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    Development and characterization of oxaceprol-loaded poly-lactide-co-glycolide nanoparticles for the treatment of osteoarthritis
    (Wiley, 2020) Alarcin, Emine; Demirbag, Caglar; Karsli-Ceppioglu, Seher; Kerinnoglu, Oya; Bal-Ozturk, Ayca
    Oxaceprol is well-defined therapeutic agent as an atypical inhibitor of inflammation in osteoarthritis. In the present study, we aimed to develop and characterize oxaceprol-loaded poly-lactide-co-glycolide (PLGA) nanoparticles for intra-articular administration in osteoarthritis. PLGA nanoparticles were prepared by double-emulsion solvent evaporation method. Meanwhile, a straightforward and generally applicable high performance liquid chromatography method was developed, and validated for the first time for the quantification of oxaceprol. To examine the drug carrying capacity of nanoparticles, varying amount of oxaceprol was entrapped into a constant amount of polymer matrix. Moreover, the efficacy of drug amount on nanoparticle characteristics such as particle size, zeta potential, morphology, drug entrapment, and in vitro drug release was investigated. Nanoparticle sizes were between 229 and 509 nm for different amount of oxaceprol with spherical smooth morphology. Encapsulation efficiency ranged between 39.73 and 63.83% by decreasing oxaceprol amount. The results of Fourier transform infrared and DSC showed absence of interaction between oxaceprol and PLGA. The in vitro drug release from these nanoparticles showed a sustained release of oxaceprol over 30 days. According to cell culture studies, oxaceprol-loaded nanoparticles had no cytotoxicity with high biocompatibility. This study was the first step of developing an intra-articular system in the treatment of osteoarthritis for the controlled release of oxaceprol. Our findings showed that these nanoparticles can be beneficial for an effective treatment of osteoarthritis avoiding side effects associated with oral administration.
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    Evaluation of biochemical parameters inRubus tereticaulistreated rats and its implications in wound healing
    (Springer, 2020) Aksoy, Halil; Demirbag, Caglar; Sen, Ali; Sekerler, Turgut; Ozakpinar, Ozlem; Sener, Azize; Ahmad, Sarfraz
    We evaluated the effects ofRubus tereticaulisin healing process by determining the total carbonyl content, collagen synthesis, and total protein level on rat wounded tissues. Wounds were performed in the back of 54 Wistar rats, using a biopsy punch instrument with 0.6 mm in diameter. Rats were randomly divided into three groups: (i) un-treatment wounds group served as controls, (ii) Madecassol (R) used as positive control group, and (iii) the application of topical cream ofR. tereticaulisserved as treatment group of wound healing. The animals were killed at the end of experiment under anesthesia with ketamine, and tissue samples were collected for the evaluation at three times intervals (3rd, 7th, and 14th day). The wounded areas were analyzed for total carbonyl content, collagen, and total protein levels by HPLC, ELISA, and spectrophotometric methods, respectively. Total carbonyl content in the treatment group was significantly lower in comparison with control group on 3rd day (2.839 +/- 0.438 vs. 3.216 +/- 0.216 nmol carbonyl/mol protein;p < 0.5) and 14th days (4.222 +/- 0.128 vs. 4.784 +/- 0.077 nmol carbonyl/mol protein;p < 0.05), respectively. New collagen formation on the wound sites after the initial injury was noted in the treated and positive control groups (5.310 +/- 0.331 vs. 5.164 +/- 0.377 mg collagen/g wet tissue) at the 3rd day than control group (2.180 +/- 0.718 mg collagen/g wet tissue,p < 0.01), and in treated and positive control groups at 7th day (9.654 +/- 0.201, 9.053 +/- 1.062 mg collagen/g wet tissue,p < 0.01); and in treated and positive control groups at 14th day (8.469 +/- 0.236, 5.631 +/- 0.531 mg collagen/g wet tissue, respectively;p < 0.05) in comparison with the control group. Total protein level of samples did not change significantly between the groups. Thus, application ofR. tereticaulisameliorated the wound healing process in rats as it facilitated collagen formation through healing of the wound. Evaluating total carbonyl content by HPLC could be useful as an advance procedure for quantification of healing.
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    Improving the Bioavailability and Efficacy of Coenzyme Q10 on Alzheimer's Disease Through the Arginine Based Proniosomes
    (Elsevier Science Inc, 2023) Ergin, Ahmet Dogan; Uner, Burcu; Balcib, Sencan; Demirbag, Caglar; Benetti, Camillo; Oltulu, Cagatay
    Coenzyme Q10 (CoQ10) is a fat-soluble vitamin-with a benzoquinone-like structure. CoQ10 plays a role in membrane stability, energy conversion, and ATP production. It is also one of the important antioxidants in the body. The bioavailability of exogenous CoQ10 is extremely low due to its poor aqueous solubility and large molecular mass.In this study, mixed proniosomal drug delivery systems have been used to increase solubility and bioavailability of CoQ10. Arginine (semi-essential amino acid) was incorporated in the formulation composition to achieve higher efficacy by boosting nitric oxide presence, endothelial dysfunction, and cellular uptake.Proniosomes were investigated in terms of particle size, polydispersity index, zeta potential, encapsulation efficiency, and process yield, and optimization studies were carried on by utilizing STATISTICA 8.0 software considering dependent factors (carrier amount, drug amount, and surfactant ratio). Optimum proniosome formulation (particle size 187.5 +/- 16.35 nm, zeta potential: -44.7 +/- 12.8 mV, encapsulation efficiency 99.05 +/- 0.30%, and product yield: 90.55%) was evaluated for thermal analysis, in-vitro drug release using microcentrifuge method. In-vitro cytotoxicity studies of proniosomes were performed on intestinal Epithelial Cells (Cellartis (R), ChiPSC18) and no cytotoxic effects was seen during the 72 h. Besides, anti Alzheimer effect was investigated on APPSL-GFP lentivirus-infected human neural cells (APPSL-GFP-l-HNC) and Alzheimer biomarkers (p-tau181 and p-tau217).While CoQ10's relative bioavailability was statistically increased by proniosome compared to CoQ10 suspension (p<0.01, Grubb test). PK parameters of proniosome formulation, obtained with non-compartmental modeling, were fitting to the data (R-2=0.956 +/- 0.026).The study results proved that proniosomal formulation has a high potential drug delivery system for both increasing bioavailability and anti-Alzheimer effect of CoQ10.(c) 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
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    Pomegranate Peel Extract Reduces Cisplatin-Induced Toxicity and Oxidative Stress in Primary Neuron Culture
    (Marmara Univ, Inst Health Sciences, 2021) Cinar, Irfan; Yayla, Muhammed; Demirbag, Caglar; Binnetoglu, Damla
    Objective: Cancer is the most common cause of death after cardiovascular diseases. Cisplatin used in most types of cancer produces neurotoxicity. In this study, we aimed to investigate the effects of pomegranate peel extract (1) in different doses, as potent antioxidants, on the prevention of neurotoxicity due to cisplatin, which is frequently used in cancer treatment. Methods: In our study, newborn rat cortex was used. 2 hours following the application of PPE at 200, 300 and 400 mg/mL, neurotoxicity was established by applying cisplatin in 50 and 100 mu M concentrations. Results: In our study, cisplatin decreased cell viability in increasing doses, while PPE showed the best neuroprotective effect in high doses. Increased total oxidant capacity due to toxicity was significantly improved by PPE4. The antioxidant capacity decreased in the toxicity group showed improvement with the administration of PPE4. At the same time, increased TNF-alpha mRNA expression after cisplatin administration was significantly reduced with the administration of PPE4. The increased caspase 3 (CAS 3) and caspase 9 (CAS 9) mRNA expression due to cisplatin showed improvement with the administration of PPE4. Conclusion: These results indicated that PPE could inhibit cisplatin-induced neurotoxicity, and these effects may be related to anti-apoptotic and antioxidants activities.