D,L (lactide-coglycolide) (PLGA) nanoparticles (5FU-NP) by a nanoprecipitation-solvent displacement technique. The type of surfactant, amount of acetone and molecular weight of the polymer with three levels of each factor were selected and arranged in an L 18 (3 5) orthogonal experimental table. From the statistical analysis of the data polynominal equations were generated. Optimized formulations have the particle size ranging from 160 to 250 nm. Smallest nanoparticles (161 ± 1.22 nm) were obtained using Resomer PLGA 755 and pluronic F-68 with 10 ml acetone amount. Under these conditions the 5-FU entrapment percentage was maximum 78.30%, suggesting 5-FU might be entrapped and adsorbed on the nanoparticle surface. In vitro release of three formulations with maximum drug entrapment efficiency and minimum particle size, were also investigated by release kinetics. According to the determined coefficients, release data fit to Higuchi's diffusion kinetics. The in vitro release of 5FU-NP in phosphate buffered saline (PBS, pH 7.4) is suggested to be controlled by a combination of diffusion with slow and gradual erosion of the particles. Also, the antimicrobial activity was observed even on the end of seventh day with all formulations.

Drug Delivery, 2004

Chitosan can be useful as a nonviral vector for gene delivery. Although there are several reports... more Chitosan can be useful as a nonviral vector for gene delivery. Although there are several reports to form chitosan-pDNA particles, the optimization and effect on transfection remain insufficient. The chitosan-pDNA nanoparticles were formulated using complex coacervation and solvent evaporation techniques. The important parameters for the encapsulation efficiency were investigated, including molecular weight and deacetylation degree of chitosan. We found that encapsulation efficiency of pDNA is directly proportional with deacetylation degree, but there is an inverse proportion with molecular weight of chitosan. DNA-nanoparticles in the size range of 450-820 nm depend on the formulation process. The surface charge of the nanoparticles prepared with complex coacervation method was slightly positive with a zeta potential of +9 to +18 mV; nevertheless, nanoparticles prepared with solvent evaporation method had a zeta potential approximately +30 mV. The pDNA-chitosan nanoparticles prepared by using high deacetylation degree chitosan having 92.7%, 98.0%, and 90.4% encapsulation efficiency protect the encapsulated pDNA from nuclease degradation as shown by electrophoretic mobility analysis. The release of pDNA from the formulation prepared by complex coacervation was completed in 24 hr whereas the formulation prepared by evaporation technique released pDNA in 96 hr, but these release profiles are not statistically significant compared with formulations with similar structure (p &amp;amp;gt; .05). According to the results, we suggest nanoparticles have the potential to be used as a transfer vector in further studies.

Pharmaceutica Analytica Acta, 2011

Journal of pharmaceutical sciences, 2021

In recent years, biomaterial-based treatments, also called guided bone regeneration (GBR), which ... more In recent years, biomaterial-based treatments, also called guided bone regeneration (GBR), which aim to establish a bone regeneration site and prevent the migration of gingival connective tissue and / or peripheral epithelium through the defective area during periodontal surgical procedures have come to the fore. In this report, we have developed a nanoparticle bearing thermosensitive in situ gel formulation of Pluronic F127 and poly(D,L-lactic acid) based membrane to reveal their utilization at GBR by in-vivo applications. In addition, the encouragement of the bone formation in defect area via inhibition of osteoclastic activity is intended by fabrication these biodegradable biomaterials at a lowered Zoledronic Acid (ZA) dose. Both of the developed materials remained stable under specified stability conditions (25°C, 6 months) and provided the extended release profile of ZA. The in-vivo efficacy of nanoparticle bearing in situ gel formulation, membrane formulation and simultaneous ...

Akdeniz Medical Journal

Amaç: Gündelik insan yaşamındaki küçük yaralanmalarda hijyeni sağlama amacıyla antiseptik olarak ... more Amaç: Gündelik insan yaşamındaki küçük yaralanmalarda hijyeni sağlama amacıyla antiseptik olarak reçetelendirilen tentürdiyot ürününün, kaç eczanede hazırlatılabildiğini ve ne kadar doğru hazırlandığını/sunulduğunu saptamak amaçlanmıştır. Sayısı fazla olmasa da, haricen kullanılan bazı ilaçlar majistral olarak reçetelenmekte ve reçeteye uygun şekilde eczanelerde hazırlanarak, hastaların kullanımına sunulmaktadır. Ülkemizde olduğu gibi diğer ülkelerde de; gerek hastane gerekse eczane eczacılığında majistral ilaçların hâlâ önemini koruduğu bilinmektedir. Gereç ve Yöntemler: Ankara ve çevresinde kayıtlı olan eczanelerde çalışma gerçekleştirilmiştir. Rastgele seçilen eczanelerden temin edilen iyot-tentürlerinin hastaya sunum özellikleri, etiket ve ambalaj malzemesi seçimleri incelenmiştir. Majistral ilaçların içerdiği iyot ve sodyum iyodür miktarları farmakopede belirtilen titrasyon metodu ile tayin edilmiş ve farmakopede belirtilen aralık içerisinde olup olmadığı kontrol edilmiştir. Bulgular: Rastgele seçilen eczanelerden sadece %32'sinde ilaç ürettirilirken, ticari preperat ile yapılan içerik karşılaştırması ve farmakope standartlarına uyum gösteren ürün oranı %87,5 olarak saptanmıştır. Ambalaj ve kapak malzemesi ile etiket çeşidinin seçiminde tüm eczaneler doğru tercih yapmışlardır. Lakin etiket bilgileri kontrol edildiğinde bazı eksikliklere rastlanmıştır. Ticari preperatlar kontrol edildiğinde ise iyot ve sodyum iyodür içerikleri farmakopelerde izin verilen aralık içerisinde olduğu saptanmıştır. Sonuç: İlaç sanayisi tarafından hazırlanan ofisinal ilaçların kontrolleri üretim sırasında ve piyasaya verilmeden önce üretici firma tarafından yapılmaktadır. Ayrıca ülkelerdeki ilgili sağlık otoritesi ise gerekli gördüğünde piyasadaki ilaçlar üzerinde kontrol ve incelemelerini gerçekleştirmektedir. Majistral ilaçlarda kullanılan maddelerin temin yerleri ile hazırlanmış ürünlerin içeriklerinin kontrol edildiği herhangi bir mekanizma yoktur. Majistral ilaca ulaştıktan sonra, ilacın yetersiz içeriği ve/veya yanlış bilgilendirme durumunda, kişinin doğru tedavi alabilmesi için ilaçların hazırlanması ve etkin/ yardımcı madde temin basamaklarının da düzenli olarak denetlenmesine ihtiyaç duyulduğu tespit edilmiştir.