Browsing by Author "Isoglu, Sevil Dincer"

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Citation - WoS: 34
Citation - Scopus: 38
Advances in Micelle-Based Drug Delivery: Cross-Linked Systems
(Bentham Science Publ Ltd, 2017) Isoglu, Ismail Alper; Ozsoy, Yildiz; Isoglu, Sevil Dincer; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
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.
Citation - WoS: 10
Citation - Scopus: 11
Antibacterial Bilayered Skin Patches Made of HPMA and Quaternary Poly(4-Vinyl Pyridine)
(Korean Fiber Soc, 2018) Isoglu, I. Alper; Demirkan, Cemre; Seker, Mine Gul; Tuzlakoglu, Kadriye; Isoglu, Sevil Dincer; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
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.
Citation - WoS: 11
Citation - Scopus: 13
Core-Crosslinking as a Pathway to Develop Inherently Antibacterial Polymeric Micelles
(Wiley, 2020) Kadayifci, Melike Seyma; Gokkaya, Damla; Topuzogullari, Murat; Isoglu, Sevil Dincer; Atabey, Tugba; Arasoglu, Tulin; Ozmen, Mehmet Murat; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
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.
Enhancing Bioink Potential of Hyaluronic Acid by Microwave-Induced Methacrylation
(Elsevier, 2025) Ishtyah, Yazan R. B.; Cosgun, Seyma Nur Kirmic; Ceylan, Deniz; Demirtas, Tugrul Tolga; Isoglu, Sevil Dincer; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
This study reports the development of a light-curable methacrylated hyaluronic acid (HAMA) synthesized using microwave irradiation. The methacrylation process was carried out with AEMA as the methacrylating agent via an EDC/NHS protocol at varying microwave energy levels and compared comprehensively with those synthesized using the conventional heating method. The HAMA synthesis by microwave was optimized by applying different power levels (100 W, 250 W, and 800 W). The products were characterized by 1H NMR to determine the degree of methacrylation (DoM). The microwave-assisted synthesis significantly reduced the reaction time from 24 h to 6 min, improved reaction efficiency, and shortened the purification period from 3 days to 1 day. Additionally, it enhanced the mechanical, rheological, and swelling properties of the resulting hydrogels. The highest DoM was achieved at 78 % for HAMA-100 hydrogels synthesized at 100 W microwave energy. Rheological analysis demonstrated that microwave-assisted HAMA hydrogels could withstand nearly 100 % strain, outperforming those produced by conventional methods. This indicated the presence of an improved energy distribution mechanism at the molecular level within the polymer network structure of the microwave-assisted hydrogels. It was also observed that the microwave-assisted hydrogels exhibited strain-hardening behavior, ensuring the stability of bioactive structures in bioinks. Furthermore, the printing conditions for HAMA-100 gels were optimized in terms of printing pressure and speed. These findings highlight the significant role of microwave energy in achieving superior hydrogel properties, making it a promising green method for preparing bioinks for 3D printing applications.
Citation - WoS: 3
Citation - Scopus: 3
HER2-Specific Peptide (LTWWYSPY) and Antibody (Herceptin) Targeted Core Cross-Linked Micelles for Breast Cancer: A Comparative Study
(MDPI, 2023) Bayram, Nazende Nur; Ulu, Gizem Tugce; Abdulhadi, Nusaibah Abdulsalam; Guerdap, Seda; Isoglu, Ismail Alper; Baran, Yusuf; Isoglu, Sevil Dincer; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
This study aims to prepare a novel breast cancer-targeted micelle-based nanocarrier, which is stable in circulation, allowing intracellular drug release, and to investigate its cytotoxicity, apoptosis, and cytostatic effects, in vitro. The shell part of the micelle is composed of zwitterionic sulfobetaine ((N-3-sulfopropyl-N,N-dimethylamonium)ethyl methacrylate), while the core part is formed by another block, consisting of AEMA (2-aminoethyl methacrylamide), DEGMA (di(ethylene glycol) methyl ether methacrylate), and a vinyl-functionalized, acid-sensitive cross-linker. Following this, a targeting agent (peptide (LTVSPWY) and antibody (Herceptin((R)))), in varying amounts, were coupled to the micelles, and they were characterized by H-1 NMR, FTIR (Fourier-transform infrared spectroscopy), Zetasizer, BCA protein assay, and fluorescence spectrophotometer. The cytotoxic, cytostatic, apoptotic, and genotoxic effects of doxorubicin-loaded micelles were investigated on SKBR-3 (human epidermal growth factor receptor 2 (HER2)-positive) and MCF10-A (HER2-negative). According to the results, peptide-carrying micelles showed a higher targeting efficiency and better cytostatic, apoptotic, and genotoxic activities than antibody-carrying and non-targeted micelles. Also, micelles masked the toxicity of naked DOX on healthy cells. In conclusion, this nanocarrier system has great potential to be used in different drug-targeting strategies, by changing targeting agents and drugs.
Citation - WoS: 12
Citation - Scopus: 12
HER2-Targeted, Degradable Core Cross-Linked Micelles for Specific and Dual pH-Sensitive Dox Release
(Wiley-VCH Verlag GmbH, 2022) Bayram, Nazende Nur; Ulu, Gizem Tugce; Topuzogullari, Murat; Baran, Yusuf; Isoglu, Sevil Dincer; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
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.
Peptide Targeted Core Cross-Linked Micelles for Dox Delivery to HER2 Expressing Cancer Cells
(Mary Ann Liebert, inc, 2022) Bayram, Nazende Nur; Ulu, Gizem Tugce; Gurdap, Seda; Isoglu, Ismail Alper; Baran, Yusuf; Isoglu, Sevil Dincer; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
Citation - WoS: 4
Citation - Scopus: 3
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; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
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.
Citation - WoS: 14
Citation - Scopus: 14
Preparation of Antibacterial Electrospun Poly(D, L-Lactide-co-Glycolide)/Gelatin Blend Membranes Containing Hypericum Capitatum Var. Capitatum
(Taylor & Francis As, 2021) Aksit, Nazende Nur; Gurdap, Seda; Isoglu, Sevil Dincer; Isoglu, Ismail Alper; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
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.
Citation - WoS: 6
Citation - Scopus: 5
Raft-Synthesized Poegma-B Block Copolymers: Preparation of Nanosized Micelles for Anticancer Drug Release
(Springer, 2022) Bayram, Nazende Nur; Topuzogullari, Murat; Isoglu, Ismail Alper; Isoglu, Sevil Dincer; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
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. [GRAPHICS] .
Citation - WoS: 12
Citation - Scopus: 12
Sulfobetaine-Based Homo- and Copolymers by Raft: Cross-Linked Micelles and Aqueous Solution Properties
(Amer Chemical Soc, 2022) Gurdap, Seda; Bayram, Nazende Nur; Isoglu, Ismail Alper; Isoglu, Sevil Dincer; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
In this study, we describe the synthesis and aqueous solution behavior of temperature-sensitive N-(3-sulfopropyl)-N-methacroyloxyethyl-N,N-dimethylammonium betaine (SBMA) homopolymers and core cross-linked micelles (CCMs) with an SBMA shell. Reversible addition- fragmentation chain transfer polymerization has been utilized to synthesize sulfobetaine homopolymers, followed by CCM formation during copoly-merization in the presence of an acid-degradable cross-linker. First, SBMA homopolymers of varying chain lengths were synthesized, and it has been demonstrated that an increase in the chain length and concentration of the homopolymer resulted in an increase in the upper critical solution temperature (UCST). Besides, micelles showed concentration-dependent dual temperature-sensitive behavior with UCST and LCST transitions. Also, homopolymers and CCMs were characterized by FTIR, H-1-NMR, GPC, and TEM. Micelle formation and temperature sensitivity were also investigated by DLS. As a result, stabilized micelles were successfully prepared with the motivation of preventing premature drug release and achieving a pH-and temperature-controlled system. Due to their dual-responsive characteristics, the CCMs show promising potential to be used as smart drug carriers for controlled delivery.
Citation - WoS: 8
Citation - Scopus: 8
Thermo-Responsive Complexes of c-Myc Antisense Oligonucleotide With Block Copolymer of Poly(OEGMA) and Quaternized Poly(4-Vinylpyridine)
(Wiley-VCH Verlag GmbH, 2017) Topuzogullari, Murat; Elalmis, Yeliz Basaran; Isoglu, Sevil Dincer; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.01. Biyomühendislik
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.