Person: KERİMOĞLU, OYA
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KERİMOĞLU
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Publication Metadata only Release behaviour and biocompatibility of drug-loaded pH sensitive particles(ELSEVIER, 2006) KERİMOĞLU, OYA; Sipahigil, O; Gursoy, A; Cakalagaoglu, F; Okar, ITThe purpose of this work was to investigate the physical properties of drug-loaded poly(methacrylic acid-g-ethylene glycol) {P(MAA-g-EG)} particles, their biocompatibility with the gastrointestinal tract of rats and also the effects of these particles on the tight junctions of the rat intestinal epithelium. Model drugs such as diltiazem HCl, diclofenac Na, ciprofloxacin HCl and isoniazid were used in this study. P(MAA-g-EG) particles were prepared by free radical solution polymerization of methacrylic acid (MAA) and poly(ethylene glycol) (PEG). The loading efficiency of the model drugs in the particles and in vitro release profiles were investigated in pH 7.4 phosphate buffer and in gradually pH changing buffers (pH 1.2, 5.8, 6.8 and 7.4). The stability of free particles and drug-loaded particles was established by Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). In conclusion, P(MAA-g-EG) particles controlled the release rate of small molecular weight model drugs according to the pH of the medium. Stability of those particles loaded with drugs did not change in accelerated stability conditions. Histopathological results indicated that loading drugs to the particles prevented cell and tissue damage after 20 h. Free particles showed no change of tight junctions after 2 and 10 h. The results of TEM showed that increasing the amount of P(MAA-g-EG) particles from 100 to 385 mg clearly opened the tight junction, but with serious epithelial cell disruption. (c) 2005 Elsevier B.V. All rights reserved.Publication Open Access Formulation and evaluation of vascular endothelial growth factor loaded polycaprolactone nanoparticles(2022-01-01) KERİMOĞLU, OYA; ÖZER ÖNDER, SETENAY; ALARÇİN, EMİNE; KARSLI, SEHER; KERİMOĞLU O., Ozer-Onder S., ALARÇİN E., KARSLI S.In an attempt to increase molecular stability and provide controlled release, vascular endothelial growth factor (VEGF) was encapsulated into polycaprolactone (PCL) nanoparticles. Both VEGF-free and VEGF-loaded PCL nanoparticles were formulated by w/o/w double emulsion of the dichloromethane-water system in the presence of polyvinyl alcohol ( PVA) and rat serum albumin. To achieve the optimal formulation concerning particle size and monodispersity, studies were carried out with different formulation parameters, including PVA concentration, homogenization time and rate. Scanning electron microscopy and dynamic light scattering analysis showed respectively that particles had a spherical shape with a smooth surface and particle size varying between 58.68-751.9 nm. All of the formulations were negatively charged according to zeta potential analysis. In vitro release study was performed in pH 7.4 phosphate-buffered saline at 37 degrees C and released VEGF amount was measured by enzyme-linked immunosorbent assay (ELISA) method. At the end of the 35th day, 10% of total encapsulated VEGF was released with a sustained-release profile, which fitted the Korsmeyer-Peppas kinetic model. The bioactivation of the nanoparticles was evaluated using XTT and ELISA methods. As a result, the released VEGF was biologically active and also VEGF loaded PCL nanoparticles enhanced proliferation of the human umbilical vein endothelial cells in cell culture.Publication Metadata only Nanocarriers: Novel Approaches to Oral Delivery of Insulin(MARMARA UNIV, INST HEALTH SCIENCES, 2017) KERİMOĞLU, OYA; Ozer, Setenay; Kerimoglu, Oya; Ugurlu, TimucinDiabetes is among the major chronic diseases at present, and no medication has been developed that can replace the roles of endogenous insulin, especially for type 1 diabetes patients. However, insulin can be frequently administered by the subcutaneous route as a protein macromolecule because enzymatic and absorption-associated problems. It leads to immunogenic symptoms, adipose tissue complaints such as lipodystrophy, and hyperinsulinemia risks because of pharmacokinetic properties that do exactly overlap with those of endogenous insulin. In a remarkable number of patients, failure to attain permanent glycemic control by subcutaneous insulin treatment has shown by clinical trials based on noncompliance. Oral drug administration has always been the most preferred administration pathway for drugs with high patient compliance and convenience. Difficulties in the use of subcutaneous insulin have prompted scientists to find solutions for the oral administration of insulin. Similar to many other fields, nanotechnology has recently come to the fore in the pharmaceutical field. Compared with conventional systems, nanopharmaceuticals are drug delivery systems that enable promoted absorption, protection of the active ingredient from the external environment, lower dose applications, higher bioavailability, controlled release, and prolonged residence time. In vitro and in vivo studies have been performed with varied nanopharmaceutical systems in order to administer insulin orally for this purpose.Publication Open Access Novel Use of Pectin as a Microneedle Base(PHARMACEUTICAL SOC JAPAN, 2015) KERİMOĞLU, OYA; Demir, Yusuf Kemal; Kerimoglu, OyaHydrocolloid pectin formulation was utilized as a novel base for fabricating biodegradable micro-needle (MN) arrays. The pectin MNs were, on average, found to be 897.71 +/- 3.48 mu m in height and 234.31 +/- 2.27 mu m in base width, with an inter base spacing of 498.66 +/- 1.60 mu m, and corresponding to an aspect ratio of 3.83 +/- 0.04. Bovine serum albumin (BSA) and pectin gel interaction was found to be dependent on the loaded protein amount. By contrast, regardless of the amount of BSA incorporated, pectin MNs competed with BSA to form a complex with Cu2+ ions in a bicinchoninic acid (BCA) kit. The glass transition of the pectin MN base was found to be 145.15 +/- 12.09, with a delta Cp of 2.60 +/- 0.02Jg(-1)K(-1). Because pectin MNs are skin friendly and naturally occurring, with biodegradable and hydrocolloidal features, they are promising vehicle for the controlled release of macromolecules.Publication Metadata only Multilayered Tablet Technology, Manufacturing Process, Evaluation and its Application Areas(MARMARA UNIV, FAC MEDICINE, 2016) KERİMOĞLU, OYA; Canbagi, Hatice; Ugurlu, Timucin; Kerimoglu, OyaAccording to new developed technologies, drug industry is also trying to refresh and improve itself. With the conception of rational pharmacotherapy, new technologies becomes smarter than finding new active substances. Correspondingly as a new dosage system, multi-layer tablets that improved to serve this purpose, provides ease of use to patients, reduces the side effects and increases of effectiveness of active agent. Therefore multi-layer tablets are developed to improve both the quality of product and life. Conducted work studied for understanding the bi-layer tablet technique, evaluating the assesment parameters and to giving examples to used spaces.Publication Metadata only Coprecipitation of Cefuroxime Axetil-PVP composite microparticles by batch supercritical antisolvent process(ELSEVIER SCIENCE BV, 2011) KERİMOĞLU, OYA; Uzun, Ipar Nimet; Sipahigil, Oya; Dincer, SalihBatch supercritical antisolvent precipitation (SAS) process was used to coprecipitate Cefuroxime Axetil amorphous (CFA, antibiotic) and Polyvinylpyrrolidone (PVP-K30) for preparing drug-polymer composite particles. Solutions of CFA and PVP-K30 in methanol with overall concentrations of 50-150 mg/ml and polymer/drug ratios of 1/1-4/1 were sprayed into the CO2 at 70-200 bar and 35-50 degrees C with drug + polymer solution injection rates of 0.85 and 2.5 ml/min. Spherical particles having mean diameters of 1.88-3.97 mu m, distribution ranges of 0.82-9.7 mu m (the narrowest distribution) and 0.91-46.64 mu m (the broadest distribution) were obtained. Mean particle size was not affected significantly with the change of process parameters. It was only affected by pressure change. On the other hand particle size distribution was affected by pressure, temperature, drug + polymer solution injection rate and concentration. It was observed that temperature and polymer/drug ratio affected the particle morphology most. The drug release rate of SAS-coprecipitated CFA-PVP (1/1) particles was almost 10 times slower than the drug alone. As the ratio of the polymer increased drug release rate also increased due to the wetting effect of PVP. Crown Copyright (C) 2010 Published by Elsevier B.V. All rights reserved.Publication Open Access Sodium Alginate Microneedle Arrays Mediate the Transdermal Delivery of Bovine Serum Albumin(PUBLIC LIBRARY SCIENCE, 2013-05-10) KERİMOĞLU, OYA; Demir, Yusuf K.; Akan, Zafer; Kerimoglu, OyaBackground: The poke and release strategy for the delivery of macromolecules using polymeric microneedle (MN) is of great importance because it eliminates microneedle reuse, the risks of biohazardous sharps and cross contamination, and it requires no special disposal mechanism. The main objective of this study was the determination of the stability and delivery of bovine serum albumin (BSA) that was transported across human skin via sodium alginate (SA) microneedle arrays (MNs) and SA needle free patches using two different analytical methods. Methodology and Findings: The capability of two analytical methods, the bicinchoninic acid (BCA) assay and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), to precisely detect and quantify BSA within different types of polymeric MNs was assessed. The ex vivo protein release of BSA across dermatomed human abdominal skin from 10 w/w SA MNs was compared to that from needle-free patches using Franz diffusion cells. The developed applicator was mechanically characterized using a Texture Analyzer. The patch mold and its components were fabricated using a rapid prototyping machine. Conclusions/Significance: The BCA method was able to precisely detect BSA that had been loaded into SA MNs. However, the use of SDS-PAGE as the analytical method resulted in significantly different amounts of BSA recovered from differently conditioned polymeric MNs. The permeation of BSA across dermatomed human abdominal skin by SA MNs, which were composed of 100 pyramidal needles, increased by approximately 15.4 fold compared to the permeation obtained with SA needle-free patches. The ease of use of the applicator during the release studies was also demonstrated, as was its mechanical characterization.Publication Open Access Characterization of Polymeric Microneedle Arrays for Transdermal Drug Delivery(PUBLIC LIBRARY SCIENCE, 2013-10-23) KERİMOĞLU, OYA; Demir, Yusuf K.; Akan, Zafer; Kerimoglu, OyaMicrofabrication of dissolvable, swellable, and biodegradable polymeric microneedle arrays (MNs) were extensively investigated based in a nano sensitive fabrication style known as micromilling that is then combined with conventional micromolding technique. The aim of this study was to describe the polymer selection, and optimize formulation compounding parameters for various polymeric MNs. Inverse replication of micromilled master MNs reproduced with polydimethylsiloxane (PDMS), where solid out of plane polymeric MNs were subsequently assembled, and physicochemically characterized. Dissolvable, swellable, and biodegradable MNs were constructed to depth of less than 1 mm with an aspect ratio of 3.6, and 1/2 mm of both inter needle tip and base spacing. Micromolding step also enabled to replicate the MNs very precisely and accurate. Polymeric microneedles (MN) precision was ranging from +/- 0.18 to +/- 1.82% for microneedle height, +/- 0.45 to +/- 1.42% for base diameter, and +/- 0.22 to +/- 0.95% for interbase spacing. Although dissolvable sodium alginate MN showed less physical robustness than biodegradable polylactic-co-glycolic acid MN, their thermogravimetric analysis is of promise for constructing these polymeric types of matrix devices.Publication Metadata only Preparation and in vitro evaluation of verapamil HCl and ibuprofen containing carrageenan beads(2001) KERİMOĞLU, OYA; Sipahigil, O.; Dortunç, B.The objective of this study was to prepare and evaluate carrageenan beads as a controlled release system for a freely water soluble drug verapamil hydrochloride and a slightly water soluble drug ibuprofen. Beads were prepared by ionotropic gelation method. The influence of formulation factors (drug content, polymer concentration, counterion type and concentration, outer phase volume) on the particle size, encapsulation efficiency and in vitro release characteristics of beads was investigated. The encapsulation efficiency of veraparnil HCl in the beads (34.8-71.1%) was higher than that of ibuprofen (23.6-58%). While about 30% of ibuprofen was released at 6 h, about 70% of verapamil HCl was released in 5 h from the carrageenan beads prepared.Publication Metadata only Vascular endothelial growth factor-loaded poly(lactic-co-glycolic acid) microspheres-induced lateral axonal sprouting into the vein graft bridging two healthy nerves: Nerve graft prefabrication using controlled release system(WILEY-BLACKWELL, 2012) AKAKIN, DİLEK; Karagoz, Huseyin; Ulkur, Ersin; Kerimoglu, Oya; Alarcin, Emine; Sahin, Cihan; Akakin, Dilek; Dortunc, BetulThe most commonly used surgical technique for repairing segmental nerve defects is autogenous nerve grafting; however, this method causes donor site morbidity. In this study, we sought to produce prefabricated nerve grafts that can serve as a conduit instead of autologous nerve using a controlled release system created with vascular endothelial growth factor (VEGF)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres. The study was performed in vitro and in vivo. For the in vitro studies, VEGF-loaded PLGA microspheres were prepared. Thirty rats were used for the in vivo studies. Vein grafts were sutured between the tibial and peroneal nerves in all animals. Three groups were created, and an epineural window, partial incision, and microsphere application were performed, respectively. Walking track analysis, morphologic, and electron microscopic assessment were performed at the end of the eight weeks. Microspheres were produced in spherical shapes as required. Controlled release of VEGF was achieved during a 30-days period. Although signs of nerve injury occurred initially in the partial incision groups according to the indexes of peroneal and tibial function, it improved gradually. The index values were not affected in the other groups. There were many myelinated fibers with large diameters in the partial incision and controlled release groups, while a few myelinated fibers that passed through vein graft in the epineural window group. Thereby, prefabrication was carried out for the second and third groups. It was demonstrated that nerve graft can be prefabricated by the controlled delivery of VEGF. (c) 2012 Wiley Periodicals, Inc. Microsurgery, 2012.