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Öğe A polyphenolic biomacromolecule prepared from a flavonoid: Catechin as degradable microparticles(Wiley, 2021) Sağbaş Suner, Selin; Mohapatra, Subhra; Ayyala, Ramesh S.; Brethanabotla, Venkat R.; Şahiner, NurettinCatechin (CAT) was crosslinked with trimethylolpropane triglycidyl ether(TMPTGE) to obtain degradable poly(CAT) particles in a single step. Sphericalp(CAT) particles with tens of micrometer size range and an isoelectronic pointat pH 1.2 were obtained. The hydrolytic degradation of p(CAT) particles pro-vided sustainable and extended release with 264 mg/g CAT release within10 days at pH 7.4. The antioxidant capacity of 55.0 ± 0.9μg/ml gallic acidequivalent in terms of total phenol content, and 0.88 ± 0.3μmol/g trolox equiv-alent were estimated for p(CAT) particles displaying strong radical scavengingcapability. Blood clotting and hemolysis assays demonstrated dose-dependentblood compatibility revealing higher blood compatibility for p(CAT) particlesup to 10μg/ml concentration. The cytotoxicity results show that p(CAT) parti-cles have almost no toxicity for CCD841 normal colon cells at 250μg/ml con-centration in 24 h incubation time giving ~97% cell viability, whereas CATmolecules only provide ~34% cell viabilityÖğe Antimicrobial activity and biocompatibility of slow-release hyaluronic acid-antibiotic conjugated particles(Elsevier, 2020) Zhang, Ze; Suner, Selin S.; Blake, Diane A.; Ayyala, Ramesh S.; Şahiner, NurettinHere, the aim was to design and use a long-lasting antibiotic release system for prevention of postoperative infections in ophthalmic surgery. Ciprofloxacin and vancomycin-conjugated hyaluronic acid (HA) particles were prepared as drug carriers for sustained release of antibiotics. The antimicrobial effects of the released drugs were determined by disc-diffusion and macro-dilution tests at different times up to 2 weeks. Slow degradable HA particles were obtained with 35.2 wt% degradation within 21 days. The drug loading amount was increased by employing two sequential chemical linking (conjugation, 2C) and one physical absorption loading (A) procedures (2C + A processes) from 148 +/- 8 to 355 +/- 11 mg/g HA particles for vancomycin. The amounts of vancomycin and ciprofloxacin that were released linearly was estimated as 64.35 +/- 7.35 and 25.00 +/- 0.68 mg/g, respectively, from drug-conjugated HA particles in 100 h. Antimicrobial studies revealed that antibiotic-conjugated HA particles could inhibit the growth of microorganisms from 1 h to 1 week. The MBC values were measured as 0.25, 4.0, and 0.25 mg/mL against Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis, respectively, after 72 h incubation time. Cytotoxicity studies showed no difference between fibroblast growth or corneal thickness after 5 days with or without HA-antibiotic particles. The drug release studies and antimicrobial activity of antibiotic-loaded HA particles with time against various bacteria further revealed that HA particles are very effective in preventing bacterial infections. Likewise, cytotoxicity studies suggest that these particles pose no toxicity to eukaryotic cells, including corneal endothelium.Öğe Antipathogenic Activity of Betainized Polyethyleneimine Sprays Without Toxicity(Mdpi, 2024) Suner, Selin S.; Ayyala, Ramesh S.; Şahiner, NurettinBackground/Objectives: The design of alternative antipathogenic sprays has recently attracted much attention due to the limitations of existing formulations, such as toxicity and low and narrow efficacy. Polyethyleneimine (PEI) is a great antimicrobial polymer against a wide range of pathogens, but toxicity limits its use. Here, betainized PEI (B-PEI) was synthesized to decrease the toxicity of PEI and protonated with citric acid (CA), boric acid (BA), and HCl to improve antimicrobial activity. Methods: Cytotoxicity of the PEI-based solutions was determined on L929 fibroblast cells. Antibacterial/fungal activity of PEI-based antipathogenic sprays was investigated by microtiter and disc diffusion assays, in addition to bacterial viability and adhesion % of common bacteria and fungi on the PEI-treated masks. Furthermore, the antiviral effect of the PEI-based solutions was determined against SARS-CoV-2 virus. Results: The biosafe concentration of PEI was determined as 1 mu g/mL with 75 +/- 11% cell viability, but B-PEI and its protonated forms had great biocompatibility even at 1000 mu g/mL with more than 85% viability. The antibacterial/fungal effect of non-toxic B-PEI was improved by protonation with BA and HCl with 2.5-10 mg/mL minimum bactericidal/fungicidal concentrations (MBCs/MFCs). Bacterial/fungal viability and adhesion on the mask was almost eliminated by using 50 mu L with 5-10 mg/mL of B-PEI-BA. Both protonated bare and betainized PEI show potent antiviral activity against SARS-CoV-2 virus. Conclusions: The toxicity of PEI was overcome by using betainized forms of PEI (B-PEI). Furthermore, the antimicrobial and antiviral efficacy of PEI and B-PEI was improved by protonation with CA, BA, and HCl of amine groups on B-PEI. B-PEI-BA spray solution has great potential as an antipathogenic spray with broad-spectrum antimicrobial potency against harmful bacteria, fungi, and viruses without any toxicity.Öğe Biocompatible Glycol Chitosan Microgels as Effective Drug Carriers(MDPI, 2023) Şahiner, Mehtap; Yılmaz, Aynur Sanem; Ayyala, Ramesh S.; Şahiner, NurettinGlycol chitosan (GC) is a chitosan (CH) derivative with improved water solubility with regards to CH which affords significant solubility advantages. In this study, microgels of GC as p(GC) were synthesized by a microemulsion technique at various crosslinking ratios e.g., 5%, 10%, 50%, 75%, and 150% based on the repeating unit of GC using divinyl sulfone (DVS) as a crosslinker. The prepared p(GC) microgels were tested for blood compatibility and it was found that p(GC) microgels at 1.0 mg/mL concentration possessed a 1.15 ± 0.1% hemolysis ratio and 89 ± 5% blood clotting index value confirming their hemocompatibility. In addition, p(GC) microgels were found biocompatible with 75.5 ± 5% cell viability against L929 fibroblasts even at a 2.0 mg/mL concentration. By loading and releasing tannic acid (TA) (a polyphenolic compound with high antioxidant activity) as an active agent, p(GC) microgels’ possible drug delivery device application was examined. The TA loading amount of p(GC) microgels was determined as 323.89 mg/g, and TA releases from TA loaded microgels (TA@p(GC)) were found to be linear within 9 h and a total amount of TA released was determined as 42.56 ± 2 mg/g within 57 h. According to the Trolox equivalent antioxidant capacity (TEAC) test, 400 µL of the sample added to the ABTS+ solution inhibited 68.5 ± 1.7% of the radicals. On the other hand, the total phenol content (FC) test revealed that 2000 μg/mL of TA@p(GC) microgels resulted in 27.5 ± 9.5 mg/mL GA eq antioxidant properties.Öğe Biofilm inhibition and bacterial eradication by C-dots derived from polyethyleneimine-citric acid(Elsevier B.V., 2022) Abraham, Wakeem L.; Demirci, Şahin; Wypyski, Madison S.; Ayyala, Ramesh S.; Bhethanabotla, Venkat R.; Lawson, Louise B.; Şahiner, NurettinProtonable polyethyleneimine (PEI) and citric acid (CA) based C-dots were prepared via a hydrothermal process, yielding particles with a hydrodynamic diameter of ~100 and ~80 nm, and zeta potential of ? 2.3 ± 0.1 and + 23.4 ± 0.2 mV for PEI-CA C-dots and their protonated form, respectively. Treating Staphylococcus aureus with these C-dots resulted in a statistically significant reduction in bacterial growth, specifically growth in the planktonic phase as well as in the development of bacterial biofilm when compared to untreated (p < 0.05). When 24 h matured S. aureus biofilms were treated with C-dots, a significant disruption and dispersion of bacteria from the existing biofilms was noted as compared to untreated (p < 0.05). Other Gram-positive microorganisms (B. cereus, S. epidermidis, S. pyogenes) and Gram-negative (P. mirabilis, E. coli, and P. aeruginosa) were also susceptible to the antimicrobial activity of the PEI-CA C-dots with significant inhibition of bacterial growth noted for all organisms after C-dot treatment. Only for B. cereus, S. epidermidis, and P. aeruginosa was this reduction in total growth reflected in decreased planktonic growth. However, biofilm formation by all organisms was reduced significantly upon treatment with the C-dots, including those for which planktonic growth was not impacted. © 2022 Elsevier B.V.Öğe Carbon Tetrafluoride, Oxygen, and Air RF Plasma Modified Low-Density Polyethylene and Polydimethylsiloxane(Springer, 2023) Polat, Osman; Bhethanabotla, Venkat R.; Ayyala, Ramesh S.; Şahiner, NurettinLow-density polyethylene (LDPE) and polydimethylsiloxane (silicone or PDMS) were exposed to low-pressure air, oxygen (O2), and carbon tetrafluoride (CF4) plasma to modify their surfaces. Plasma power and irradiation time were varied to determine the optimal yield for the water contact angle (θ). For both polymers, the CF4 plasma treatment resulted in the fluorination of the surfaces corroborated by FT-IR and XPS analysis, while small changes in the corresponding θ could be observed. For the O2 and air plasma treatment, the θ values of LDPE were reduced from 100° to around 60°. The changes in surface free energies (SFE) were compared for pre- and post-plasma gas treatment for both polymers and their stability under different aging conditions e.g., air, vacuum, and in water were investigated. The SFE of silicone was increased with the O2 plasma treatment from 10 to 75 mN/m and remained stable in water. Whereas the SFE of LDPE was indifferent to all storing conditions and stable up to 168 h. Also, while the SFE for the CF4 plasma-treated silicone remained almost unchanged, for the LDPE it was decreased to 15 from 35 mN/m. The wettability studies under different conditions e.g., different pH, NaCl, and BSA concentrations affirmed that they can be potentially used for biomedical applications. Finally, the multiple successive gas plasma treatment of LDPE and silicone were done up to 6 times to attain the θ values in the desired range e.g., about 120° to 30° for LDPE and 120° to 13° for silicone.Öğe Carboxymethyl Chitosan Microgels for Sustained Delivery of Vancomycin and Long-Lasting Antibacterial Effects(Mdpi, 2023) Şahiner, Mehtap; Yilmaz, Aynur S.; Ayyala, Ramesh S.; Şahiner, NurettinCarboxymethyl chitosan (CMCh) is a unique polysaccharide with functional groups that can develop positive and negative charges due to the abundant numbers of amine and carboxylic acid groups. CMCh is widely used in different areas due to its excellent biocompatibility, biodegradability, water solubility, and chelating ability. CMCh microgels were synthesized in a microemulsion environment using divinyl sulfone (DVS) as a crosslinking agent. CMCh microgel with tailored size and zeta potential values were obtained in a single stem by crosslinking CMCh in a water-in-oil environment. The spherical microgel structure is confirmed by SEM analysis. The sizes of CMCh microgels varied from one micrometer to tens of micrometers. The isoelectric point of CMCh microgels was determined as pH 4.4. Biocompatibility of CMCh microgels was verified on L929 fibroblasts with 96.5 & PLUSMN; 1.5% cell viability at 1 mg/mL concentration. The drug-carrying abilities of CMCh microgels were evaluated by loading Vancomycin (Van) antibiotic as a model drug. Furthermore, the antibacterial activity efficiency of Van-loaded CMCh microgels (Van@CMCh) was investigated. The MIC values of the released drug from Van@CMCh microgels were found to be 68.6 and 7.95 & mu;g/mL against E. coli and S. aureus, respectively, at 24 h contact time. Disk diffusion tests confirmed that Van@CMCh microgels, especially for Gram-positive (S. aureus) bacteria, revealed long-lasting inhibitory effects on bacteria growth up to 72 h.Öğe Chemically Cross-Linked Poly(?-Cyclodextrin) Particles as Promising Drug Delivery Materials(Amer Chemical Soc, 2021) Demirci, Şahin; Khiev, Dawin; Can, Mehmet; Şahiner, Mehtap; Biswal, Manas R.; Ayyala, Ramesh S.; Şahiner, NurettinOne-pot synthesis of poly(β-cyclodextrin) (p(β-CD)) micro-/nanoparticles was accomplished using two different cross-linkers, divinyl sulfone (DVS) as p(β-CD)-1 and trimethylolpropane glycidyl ether (TMPGDE) as p(β-CD)-2. High gravimetric yields of 84 ± 4 and 62 ± 6%, respectively, were attained for p(β-CD)-1 and p(β-CD)-2 particles. The p(β-CD)-1 and p(β-CD)-2 particles had spherical shapes with 5.09 ± 0.24 and 0.60 ± 0.01 μm diameters, respectively, and exhibited good water dispersibility at physiological pH, and their isoelectric points were calculated correspondingly to be pH 1.1 and 1.2. The surface areas of p(β-CD)-1 and p(β-CD)-2 particles were determined to be 4.76 ± 0.6 and 2.18 ± 0.2 m2/g, respectively. Moreover, p(β-CD) particles were found to be biocompatible with more than 98% cell viability on human retinal pigment epithelial (ARPE-19) cells at 0.1 mg/mL concentration. Also, p(β-CD)-1 particles exhibited 52.81 ± 9.5% Fe(II) chelation capacity at 1.0 mg/mL concentration. The hemolysis and coagulation tests revealed that p(β-CD)-1 particles possessed excellent blood compatibility with a 1.18 ± 0.60% hemolysis ratio and a 92.02 ± 1.02% clotting index even at 2.0 mg/mL concentration, whereas the safety limit of p(β-CD)-2 particles for blood interactions was determined to be 0.5 mg/mL. The in vitro drug release performances of p(β-CD)-1 and p(β-CD)-2 particles for hydrophobic acyclovir and hydrophilic vancomycin model drugs at pH 7.4 PBS showed sustained releases of 2.14 ± 0.34 and 1.34 ± 0.43 mg/g acyclovir and 51.90 ± 1.09 and 61.26 ± 3.71 mg/g vancomycin within 24 h, respectively. Kinetic modeling of experimental release data revealed the best fit for drug release from p(β-CD) particles mediated by the Korsmeyer-Peppas model. ©Öğe COLL 246-Hyaluronic acid hydrogel particles with micron and nano dimensions and their applications in drug delivery(Amer Chemical Soc, 2009) Ilgin, Pinar; Ozay, Hava; Aktas, Nahit; John, Vijay T.; Blake, Diane A.; Ayyala, Ramesh S.; Şahiner, Nurettin[Anstract Not Available]Öğe Colloidal drug carries from (sub)micron hyaluronic acid hydrogel particles with tunable properties for biomedical applications(Elsevier Sci Ltd, 2010) Ilgin, Pinar; Avci, Gulden; Sılan, Coşkun; Ekici, Sema; Aktas, Nahit; Ayyala, Ramesh S.; John, Vijay T.Hyaluronic acid (HA) hydrogel particles were synthesized in a single step employing water-in-oil microemulsion system. The HA particles were formed in the micro-environments of aqueous HA solution in oil by chemical crosslinking with divinyl sulfone (DVS). To produce magnetic field responsive HA-composite particles, iron magnetic nanoparticles were introduced into microemulsion system during synthesis to obtain HA-magnetic composites. For this purpose, iron nanoparticles were separately synthesized and mixed with linear HA followed by chemical crosslinking of linear HA with DVS in the micro-environments to envelope magnetic metal nanoparticles in the emulsion system. Scanning electron microscopy (SEM), dynamic light scattering (DLS) studies, and zeta potentials measurement were performed for particle size, charge and morphological characterization. Additionally. HA particles were chemically modified to induce desired functional groups on the particle surface and utilized for potential drug delivery vehicles. Trimethoprim (TMP) a bacteriostatic antibiotic drug were used as a model drug for the release studies in phosphate buffer solution (PBS) at pH 7.4 from bare HA, magnetic HA-composite and modified HA hydrogel particles. (C) 2010 Elsevier Ltd. All rights reserved.Öğe Crosslinked poly(Lactose) microgels and nanogels for biomedical applications(Academic Press Inc Elsevier Science, 2019) Can, Mehmet; Ayyala, Ramesh S.; Şahiner, NurettinHypothesis: Lactose (LAC) is a primary carbohydrate and energy source of milk has received intensive attention due to its' unique functional and nutritional properties. Many biological beneficences of LAC make it an appealing molecule to seek for designing functional interfaces. Therefore, crosslinked poly(lactose) (p(LAC)) microgel from lactose disaccharides for potential biomedical applications was pursued as biocolloids for the first time. Experiment: p(LAC) microgels prepared by chemical crosslinking with DiVinyl Sulfone (DVS) were chemically modified with ethylenediamine (EDA) to obtain amine-modified p(LAC) (p(LAC)-EDA) microgels to induce new functionalities and properties. Blood compatibilities of bare p(LAC)-EDA microgels were tested through hemolysis and blood clotting tests. Rosmarinic acid (RA) used as a model drug was loaded into p(LAC) and p(LAC)-EDA microgels to demonstrate their applicability to be used in drug loading and release applications. Findings: A facile preparation of p(LAC) microgels with high yield, 90 +/- 5% and 0.5-50 mu m size range was accomplished via water-in-oil (w/o) microemulsion crosslinking method. Upon chemical modification, the isoelectric point (IEP) from pH 1.8 for p(LAC) microgels changed to pH 7.7 for p(LAC)-EDA microgels, and the blood compatibility studies revealed that both microgels can be considered as blood compatible up to 2 mg/mL concentration, and only slight decrease in blood clotting index (BCI) of p(LAC)-EDA microgels was observed. Rosmarinic Acid (RA) was demonstrated to be released up to 4 days in phosphate buffer saline (PBS) with a linear release profile for p(LAC)-EDA microgels. (C) 2019 Elsevier Inc. All rights reserved.Öğe Cryogel composites based on hyaluronic acid and halloysite nanotubes as scaffold for tissue engineering(Elsevier Science Bv, 2019) Suner, Selin S.; Demirci, Şahin; Yetiskin, Berkant; Fakhrullin, Rawil; Naumenko, Ekaterina; Okay, Oguz; Ayyala, Ramesh S.We present here preparation of mechanically strong and biocompatible cryogel composites based on hyaluronic acid (HA) and halloysite nanotubes (HNTs) of various compositions, and their applications as scaffold for different cell growing media. Uniaxial compression tests reveal that the incorporation of HNTs into HA cryogels leads to a similar to 2.5-fold increase in their Young moduli, e.g., from 38 +/- 1 to 99 +/- 4 kPa at a HA:HNTs weight ratio of 1:2. Although HA:HNTs based cryogels were found to be blood compatible with 1.37 +/- 0.11% hemolysis ratio at a HA:HNTs weight ratio of 1:2, they trigger thrombogenic activity with a blood clotting index of 17.3 +/- 4.8. Remarkably, HA:HNTs cryogel composites were found to be excellent scaffold materials in the proliferation of rat mesenchymal stem cells (MSC), human cervical carcinoma cells (HeLa), and human colon cancer cells (HCT116). The cell studies revealed that an increased amount of HNT embedding into HA cryogels leads to an increase of MSC proliferation. (C) Elsevier B.V. All rights reserved.Öğe Degradable and Non-Degradable Chondroitin Sulfate Particles with the Controlled Antibiotic Release for Bacterial Infections(Mdpi, 2022) Sağbaş Suner, Selin; Şahiner, Mehtap; Ayyala, Ramesh S.; Şahiner, NurettinNon-degradable, slightly degradable, and completely degradable micro/nanoparticles derived from chondroitin sulfate (CS) were synthesized through crosslinking reactions at 50%, 40%, and 20% mole ratios, respectively. The CS particles with a 20% crosslinking ratio show total degradation within 48 h, whereas 50% CS particles were highly stable for up to 240 h with only 7.0 +/- 2.8% weight loss in physiological conditions (pH 7.4, 37 degrees C). Tobramycin and amikacin antibiotics were encapsulated into non-degradable CS particles with high loading at 250 g/mg for the treatment of corneal bacterial ulcers. The highest release capacity of 92 +/- 2% was obtained for CS-Amikacin particles with sustainable and long-term release profiles. The antibacterial effects of CS particles loaded with 2.5 mg of antibiotic continued to render a prolonged release time of 240 h with 24 +/- 2 mm inhibition zones against Pseudomonas aeruginosa. Furthermore, as a carrier, CS particles significantly improved the compatibility of the antibiotics even at high particle concentrations of 1000 g/mL with a minimum of 71 +/- 7% fibroblast cell viability. In summary, the sustainable delivery of antibiotics and long-term treatment of bacterial keratitis were shown to be afforded by the design of tunable degradation ability of CS particles with improved biocompatibility for the encapsulated drugs.Öğe Degradable poly(catechin) nanoparticles as a versatile therapeutic agent(Taylor and Francis Ltd., 2021) Suner, Selin S.; Şahiner, Mehtap; Mohapatra, Subhra; Ayyala, Ramesh S.; Bhethanabotla, Venkat R.; Şahiner, NurettinPoly(catechin) (p(CAT)) nanoparticles (NPs), 173 +/- 4 nm was prepared as a therapeutic agent with hydrolytic degradability affording sustainable CAT release over 20 d at carcinogenic conditions, pH 5.5 and 37.5 degrees C. Cell viability studies on MC38 colon cancer cells revealed the anticancer potential of p(CAT) NPs with 691 mu g/mL IC50 value while being well-tolerated by nonmalignant CCD841 CoN colon cells at 72 h incubation-time. P(CAT) NPs showed effective antioxidant capacity with 241 +/- 7 and 456 +/- 54 mu g/mL of GA equivalency of total phenol content (TPC), and total flavonoid content (TFC) values and 1.19 +/- 0.8 mu mol/g Trolox equivalent antioxidant capacity by 2,2'-Azino-bis-(3-ethylbenzothioazoline-6-sulfonic acid (ABTS(center dot+)) scavenging assay.Öğe ESI-IM-MS characterization of cyclodextrin complexes and their chemically cross-linked alpha (?-), beta (?-) and gamma (?-) cyclodextrin particles as promising drug delivery materials with improved bioavailability(Elsevier, 2023) Yilmaz, Aynur Sanem; Ozturk, Serhat; Salih, Bekir; Ayyala, Ramesh S.; Şahiner, NurettinCyclodextrins (CDs) are natural cyclic oligosaccharides with a relatively hydrophobic cavity and a hydrophilic outer surface. In this study, alpha (alpha-), beta (beta-) and gamma (gamma-) CD particles were prepared by directly using alpha-, beta-, and gamma-CDs as monomeric units and divinyl sulfone (DVS) as a crosslinker in a single-step via reverse micelle microemulsion crosslinking technique. Particles of p(alpha-CD), p(beta-CD), and p(gamma-CD) were perfectly spherical in sub 10 mu m size ranges. The prepared p(CD) particles at 1.0 mg/mL concentrations were found biocompatible with > 95 % cell viability against L929 fibroblasts. Furthermore, p(alpha-CD) and p(beta-CD) particles were found non-hemolytic with < 2 % hemolysis ratios, whereas p(gamma-CD) particles were found to be slightly hemolytic with its 2.1 +/- 0.4 % hemolysis ratio at 1.0 mg/mL concentration. Furthermore, a toxic compound, Bisphenol A (BPA) and a highly antioxidant polyphenol, curcumin (CUR) complexation with alpha-, beta-, and gamma-CD molecules was investigated via Electrospray-Ion Mobility-Mass Spectrometry (ESI-IM-MS) and tandem mass spectrometry (MS/MS) analysis. It was determined that the most stable noncovalent complex was in the case of beta-CD, but the complex stoichiometry was changed by the hydrophobic nature of the guest molecules. In addition, BPA and CUR were separately loaded into prepared p(CD) particles as active agents. The drug loading and release studies showed that p (CD) particles possess governable loading and releasing profiles.Öğe Fungal Keratitis Treatment Using Drug-Loaded Hyaluronic Acid Microgels(Amer Chemical Soc, 2022) Ayyala, Ramesh S.; Sağbaş Suner, Selin; Bhethanabotla, Venkat R.; Şahiner, Nurettinmicrogels using conjugation and encapsulation drug-loading techniques were utilized in the treatment of fungal keratitis. Natamycin (NAT) and amphotericin B (AMB) drugs were chemically linked to HA microgels by employing a chemical coupling agent to obtain conjugated (C-) HA:NAT and HA:AMB microgels. Also, these drugs were loaded into the HA microgel network during HA microgel preparation to attain encapsulated (E-) HA:NAT and HA:AMB microgels. The conjugation of drug molecules was confirmed by FT-IR spectra of bare and drugloaded HA microgels. It was determined that the AMB loading amount was about 4-fold higher for E-HA:AMB in comparison to C-HA:AMB microgels. Furthermore, the antifungal activity of drug conjugated and encapsulated HA:NAT and HA:AMB microgels was tested on Fusarium sp. and compared with the effect of bare drug molecules as control for up to 15 days of incubation time by means of the disc diffusion technique. The antifungal activity of 200 mu L at 20 mg/mL concentration of C-HA:NAT and C-HA:AMB microgels was not found to effectively inhibit Fusarium sp. growth after 1 day of incubation, whereas the same concentration of E-HA:NAT and E-HA:AMB microgels totally killed Fusarium sp. for up to 15 days. These E-HA:NAT and E-HA:AMB microgels show no cytotoxicity on the L929 fibroblast cells up to 1000 mu g/ mL concentration, whereas the free drug molecules destroy the cells even at 100 mu g/mL concentration.Öğe HA particles as resourceful cancer, steroidal and antibiotic drug delivery device with sustainable and multiple drug release capability(Taylor & Francis Group, LLC, 2021) Şahiner, Nurettin; Suner, Selin S.; Kurt, Saliha B.; Can, Mehmet; Ayyala, Ramesh S.Hyaluronic acid (HA) particles with divinyl sulfone (DVS) crosslinking at 10% mole ratio (HA macromolecule repeating units) were prepared and demonstrated as versatile drug carriers with sustainable and long-term release capabilities for cancer drugs, corticosteroid, and antibiotics. Two different methods were chosen in drug loading process; encapsulation for cancer drugs, 5-fluorouracil (5FU), mitomycin C (MMC), and doxorubicin (Dox), and dual drug conjugation for anti-inflammatory glucocorticoid dexamethasone (Dex) and antibiotic ciprofloxacin (Cipro) drugs, respectively. It was demonstrated that HA particles prepared during drug encapsulation were attained smaller sizes with 833 ± 46, 867 ± 50, 728 ± 41 nm for 5FU, MMC, and Dox, respectively. Bare and drug loaded HA particles were shown to be blood compatible with the highest hemolytic ratio of 3.1 ± 0.12% for HA-Dex-Cipro conjugates and fairly good blood clotting index with minimum 71.7 ± 6.0% for MMC encapsulated HA particles. Drug release studies from HA particles indicated that depending on the types of cancer drugs, it is possible to gradually release the drug in long-term up to 300 h in linear fashions with the highest release of 9.34 ± 2.25 mg/g for 5FU. Similarly, drug conjugated HA-Dex-Cipro particles were also showed linear dual drug release up to 100 h at physiological conditions, pH 7.4 and 37.5 °C.Öğe Hyaluronic acid (HA)-Gd(III) and HA-Fe(III) microgels as MRI contrast enhancing agents(Elsevier Ltd, 2022) Şahiner, Nurettin; Umut, Evrim; Sağbaş Suner, Selin; Şahiner, Mehtap; Culha, Mustafa; Ayyala, Ramesh S.Hyaluronic acid (HA) was crosslinked with Gd(III) and Fe(III) ions rendering physically crosslinked HA-metal(III) microgels as magnetic resonance imaging (MRI) enhancing contrast agents. These HA-Gd(III) and HA-Fe(III) microgels are injectable with size range, 50–5000 nm in water. The same isoelectric point, pH 1.2 ± 0.1, was measured for both microgels. HA-Gd(III) and HA-Fe(III) microgels are hemo-compatible biomaterials and can be safely used in intravascular applications up to 1000 μg/mL concentration. Furthermore, no significant toxicity was attained as 95 ± 8 and 81 ± 2% cell viability on L929 fibroblast cells at 100 μg/mL of HA-Gd(III) and HA-Fe(III) microgels were measured. Moreover, HA-Gd(III) microgels were found to afford significant contrast improvement capability in MRI with proton relaxivity, r1 = 2.11 mM−1 s−1, comparable with the values reported for Gd(III) labeled functionalized HA gel systems and commercial Gd based contrast agents.Öğe Light-Activated Modified Arginine Carbon Dots as Antibacterial Particles(Mdpi, 2022) Sağbaş Suner, Selin; Şahiner, Mehtap; Yılmaz, Aynur Sanem; Ayyala, Ramesh S.; Şahiner, NurettinNitrogen-doped arginine carbon dots (Arg CDs) as light-sensitive antibacterial agents were prepared by using citric acid as the carbon source and arginine amino acid as the nitrogen source via a microwave-assisted synthesis method. Dynamic light scattering (DLS) measurements and TEM images revealed that the Arg CDs were in the 1-10 nm size range with a graphitic structure. To improve their antibacterial capability, the Arg CDs were modified with ethyleneimine (EDA), pentaethylenehexamine (PEHA), and polyethyleneimine (PEI) as different amine sources, and the zeta potential value of +2.8 +/- 0.6 mV for Arg CDs was increased to +34.4 +/- 4.1 mV for PEI-modified Arg CDs. The fluorescence intensity of the Arg CDs was significantly enhanced after the modification with EDA, and the highest antibacterial effect was observed for the PEI-modified Arg CDs. Furthermore, the photodynamic antibacterial capacity of bare and EDA-modified Arg CDs was determined upon light exposure to show their light-induced antibacterial effects. Photoexcited (315-400 nm, UVA, 300 W), EDA-modified Arg CDs at 5 mg/mL concentration were found to inhibit about 49 +/- 7% of pathogenic bacteria, e.g., Escherichia coli, with 5 min of light exposure. Furthermore, the biocompatibilities of the bare and modified Arg CDs were also investigated with blood compatibility tests via hemolysis and blood clotting assays and cytotoxicity analysis on L929 fibroblast cells.Öğe Low-pressure plasma treated polycarbonate and polymethyl methacrylate (PMMA) sheets with different surface patterns to change their surface properties(Elsevier B.V., 2023) Gizer, S. Görkem; Bhethanabotla, Venkat R.; Ayyala, Ramesh S.; Şahiner, NurettinLow-pressure plasmas of carbon tetrafluoride (CF4), oxygen (O2), and air were used to treat the surfaces of polycarbonate (PC) and polymethyl methacrylate (PMMA) to achieve a variety of surface attributes, such as hydrophilicity, hydrophobicity, and surface free energy. Patterns of straight line, triangular and square shapes with different sizes e.g., 0.5 mm, 0.75 mm, and 1 mm dimensions as templates were constructed from stainless-steel sheets with a thickness of 1 mm, via laser cutter, were used to induce the corresponding shape of the functionality on PC and PMMA surfaces during plasma gas treatment were also investigated. The untreated PC and PMMA surfaces have a contact angle (θ) value of 70°±0.47° and 77°±0.80°, respectively. As expected upon CF4 plasma treatment, their contact angle values were increased to 109.04°±0.35° and 105.76°±0.61°, respectively; whereas the air plasma treated surfaces became more hydrophilic with the contact angle values of 29.34°±0.14° and 43.99°±0.22°, correspondingly. Moreover, O2 plasma treated surfaces became more hydrophilic with the contact angle values of 25.32°±0.77° for PC and 39.94°±2.05° for PMMA. Also, surface free energy (SFE) values were decreased to 11±0.87 mN/m from 41.16±0.42 mN/m for PC and to 12.11±1.53 mN/m from 35.93±1.12 mN/m for PMMA upon CF4 treated surfaces. Furthermore, SFE values were increased to 57.59±1.12 and 62.13±1.15 mN/m for PC and PMMA after air plasma treatment. PC surface's, advancing and receding contact angles were determined as 101.48°±0.33° and 65.60°±0.11° respectively for 34.77°±0.50° slide-off angles. Moreover, the advancing and receding contact angles for PMMA were found as 93°±0.64° and 61.60°±1.19°, respectively with a sliding angle of 24.49°±1.14°. X-ray Photoelectron Spectroscopy (XPS) analysis results confirmed the fluorination and oxidation of both PC and PMMA after CF4 and O2 plasma treatments, individually. PC and PMMA surfaces were treated multiple times with CF4 and Air, Air and CF4, O2 and CF4, and CF4 and O2 plasmas in succession. After multiple treatment, PC and PMMA surfaces contact angle values were decreased as low as 10.62°±0.88° and 14.96°±0.2°, respectively.