Browsing by Author "Isoglu, Sevil Dincer"

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Advances in Micelle-based Drug Delivery: Cross-linked Systems
(BENTHAM SCIENCE PUBL LTDEXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES, 2017) Isoglu, Ismail Alper; Ozsoy, Yildiz; Isoglu, Sevil Dincer; 0000-0002-6887-6549; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
There are several barriers that drug molecules encounter in body beginning from kidney filtration and reticulo-endothelial system (RES) clearance to cellular trafficking. Multifunctional nanocarriers have a great potential for the delivery of drugs by enhancing therapeutic activity of existing methodologies. A variety of nanocarriers are constructed by different material types, which have unique physicochemical properties for drug delivery applications. Micelles formed by amphiphilic polymers are one of the most important drug/nanocarrier formulation products, in which the core part is suitable for encapsulation of hydrophobic agent whereas the outer shell can be utilized for targeting the drug to the disease area. Micelles as self-assembled nanostructures may encounter difficulties in biodistribution of encapsulated drugs because they have a tendency to be dissociated in dilution or high ionic strength. Therefore, therapeutic efficiency is decreased and it requires high amount of drug to be administered to achieve more efficient result. To overcome this problem, covalently stabilized structures produced by cross-linking in core or shell part, which can prevent the micelle dissociation and regulate drug release, have been proposed. These systems can be designed as responsive systems in which cross-links are degradable or hydrolysable under specific conditions such as low pH or reductive environment. These are enhancing characteristics in drug delivery because their cleavage allows the release of bioactive agent encapsulated in the carrier at a certain site or time. This review describes the chemical methodologies for the preparation of cross-linked micelles, and reports an update of latest studies in literature.
Advantage of co-culture strategy for targeted cancer treatment and in vitro studies
(ELSEVIERRADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS, 2021) Bayram, Nurun Nisa; Isoglu, Sevil Dincer; Baran, Yael; Ulu, Gizem Tugce; AGÜ, Mühendislik Fakültesi, Malzeme Bilimi ve Nanoteknoloji Mühendisliği Bölümü; Bayram, Nurun Nisa; Isoglu, Sevil Dincer
Advantage of co-culture strategy for targeted cancer treatment and in vitro studies
Antibacterial Bilayered Skin Patches Made of HPMA and Quaternary Poly(4-vinyl pyridine)
(KOREAN FIBER SOC, KOREA SCIENCE TECHNOLOGY CTR #501 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA, 2018) Isoglu, I. Alper; Demirkan, Cemre; Seker, Mine Gul; uzlakoglu, Kadriye; Isoglu, Sevil Dincer; 0000-0002-6887-6549; 0000-0002-6226-7507; 0000-0002-7564-9213; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
This study aimed to produce poly(4-vinyl pyridine) and hydroxypropyl methacrylamide (HPMA)-based bilayer wound dressings materials enhancing healing mechanism for the wounds which have self-healing problem and high infection risk. These materials were designed to protect wound from secondary traumas caused microorganism invasion and do not have toxic substance release problem. Synthesis of quaternary poly(4-vinyl pyridine) (poly(Q4-VP)) which is the antibacterial layer of wound dressing material was carried out in two stages. At first stage, poly(4-vinyl pyridine) polymer was synthesized from 4-vinyl pyridine monomer by free radical polymerization. Then, poly(Q4-VP) was synthesized from poly(4-VP) by alkylation reaction with 6-bromocaproic acid. Resulted polymer was structurally characterized by FT-IR. The macroporous spongy structure, as the lower layer of wound dressing material, was prepared by cryogelation of HPMA. Then, the antibacterial polymer was electrospun onto the cryogel structure and bilayered material was obtained. Cryogel structure, fiber morphology and layer integration was examined by SEM. In order to enhance wound healing process, ascorbic acid (vitamin C) was loaded to cryogel layer and release was followed by spectrophotometrically. The antimicrobial properties of the materials were examined against Escherichia coli, Staphylococcus aureus and Candida albicans, respectively. According to the results, bilayered, antibacterial and antifungal against Staphylococcus aureus and Candida albicans, temporary wound dressings which can stimulate wound healing and have high swelling capacity were obtained successfully.
Core-crosslinking as a pathway to develop inherently antibacterial polymeric micelles
(WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, 2019) Kadayifci, Melike Seyma; Gokkaya, Damla; Topuzogullari, Murat; Isoglu, Sevil Dincer; Atabey, Tugba; Arasoglu, Tulin; Ozmen, Mehmet Murat; 0000-0002-6887-6549; 0000-0002-9330-5107; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
Positively charged polymeric materials have been an alternative to combat bacteria as they exhibit inherently antibacterial potency via bacteria membrane disruption. In this study, we report facile preparation of positively charged core-crosslinked polymeric micelles with inherent antibacterial properties. Spherical micelles were prepared by self-assembling of poly(4-vinylpyridine)-b-(oligoethylene glycol methyl ether methacrylate) copolymer in aqueous solution. Herein, quaternization reaction was utilized for the first time to core crosslink the micelles through the pyridine rings utilizing their hydrophobic core and thus resulting positively charged nanostructures. Dynamic light scattering (DLS) results identified that the micelles have an average hydrodynamic diameter of 114 nm with a polydispersity index ranging between 0.105 and 0.114. The electrophoretic light scattering (ELS) measurements demonstrated that the micelles have zeta potential values ranging from +38 to +63 mV. It was evident from both ELS and DLS results that the micelles in solution exhibit long-term stability as the samples were able to maintain their size and charge even after a year of storage. Further, the micelles exhibited inherently antibacterial activity against Escherichia coli and furthermore, this antibacterial efficacy was sustained over a period of 1 year. These stable core-crosslinked micelles are proposed to have great potential as antibacterial materials for long-term applications. (c) 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48393.
Determination of therapeutic effects of multifunctional micelle-based nanocarriers on breast cancer cells
(ELSEVIERRADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS, 2021) Ulu, G. T.; Bayram, Nurun Nisa; Abdulhadi, N.; Gurdap, Seda; Isoglu, A.; Isoglu, Sevil Dincer; Baran, Yael; 0000-0002-8697-1654; 0000-0001-9265-9985; AGÜ, Mühendislik Fakültesi, Malzeme Bilimi ve Nanoteknoloji Mühendisliği Bölümü; Bayram, Nurun Nisa; Gurdap, Seda; Isoglu, A.; Isoglu, Sevil Dincer
Determination of therapeutic effects of multifunctional micelle-based nanocarriers on breast cancer cells
HER2-Targeted, Degradable Core Cross-Linked Micelles for Specific and Dual pH-Sensitive DOX Release
(WILEY-V C H VERLAG GMBHPOSTFACH 101161, 69451 WEINHEIM, GERMANY, 2021) Bayram, Nazende Nur; Ulu, Gizem Tugce; Topuzogullari, Murat; Baran, Yusuf; Isoglu, Sevil Dincer; 0000-0002-8697-1654; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Bayram, Nazende Nur; Isoglu, Sevil Dincer
Here, a targeted, dual-pH responsive, and stable micelle nanocarrier is designed, which specifically selects an HER2 receptor on breast cancer cells. Intracellularly degradable and stabilized micelles are prepared by core cross-linking via reversible addition-fragmentation chain-transfer (RAFT) polymerization with an acid-sensitive cross-linker followed by the conjugation of maleimide-doxorubicin to the pyridyl disulfide-modified micelles. Multifunctional nanocarriers are obtained by coupling HER2-specific peptide. Formation of micelles, addition of peptide and doxorubicin (DOX) are confirmed structurally by spectroscopical techniques. Size and morphological characterization are performed by Zetasizer and transmission electron microscope (TEM). For the physicochemical verification of the synergistic acid-triggered degradation induced by acetal and hydrazone bond degradation, Infrared spectroscopy and particle size measurements are used. Drug release studies show that DOX release is accelerated at acidic pH. DOX-conjugated HER2-specific peptide-carrying nanocarriers significantly enhance cytotoxicity toward SKBR-3 cells. More importantly, no selectivity toward MCF-10A cells is observed compared to HER2(+) SKBR-3 cells. Formulations cause apoptosis depending on Bax and Caspase-3 and cell cycle arrest in G2 phase. This study shows a novel system for HER2-targeted therapy of breast cancer with a multifunctional nanocarrier, which has higher stability, dual pH-sensitivity, selectivity, and it can be an efficient way of targeted anticancer drug delivery.
Preparation and Characterization of Viburnum Opulus Containing Electrospun Membranes as Antibacterial Wound Dressing
(KOREAN FIBER SOC, 2023) Yuruk, Adile; Isoglu, Sevil Dincer; Isoglu, Ismail Alper; 0000-0003-1611-9105; 0000-0002-6887-6549; 0000-0001-6428-4207; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Yuruk, Adile; Isoglu, Sevil Dincer; Isoglu, Ismail Alper
Herein, we fabricated polycaprolactone/gelatin electrospun membranes possessing different amounts of Viburnum Opulus extract (0, 25, 35, 50%, w/v) as an antibacterial wound dressing. We investigated chemical, morphological, physical, and mechanical properties as well as in vitro degradation behavior of the electrospun membranes. The antibacterial activities of membranes were evaluated against gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli). The membranes containing Viburnum Opulus exhibited excellent antibacterial activity with the formation of inhibition zones of 25 mm to 36 mm against Escherichia coli and 14 mm to 25 mm against Staphylococcus aureus. The fiber diameters rose from 591 to 1222 nm after adding Viburnum Opulus extract. The extract-containing membranes displayed superior swelling, cell viability, and proliferation properties to neat membranes. Our results showed that the polycaprolactone/gelatin electrospun membranes containing Viburnum Opulus could be a suitable material for wound dressing applications.
Preparation of antibacterial electrospun poly(D, L-lactide-co-glycolide)/gelatin blend membranes containing Hypericum capitatum var. capitatum
(TAYLOR & FRANCIS AS, KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY, 2020) Aksit, Nazende Nur; Gurdap, Seda; Isoglu, Sevil Dincer; Isoglu, Ismail Alper; 0000-0002-6887-6549; 0000-0001-6428-4207; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
In this study, we fabricated poly(D, L-lactide-co-glycolide)/gelatin (PLGA/gelatin) membranes containing different amounts of Hypericum capitatum var. capitatum (HCC) extract (1, 5, 7.5, 10 wt%) by electrospinning technique. We investigated chemical, morphological, physical, and mechanical properties as well as in vitro degradation behavior of the electrospun membranes. We also evaluated the antibacterial activity of the electrospun membranes against Escherichia coli and Staphylococcus aureus. Viability, adhesion, and attachment of human fibroblast cells on the electrospun membranes on pre-set days were evaluated by the colorimetric CellTiter 96(R) AQueous One Solution Cell Proliferation Assay (MTS assay), scanning electron microscopy (SEM), and 4',6-Diamidino-2-Phenylindole (DAPI) staining.
RAFT-synthesized POEGMA-b-P4VP block copolymers: preparation of nanosized micelles for anticancer drug release
(SPRINGERONE NEW YORK PLAZA, SUITE 4600 , NEW YORK, NY 10004, UNITED STATES, 2021) Bayram, Nazende Nur; Topuzogullari, Murat; Isoglu, Ismail Alper; Isoglu, Sevil Dincer; 0000-0002-8697-1654; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Bayram, Nazende Nur; Isoglu, Ismail Alper; Isoglu, Sevil Dincer
To achieve high stability and biocompatibility in physiological environment, oligoethyleneglycol methacrylate (OEGMA) and 4-vinylpyridine (4VP)-based amphiphilic block copolymers were prepared as micellar carriers to deliver doxorubicin into tumor cells. First, macroinitiator of OEGMA was synthesized by RAFT polymerization at [M](0)/[CTA](0)/[I](0) ratio of 100/1/0.2 in dimethylformamide (DMF) at 70 degrees C, in the presence of 4,4'-azobis(4-cyanovaleric acid) (ACVA) as initiator and 4-cyano-4-(thiobenzoylthio)pentanoic acid (CTA) as chain transfer agent, respectively. It was followed by copolymerization with 4-VP at similar conditions. The formation of RAFT-mediated polymers was approved by FTIR, H-1-NMR and GPC. For the preparation of drug-loaded micelles, a dialysis method was applied and hydrophobic doxorubicin, as a model drug, was entrapped into the micelles. Size distributions and morphologies of drug-loaded micelles were investigated by light scattering and scanning electron microscopy, respectively. Critical micelle concentration was estimated as 0.0019 mg/mL by measuring light scattering intensity in different polymer concentrations. Also, drug loading and entrapment efficiencies were calculated as 4.41% and 17.65% by measuring the DOX amount in the micelles, spectrophotometrically. At last, the drug-loaded micelles were applied to SKBR-3 breast cancer cell lines and revealed up to %40 cell inhibition at 48 and 72 h. As a result, these nanosized and biocompatible micelles can be used for the delivery of hydrophobic drugs, and they can also be modified for further targeting and imaging applications toward specific cancer cells.
Thermo-Responsive Complexes of c-Myc Antisense Oligonucleotide with Block Copolymer of Poly(OEGMA) and Quaternized Poly(4-Vinylpyridine)
(WILEY-V C H VERLAG GMBHPOSTFACH 101161, 69451 WEINHEIM, GERMANY, 2017) Topuzogullari, Murat; Elalmis, Yeliz Basaran; Isoglu, Sevil Dincer; 0000-0002-6871-2202; 0000-0003-4435-7776; 0000-0002-6887-6549; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
Solution behavior of thermo-responsive polymers and their complexes with biological macromolecules may be affected by environmental conditions, such as the concentration of macromolecular components, pH, ion concentration, etc. Therefore, a thermo-responsive polymer and its complexes should be characterized in detail to observe their responses against possible environments under physiological conditions before biological applications. To briefly indicate this important issue, thermo-responsive block copolymer of quaternized poly(4-vinylpyridine) and poly(oligoethyleneglycol methyl ether methacrylate) as a potential nonviral vector has been synthesized. Polyelectrolyte complexes of this copolymer with the antisense oligonucleotide of c-Myc oncogene are also thermo-responsive but, have lower LCST (lower critical solution temperature) values compared to individual copolymer. LCST values of complexes decrease with molar ratio of macromolecular components and presence of salt. Dilution of solutions also affects solution behavior of complexes and causes a significant decrease in size and an increase in LCST, which indicates possible effects of severe dilutions in the blood stream.