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    Development and in vitro evaluation of temozolomide-loaded PLGA nanoparticles in a thermoreversible hydrogel system for local administration in glioblastoma multiforme
    (Elsevier, 2020) Sayiner, Ozgun; Arisoy, Sema; Comoglu, Tansel; Ozbay, Feyza Gul; Esendagli, Gunes
    With its ability to cross the blood-brain barrier, temozolomide (TMZ) is the first-line treatment option in glioblastoma multiforme therapy. This study aims to design TMZ-loaded PLGA nanoparticles (TMZ-PLGA-NP) in a thermoreversible hydrogel system comprising Pluronic (R) F-127. TMZ-PLGA-NP were prepared via emulsion-solvent evaporation method using dimethylformamide (DMF) as organic solvent and PVA solution as stabilizer. Experimental parameters for the formulation process and in vitro release profiles of free drug, TMZ-PLGA-NP and TMZ-PLGA-NP-loaded in hydrogel were investigated. Particle size in the range of 100-200 nm with an encapsulation efficiency of 55-70% has been obtained. In vitro studies showed that the TMZ-PLGA-NP loaded in hydrogel formulations have significantly slowed down the release process, providing controlled and sustained release. These nanoparticles were efficiently taken up by the glioblastoma cells and the TMZ released from the TMZ-PLGA-NP-loaded in hydrogel could reach to the efficiency of direct exposure to the free-drug. In conclusion, the thermoreversible hydrogel system containing TMZ-loaded PLGA nanoparticles may serve as a promising approach that could sustain long-term drug release for the treatment of residual glial tumors after surgery.
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    Development, Evaluation, and Molecular Dynamics Study of Ampicillin-Loaded Chitosan-Hyaluronic Acid Films as a Drug Delivery System
    (Amer Chemical Soc, 2024) Arisoy, Sema; Bux, Khair; Herwig, Ralf; Salva, Emine
    Periodontitis is an inflammatory periodontal disease defined by the progressive loss of tissues surrounding the tooth. Ampicillin is an antibiotic for managing and treating specific bacterial infections, including periodontitis. Periodontal pockets occur due to periodontal disease progression and act as a natural reservoir that is easily reachable for the insertion of a delivery system, and the amount of drug to be released has a major role in the efficiency of treatment of the disease. Polyelectrolyte complexes (PECs), particularly those based on chitosan and hyaluronic acid combinations, offer a promising avenue to overcome the challenges associated with drug delivery. These complexes are both biodegradable and biocompatible, making them an optimal choice for enabling targeted drug delivery. This study centers on developing and assessing the structure and dynamic attributes of a drug-PEC system encompassing ampicillin and chitosan-hyaluronic acid components, which represents a targeted drug delivery system to better alleviate the periodontitis. To achieve this goal, we conducted experiments including weight and drug content uniformity, swelling & imath;ndex, drug release %, FT-IR and SEM analyses, and atomistic molecular dynamics simulations on the drug PECs loaded with ampicillin with varying amounts of hyaluronic acid. All simulations and the experimental analysis suggested that increased HA amount resulted in an increase in drug release % and swelling index. The simulation outcomes provide insights into the nature of the drug and PEC interactions alongside transport properties such as drug diffusion coefficients. These coefficients offer valuable insights into the molecular behavior of ampicillin-PEC drug delivery systems, particularly in the context of their application in periodontitis treatment.
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    Effect of Formulation Variables for the Production of WGA-Grafted, Levodopa-Loaded PLGA Nanoparticles
    (Trans Tech-Scitec Publications Ltd, 2021) Arisoy, Sema; Comoglu, Tansel
    Levodopa is used for the treatment of Parkinson's Disease (PD) for the last few decades. However, adverse reactions such as dyskinesia, somnolence, nausea, itching, rash, as well as the need for frequent dosing and low bioavailability problems affect the success of the treatment. To prevent side effects caused by conventional therapy, a nanoparticular drug delivery system has been developed, in which receptors are constantly stimulated, and the frequency of dosing is reduced. In this study, levodopa was loaded in Poly lactic-co-glycolic acid (PLGA) nanoparticles (NP) which modified with Wheat Germ Agglutinin (WGA) to increase the effectiveness of levodopa, reduce its side effects and apply to the nasal area which is an alternative way for brain targeting with lower doses. To obtain the optimum levodopa loaded PLGA nanoparticles, the effect of some formulation variables such as polyvinyl alcohol (PVA) concentration, homogenization speed, polymer amount and molecular weight, and levodopa content on the entrapment efficiency (EE) and particle size of the nanoparticles were investigated. Besides these variables, the effect of different parameters on the WGA binding constant was also searched. In addition to in vitro release studies, Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectrophotometer (FT-IR), and Transmission electron microscopy (TEM) analysis were used in the characterization of nanoparticles. Among all formulations, A2 and A8a which was produced with different molecular weights of PLGA, different added levodopa amounts and with different homogenization speeds were chosen as optimum formulations due to their sustained release properties and the ability to release 80 % of their drug content.WGA binding constant was found 78.20 % for A8a-1 and 95 % for A2-1. In this study, we aimed to determine the effect of different formulation parameters on the development of levodopa loaded and WGA grafted PLGA nanoparticles and on the quality characteristics of nanoparticle formulations such as particle size, zeta potential, and EE. In this paper, the results are demonstrated for a better understanding of the effect of process parameters on the development of nanoparticle-based drug delivery systems by using the double-emulsion solvent evaporation technique and on WGA binding of drug-loaded PLGA nanoparticles.
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    Evaluation of the Effect of Honey-Containing Chitosan/Hyaluronic Acid Hydrogels on Wound Healing
    (Mdpi, 2023) Salva, Emine; Akdag, Ahmet Enes; Alan, Saadet; Arisoy, Sema; Akbuga, Fatma Julide
    The 3D polymeric network structure of hydrogels imitates the extracellular matrix, thereby facilitating cell growth and differentiation. In the current study, chitosan/hyaluronic acid/honey coacervate hydrogels were produced without any chemicals or crosslinking agents and investigated for their wound-healing abilities. Chitosan/hyaluronic acid/honey hydrogels were characterized by FTIR, SEM, and rheology analysis. Moreover, their water content, water uptake capacities, and porosity were investigated. In FT-IR spectra, it was discovered that the characteristic band placement of chitosan with hyaluronic acid changed upon interacting with honey. The porosity of the honey-containing hydrogels (12%) decreased compared to those without honey (17%). Additionally, the water-uptake capacity of honey-containing hydrogels slightly decreased. Also, it was observed that hydrogels' viscosity increased with the increased hyaluronic acid amount and decreased with the amount of honey. The adhesion and proliferation of fibroblast cells on the surface of hydrogel formulations were highest in honey-containing hydrogels (144%). In in vivo studies, wound healing was accelerated by honey addition. It has been demonstrated for the first time that honey-loaded chitosan-hyaluronic acid hydrogels, prepared without the use of toxic covalent crosslinkers, have potential for use in wound healing applications.
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    In vitro and in vivo evaluation of levodopa-loaded nanoparticles for nose to brain delivery
    (Taylor & Francis Ltd, 2020) Arisoy, Sema; Sayiner, Ozgun; Comoglu, Tansel; Onal, Deniz; Atalay, Ozbeyen; Pehlivanoglu, Bilge
    Parkinson's disease (PD) is a neurodegenerative disease which is characterized by the loss of dopaminergic neurons in the brain. Levodopa is the drug of choice in the treatment of PD but it exhibits low oral bioavailability (30%) and very low brain uptake due to its extensive metabolism by aromatic amino acid decarboxylase in the peripheral circulation. Moreover, levodopa has psychic, gastrointestinal, and cardiovascular side effects, and most importantly, short and frequent stimulation of dopamine receptors lead to undesirable conditions such as dyskinesia over time. The challenges are to increase the therapeutic efficiency, the bioavailability and decreasing the unfavourable side effects of levodopa. Biocompatible nano-sized drug carriers could address these challenges at molecular level. For this purpose, levodopa-loaded Poly (lactide-co-glycolide) acid nanoparticles were prepared by double emulsion-solvent evaporation method for nose to brain drug delivery. Parameters such as homogenization speed, and external and internal phase content were modified to reach the highest loading efficiency. F1-1 coded formulation showed prolonged release up to 9 h. Carbodiimide method was used for surface modification studies of nanoparticles. The efficacy of the selected nanoparticle formulation has been demonstrated by in vivo experiments in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced PD model in mice.
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    Potential Treatment Approaches to SARS-CoV-2 and Evaluation of Drug Carrier Systems in Treatment
    (Galenos Publ House, 2020) Arisoy, Sema; Comoglu, Tansel
    The severe acute respiratory syndrome-coronaviruse-2 (SARS-CoV-2) genome is packaged in a helical nucleocapsid surrounded by a lipid bilayer. The virus envelope contains at least three viral proteins called spike protein (S), membrane protein (M) and envelope protein (E). While M and E form the structure of the virus, S protein is the leading agent of the entry of viruses into the host. Angiotensin converting enzyme-2 (ACE-2) has been identified as a functional receptor for coronaviruses, including SARS-CoV and SARS-CoV-2. Viral fusion is the main step in the onset of SARS-CoV-2 infection. It is thought that drugs that prevent spike protein and ACE-2 fusion, drugs acting on the renin-angiotensin aldesterone system, and a high dose ACE-2 can act on this fusion mechanism and take part in COVID-19 treatment. In this context, especially nano-sized liposomal carriers attract attention due to their biocompatibility and cell-like structures in the treatment of infectious diseases. There are studies in which liposomes are also used as a secondary therapeutic to support traditional anti-infective drugs. In this review, therapeutic approaches that may reduce and treat the severity of the disease by preventing ACE-2 mediated entry of viruses are discussed.
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    Preparation and in vitro characterization of curcumin loaded Chitosan-Hyaluronic acid polyelectrolyte complex based hydrogels
    (Taylor & Francis Ltd, 2023) Arisoy, Sema; Salva, Emine
    Objective: The manuscript aims to prepare and comprehensively characterize curcumin-loaded chitosan-hyaluronic acid polyelectrolyte complex (PEC) hydrogels through in vitro assessments. By elucidating the formulation process, physicochemical attributes, and drug release kinetics, the study contributes to the producing of curcumin loaded new drug delivery system.Significance: This approach shows the unique synergy of the chosen polymers with curcumin. The meticulous in vitro analysis of the hydrogels cements their novel attributes, underlining their potential as efficacious and biocompatible curcumin carriers.Methods: To configure the optimum formulation variables, viscosity, swelling ratio, porosity, in vitro release, cell viability, and migration rate were determined. In addition, FTIR and SEM analyses were also carried out to define the characteristic of formulations.Results: Release kinetic determination is essential in estimating the release behavior of formulation in the body. All formulations showed Higuchi release kinetics, indicating that drug release from the semi-solid matrix was diffusion controlled.Conclusion: As a result, in this study, a new formulation was produced based on a simple concept with acceptable quality parameter results promising to be conducted in the industry. [GRAPHICS]