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Antitumor efficacy of bacillus calmette-guerin loaded cationic nanoparticles for intravesical immunotherapy of bladder tumor induced rat model

Erdoğar N. | Iskit A.B. | Eroğlu H. | Sargon M.F. | Mungan N.A. | Bilensoy E.

Article | 2015 | Journal of Nanoscience and Nanotechnology15 ( 12 ) , pp.10156 - 10164

For bladder cancer, intravesical chemo/immunotherapy is widely used as adjuvant therapy after surgical transurethral resection. Bacillus Calmette-Guerin (BCG) is a live attenuated Mycobacterium of the same family as tuberculosis, that is capable of inducing a local inflammatory response upon instillation into the bladder. Intravesical therapy with BCG has proved to be more effective in the prophylaxis and treatment of superficial bladder tumors than most chemotherapeutic agents used for the same indication. However, compared to intravesical chemotherapy, BCG immunotherapy provokes more pronounced local and systemic reactions. In add . . .ition to the commonly induced granulomatous inflammatory changes in the bladder, which produce irritative symptoms, this therapy may cause systemic side effects varying from mild malaise and fever to, in rare instances, lifethreatening or fatal sepsis. Nanoparticles with positive surface charge and mucoadhesive properties were developed to overcome these side effects. Hence, the aim of this study was to optimize and evaluate cationic chitosan (CS) nanoparticles encapsulating BCG in terms of antitumor efficacy after intravesical administration in bladder tumor, induced in rat model. It was found that nanoparticle formulations of 269-375 nm in size can be produced with 42% encapsulation efficiency. The zeta potential was positive and was suitable for intravesical administration. Antitumor efficacy was determined over the parameters of histopathological evaluation, survival rate and mean bladder weight in comparison to treatment with commercial BCG solution. Concerning survival rates, BCG-loaded chitosan nanoparticles resulted in significantly longer survival than BCG commercial product (up to 86 days of survival with no systemic side effects). When compared to healthy bladder weight averages, all groups (especially BCG commercial solution) showed higher bladder weights confirming tumor formation. Histopathological findings confirmed antitumor activity in all treatment groups and optimum findings were observed in groups treated with CS nanoparticles encapsulating BCG. At the same time, significant nanoparticle accumulation in bladder tissues was observed especially for BCG-loaded CS group. In this study, it was clearly observed that cationic CS nanoparticles provide a significantly improved perspective in intravesical immunotherapy of bladder tumors. Copyright © 2015 American Scientific Publishers Daha fazlası Daha az

Antibacterial chitosan/silk sericin 3D porous scaffolds as a wound dressing material

Karahaliloglu Z. | Kilicay E. | Denkbas E.B.

Article | 2017 | Artificial Cells, Nanomedicine and Biotechnology45 ( 6 ) , pp.1172 - 1185

Antimicrobial mixed dressings have traditionally been used to minimize bacterial infection of burns and other wounds. This study presents the advancement of biocompatible chitosan/silk sericin (CHT/SS) scaffolds combined with lauric acid (LA) and zinc oxide nanoparticles (nZnO) for the successful wound dressing applications. Antibacterial assay results showed that the diameters of the inhibition zone increased from 2 ± 0.4 to 7 ± 0.1 mm for Escherichia coli, as well as from 2.5 ± 0.2 to 6 ± 0.4 mm for Staphylococcus aureus while CHTS/SS/100nZnO compared to CHT/SS/0.01LA. The results not only showed excellent inhibition against Gram- . . .positive and Gram-negative bacterial growth but also revealed improved proliferation and extended viability for HaCaT cells. © 2016 Informa UK Limited, trading as Taylor & Francis Group Daha fazlası Daha az

Cationic core-shell nanoparticles for intravesical chemotherapy in tumor-induced rat model: Safety and efficacy

Erdogar N. | Iskit A.B. | Eroglu H. | Sargon M.F. | Mungan N.A. | Bilensoy E.

Article | 2014 | International Journal of Pharmaceutics471 ( 01.Feb ) , pp.1 - 9

Mitomycin C (MMC) has shown potent efficacy against a wide spectrum of cancers and is clinical first choice in superficial bladder tumors. However, intravesical chemotherapy with MMC has been ineffective due to periodical discharge of the bladder and instability of this drug in acidic pH, both resulting in high rate of tumor recurrence and insufficiency to prevent progression. Nanocarriers may be a promising alternative for prolonged, effective and safe intravesical drug delivery due to their favorable size, surface properties and optimum interaction with mucosal layer of the bladder wall. Hence, the aim of this study was to evaluat . . .e and optimize cationic core-shell nanoparticles formulations (based on chitosan (CS) and poly-µ-caprolactone (PCL)) in terms of antitumor efficacy after intravesical administration in bladder tumor induced rat model. Antitumor efficacy was determined through the parameters of survival rate and nanoparticle penetration into the bladder tissue. Safety of the formulations were evaluated by histopathological evaluation of bladder tissue as well as observation of animals treated with MMC bound to nanoparticles. Results indicated that chitosan coated poly-µ-caprolactone (CS-PCL) nanoparticles presented the longest survival rate among all treatment groups as evaluated by Kaplan-Meier plotting. Histopathological evaluation revealed that cationic nanoparticles were localized and accumulated in the bladder tissue. As intravesical chemotherapy is a local therapy, no MMC was quantified in blood after intravesical instillation indicating no systemic uptake for the drug which could have subsequently led to side effects. In conclusion, core-shell type cationic nanoparticles may be effective tools for the intravesical chemotherapy of recurrent bladder tumors. © 2014 Elsevier B.V Daha fazlası Daha az

Grafting of poly(3-hydroxyalkanoate) and linoleic acid onto chitosan

Arslan, Hülya | Hazer, Baki | Yoon, Sung C.

Article | 2007 | Journal of Applied Polymer Science103 ( 1 ) , pp.81 - 89

Poly(3-hydroxy octanoate) (PHO), poly(3-hydroxy butyrate-co-3- hydroxyvalerate) (PHBV), and linoleic acid were grafted onto chitosan via condensation reactions between carboxylic acids and amine groups, Unreacted PHAs and linoleic acid were eliminated via chloroform extraction and for elimination of unreacted chitosan were used 2 wt % of HOAc solution. The pure chitosan graft copolymers were isolated and then characterized by FTIR, 13C-NMR (in solid state), DSC, and TGA. Microbial polyester percentage grafted onto chitosan backbone was varying from 7 to 52 wt % as a function of molecular weight of PHAs, namely as a function of steri . . .c effect. Solubility tests were also performed. Graft copolymers were soluble, partially soluble or insoluble in 2 wt % of HOAc depending on the amount of free primary amine groups on chitosan backbone or degree of grafting percent. Thermal analysis of PHO-g-Chitosan graft copolymers indicated that the plastizer effect of PHO by means that they showed melting transitions Tms at 80, 100, and 113°C or a broad Tms between 60.5-124.5°C and 75-125°C while pure chitosan showed a sharp Tm at 123°C. In comparison of the solubility and thermal properties of graft copolymers, linoleic acid derivatives of chitosan were used. Thus, the grafting of poly(3-hydroxyalkanoate) and linoleic acid onto chitosan decrease the thermal stability of chitosan backbone. © 2006 Wiley Periodicals, Inc Daha fazlası Daha az

Synthesis and properties of chitosan-modified poly(vinyl butyrate)

Akgün, Sibel | Ekici, Gülsüm | Mutlu, Nilüfer | Beşirli, Necati | Hazer, Baki

Article | 2007 | Journal of Polymer Research14 ( 3 ) , pp.215 - 221

Modification of chitosan by grafting of vinyl butyrate was carried out in homogeneous phase using potassium persulfate as redox initator and 1.5% acetic acid as solvent. The percent grafting and grafting efficiency were analysed and the high grafting efficiency up to 94% was observed. The effects of reaction variables such as monomer concentration, initiator concentration, temperature and reaction time were investigated. It was observed that the solubility of chitosan was markedly reduced after grafting with vinyl butyrate. The grafted product is insoluble in common organic solvents as well in dilute organic and inorganic acids. Cha . . .racterization of the graft copolymers were carried out by using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and Scanning Electron Microscopy (SEM) technics. Characteristic signal of carbonyl group was observed at 1,731 cm-1 which belongs to the poly vinyl butyrate segments in the graft copolymer. The melting transition of the chitosan main chain in the copolymer shifted to 124°C from its original value 101°C. In addition to these, we have also studied topology of the graft copolymer and the SEM micrograph showed continuous homogenous matrix which means there is no phase separation. © Springer Science+Business Media B.V. 2007 Daha fazlası Daha az

Intravesical cationic nanoparticles of chitosan and polycaprolactone for the delivery of Mitomycin C to bladder tumors

Bilensoy, Erem | Sarisozen, Can | Esendagli, Guenes | Dogan, A. Lale | Aktas, Yesim | Sen, Murat | Mungan, N. Aydin

Article | 2009 | INTERNATIONAL JOURNAL OF PHARMACEUTICS371 ( 01.Feb ) , pp.170 - 176

Cationic nanoparticles of chitosan (CS), poly-epsilon-caprolactone coated with chitosan (CS-PCL) and poly-e-caprolactone coated with poly-L-lysine (PLL-PCL) were developed to encapsulate intravesical chemotherapeutic agent Mitomycin C (MMC) for longer residence time, higher local drug concentration and prevention of drug loss during bladder discharge. Nanoparticle diameters varied between 180 and 340 nm depending on polymer used for preparation and coating. Zeta potential values demonstrated positive charge expected from cationic nanoparticles. MMC encapsulation efficiency depended on hydrophilicity of polymers since MMC is water-so . . .luble. Encapsulation was increased by 2-fold for CS-PCL and 3-fold for PLL-PCL as a consequence of hydrophilic coating. Complete drug release was obtained with only CS-PCL nanoparticles. On the other hand, CS and PLL-PCL nanoparticles did not completely liberate MMC due to strong polymer-drug interactions which were elucidated with DSC studies. As far as cellular interaction was concerned, CS-PCL was the most efficient formulation for uptake of fluorescent markers Nile Red and Rhodamine123 incorporated into nanoparticles. Especially, CS-PCL nanoparticles loaded with Rhodamine123 sharing hydrophilic properties with MMC were selectively incorporated by bladder cancer cell line, but not by normal bladder epithelial cells. CS-PCL nanoparticles seem to be promising for MMC delivery with respect to anticancer efficacy tested against MB49 bladder carcinoma cell line. (C) 2008 Elsevier B.V. All rights reserved Daha fazlası Daha az

Encapsulated boron as an osteoinductive agent for bone scaffolds

Gumusderelioglu M. | Tunçay E.T. | Kaynak G. | Demirtaş T.T. | Aydin S.T. | Hakki S.S.

Article | 2015 | Journal of Trace Elements in Medicine and Biology31 , pp.120 - 128

The aim of this study was to develop boron (B)-releasing polymeric scaffold to promote regeneration of bone tissue. Boric acid-doped chitosan nanoparticles with a diameter of approx. 175. nm were produced by tripolyphosphate (TPP)-initiated ionic gelation process. The nanoparticles strongly attached via electrostatic interactions into chitosan scaffolds produced by freeze-drying with approx. 100. µm pore diameter. According to the ICP-OES results, following first 5. h initial burst release, fast release of B from scaffolds was observed for 24. h incubation period in conditioned medium. Then, slow release of B was performed over 120. . . . h. The results of the cell culture studies proved that the encapsulated boron within the scaffolds can be used as an osteoinductive agent by showing its positive effects on the proliferation and differentiation of MC3T3-E1 preosteoblastic cells. © 2015 Elsevier GmbH Daha fazlası Daha az

Comparison of the efficiencies of buffers containing ankaferd and chitosan on hemostasis in an experimental rat model with femoral artery bleeding

Abacıoğlu, Serkan | Aydın, Kemal | Büyükcam, Fatih | Kaya, Ural | Işık, Bahattin | Karakılıç, Muhammed Evvah

Article | 2016 | TURKISH JOURNAL OF HEMATOLOGY33 ( 1 ) , pp.48 - 52

Objective: In the first assessment of trauma patients with major vascular injuries, we need effective and rapid-acting homeostatic materials. In this study we compare the efficiencies of Ankaferd Blood Stopper (R) and a chitosan linear polymer (Celox (R)) in an experimental rat model with femoral artery bleeding. Materials and Methods: Thirty male Wistar albino rats weighing 200250 g were divided into 3 groups: control, Ankaferd, and chitosan. The femoral artery and vein were visualized and bleeding was started by an incision. The bleeding time was recorded and categorized as 'bleeding stopped at the second minute', 'bleeding stoppe . . .d at the fourth minute', and 'unsuccessful' if bleeding continued after the fourth minute. Results: In the control group, 60% of the bleeding did not stop. In the first 4 min in the Ankaferd group, the bleeding stopped in all rats; only in 1 of the rats in the chitosan group did the bleeding not stop. In stopping the bleeding in the first 4 min, Ankaferd was similar to chitosan but better than the control group; the chitosan group was similar to the control, but the p-value was close to significance. Conclusion: For major arterial bleeding, the main treatment is surgical bleeding control, but outside of the hospital we can use buffers containing Ankaferd and chitosan on the bleeding region. The results of this study should be supported with larger studies. Furthermore, in our study, healthy rats were used. New studies are needed to evaluate the results of hypovolemic and hypotensive cases with major artery bleeding Daha fazlası Daha az

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