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    Clindamycin phosphate and bone morphogenetic protein-7 loaded combined nanoparticle-graft and nanoparticle-film formulations for alveolar bone regeneration – An in vitro and in vivo evaluation
    (Elsevier B.V., 2023) Ilhan, Miray; Kilicarslan, Muge; Alcigir, Mehmet Eray; Bagis, Nilsun; Ekim, Okan; Orhan, Kaan
    Commonly utilized techniques for healing alveolar bone destruction such as the use of growth factors, suffering from short half-life, application difficulties, and the ability to achieve bioactivity only in the presence of high doses of growth factor. The sustained release of growth factors through a scaffold-based delivery system offers a promising and innovative tool in dentistry. Furthermore, it is suggested to guide the host response by using antimicrobials together with growth factors to prevent recovery and achieve ideal regeneration. Herein, the aim was to prepare and an in vitro - in vivo evaluation of bone morphogenetic protein 7 (BMP-7) and clindamycin phosphate (CDP) loaded polymeric nanoparticles, and their loading into the alginate-chitosan polyelectrolyte complex film or alloplastic graft to accelerate hard tissue regeneration. PLGA nanoparticles containing CDP and BMP-7, separately or together, were prepared using the double emulsion solvent evaporation technique. Through in vitro assays, it was revealed that spherical particles were homogeneously distributed in the combination formulations, and sustained release could be achieved for >12 weeks with all formulations. Also, results from the micro-CT and histopathological analyses indicated that CDP and BMP-7 loaded nanoparticle-film formulations were more effective in treatment than the nanoparticle loaded grafts. © 2023 Elsevier B.V.
  • [ X ]
    Öğe
    Clindamycin phosphate and bone morphogenetic protein-7 loaded combined nanoparticle-graft and nanoparticle-film formulations for alveolar bone regeneration-An in vitro and in vivo evaluation
    (Elsevier, 2023) Ilhan, Miray; Kilicarslan, Muge; Alcigir, Mehmet Eray; Bagis, Nilsun; Ekim, Okan; Orhan, Kaan
    Commonly utilized techniques for healing alveolar bone destruction such as the use of growth factors, suffering from short half-life, application difficulties, and the ability to achieve bioactivity only in the presence of high doses of growth factor. The sustained release of growth factors through a scaffold-based delivery system offers a promising and innovative tool in dentistry. Furthermore, it is suggested to guide the host response by using antimicrobials together with growth factors to prevent recovery and achieve ideal regeneration. Herein, the aim was to prepare and an in vitro -in vivo evaluation of bone morphogenetic protein 7 (BMP-7) and clindamycin phosphate (CDP) loaded polymeric nanoparticles, and their loading into the alginate-chitosan polyelectrolyte complex film or alloplastic graft to accelerate hard tissue regeneration. PLGA nanoparticles containing CDP and BMP-7, separately or together, were prepared using the double emulsion solvent evaporation technique. Through in vitro assays, it was revealed that spherical particles were homogeneously distributed in the combination formulations, and sustained release could be achieved for >12 weeks with all formulations. Also, results from the micro-CT and histopathological analyses indicated that CDP and BMP-7 loaded nanoparticle-film formulations were more effective in treatment than the nanoparticle loaded grafts.
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    Clinicopathological and immunohistochemical evaluation of lonidamine-entrapped lipid-polymer hybrid nanoparticles in treatment of benign prostatic hyperplasia: An experimental rat model
    (ELSEVIER, 2020) Sengel-Turk, Ceyda Tuba; Alcigir, Mehmet Eray; Ekim, Okan; Bakar-Ates, Filiz; Hascicek, Canan
    Benign prostatic hyperplasia (BPH) is a progressive proliferative disease, the incidence of which is constantly increasing due to aging of population. In this research, a hexokinase-II enzyme inhibiting agent, lonidamine - the use of which is limited in BPH treatment due to high hepatic toxicity observed after three months of treatment - was selected as an active agent, based on its mechanism of action in treating BPH. The aim of this study was to evaluate in vivo therapeutic efficacy and hepatic toxicity of lipid-polymer hybrid nanoparticles of lonidamine in a rat BPH model created in rat prostates. After local injections of hybrid nanoparticles of lonidamine were administered to the rat prostates, hyperplasic structures of prostates were evaluated in terms of prostatic index values, immunohistochemical evaluations, and histopathological findings. Liver blood enzyme values were also determined to specify hepatic toxicity. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) reaction and histopathological methods to determine intravital degenerative destruction in liver. Through this study, lonidamine-loaded hybrid nanoparticles were found to reduce the he-patic toxicity and increase therapeutic efficiency of lonidamine. Therefore, lonidamine-entrapped hybrid nanoparticles may provide a promising, and very safe, drug delivery strategy in the treatment of BPH.
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    Effects of Lonidamine-Loaded Lipid-Polymer Hybrid Nanoparticles on Cardiac Fibrosis Induced By High-Dose Testosterone Propionate In Adult and Neutered Male Rats
    (2018) Alçığır, Mehmet Eray; Türk, Ceyda Tuba Şengel; Hasçiçek, Canan; Ekim, Okan
    In recent years, the usage of exogenous testosterone has tripled in humans. Although, mechanism has not yet been fullyelucidated, there is a correlation between the increased risk of heart failure and testosterone usage. The aim of this studywas to demonstrate cardiac fibrosis, which a main finding of hearth failure, in testosterone propionate-applied male ratsand to show its regression by Lonidamine as an anti-hyperplastic agent. A total of 72 adult Wistar albino and neutralizedmale rats were divided into 4 groups (n=18 in each groups). Animals in all groups were received to testosterone propionateuntil 2nd, 4th, and 12th weeks (n=6 in each groups). Subsequently, group I and II also received the pure solution ofLonidamine hydrochloride and its lipid-polymer hybrid nanoparticulate formulation via intraprostatic injection. Group III,blank lipid-polymer hybrid nanoparticle formulation were solely administrated via same way. The control group or groupIV were received only testosterone. At the end of the experiment period, hearts were collected and fibrocytic changes wereconfirmed by histochemical and immunohistochemical methods. Histopathologically, fibrosis were lower in group I and IIwhen comprared to that of group III and IV. Imunohistochemically, bFGF, cyclin D1 and p16 protein expressions wereevaluated. bFGF and cyclinD1 epxressions correspondingly to increasing fibrosis were found higher in last two groupsduring the experiment. But, p16 expressions were lower in Lonidamine treated-group I and II. In conclusion, results ofthis study supported that testosterone propionate may promote cardiac fibrosis. Lonidamine hydrochloride may be used inits prevention of fibrosis.
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    Morphological pattern of the pes tendons in Bennett's Wallaby (Macropus rufogriseus)
    (Wiley, 2022) Yunus, Hasen Awel; Ekim, Okan; Bakici, Caner; Bakici, Merve; Batur, Baris
    Wallabies are small- to medium-sized hopping marsupials and have large and flexible tendons in their hind limbs that act like springs. This study aimed to show the morphological pattern of the pes tendons in Bennett's wallaby. Two Bennett's Wallabies (Macropus rufogriseus) that died of natural causes have been used for this study. The pes was dissected using standard dissection techniques to expose the tendons around metatarsals and digits. The crural musculature of the hind limb was also dissected to identify the origin of the tendons. Tendons of m. extensor digitorum longus, m. extensor digitorum lateralis, m. extensor digiti II et III longus, m. flexor digitorum superficialis, m. flexor digitorum profundus and mm. interossei were the main identified tendons. Tendons of m. extensor digitorum longus attached to the distal phalanx of the fourth digit. The tendon of m. extensor digitorum lateralis had two insertion points, on the fourth and the fifth digits. The tendon of m. flexor digitorum superficialis bifurcates at the level proximal one-third of the metatarsus. The relatively thinner branch inserted into the phalanx of the fifth digit, while the thicker splits and inserted to the medial and lateral surface of the distal end of the proximal phalanx of the fourth digit. Tendon of m. flexor digitorum profundus was the thickest tendon on the plantar surface, and it had four insertion points, which were the distal phalanges of the second, third, fourth and fifth digits. This study provides detailed information for future studies on the biomechanical and functional morphology of tendons in marsupials.