Yazar "Ozturk, Naile" seçeneğine göre listele
Listeleniyor 1 - 19 / 19
Sayfa Başına Sonuç
Sıralama seçenekleri
Öğe Comparison of Dissolution Profiles of Commercially Available Lamivudine Tablets(Dissolution Technologies, Inc, 2015) Ozturk, Naile; Kaynak, Mustafa Sinan; Sahin, SelmaThe aim of this study was to investigate the influence of dissolution medium on the in vitro release of lamivudine (100 mg) from four commercially available lamivudine tablets (one reference and three generic). Three different buffer solutions (pH 1.2, 4.5, 6.8) and deaerated water were used as the dissolution media (900 mL), and the paddle rotation speed was kept at 50 rpm with twelve replicates. An RP HPLC method was developed for analysis of lamivudine in samples obtained from dissolution studies. The mobile phase consisted of acetonitrile/water (10:90) pH adjusted to pH 2.5 with o-phosphoric acid, a C-18 column (Ace 250 x 4.60 mm, 5 mu m) was used, and the flow rate was set at 1 mL/min. All the drugs tested were very rapidly dissolving (more than 85% of the labeled amount in 15 min), and the dissolution profiles of the generic tablets were thus considered similar to that of the reference tablet in each of the buffers at pH 1.2, 4.5, and 6.8, and deaerated water. Because of the dissolution results and the high solubility and borderline permeability, a biowaiver can be proposed for lamivudine immediate-release solid oral dosage forms provided that the excipient composition of the test product is the same as or similar to that of the reference product and the excipients that have an effect on bioavailability are qualitatively and quantitatively the same as that of the reference product.Öğe Design of ocular drug delivery platforms and in vitro - in vivo evaluation of riboflavin to the cornea by non-interventional (epi-on) technique for keratoconus treatment(Elsevier, 2020) Aytekin, Eren; Ozturk, Naile; Vurla, Imran; Polat, H. Kerem; Cakmak, Hasan Basri; Calis, Sema; Pehlivan, Sibel BozdagAim: Keratoconus is a common and progressive eye disease characterized by thinning and tapering of the cornea. This degenerative eye disease is currently treated in the clinic with an interventional technique (epi-off) that can cause serious side effects as a result of the surgical procedure. The aim of this project is to design innovative formulations for the development of a riboflavin-containing medicinal product to develop a non-invasive (epi-on) keratoconus treatment as an alternative to current treatment modalities. Methods: Nanostructured lipid carriers (NLCs) were successfully loaded with either riboflavin base of riboflavin-5-phosphate sodium and designed with either Stearylamine (positive charge) or Trancutol P (permeation enhancer). In vitro characterization studies, cytotoxicity and permeability studies were performed. Selected formulations and commercial preparations were applied and compared in ex-vivo corneal drug accumulation and transition studies. Furthermore, in vivo studies were performed to assess drug accumulation in the rat cornea and the corneal stability after NLC treatment was investigated via a biomechanical study on isolated rabbit corneas. Results: Both in vitro and ex-vivo as well as in vivo data showed that from the prepared NLC formulations, the most effective formulation was riboflavin-5-phosphate sodium containing NLC with Transcutol P as permeation enhancer. It possessed the highest drug loading content, low accumulation in the cornea but high permeability through the cornea as well as the highest functional performance in corneal crosslinking. Conclusion: Topical application of riboflavin-5-phosphate sodium loaded NLC systems designed with permeation enhancer Transcutol P may act as a potential alternative for non-invasive keratoconus treatments.Öğe Development of besifloxacin HCl loaded nanofibrous ocular inserts for the treatment of bacterial keratitis: In vitro, ex vivo and in vivo evaluation(Elsevier, 2020) Polat, H. Kerem; Pehlivan, Sibel Bozdag; Ozkul, Ceren; Calamak, Semih; Ozturk, Naile; Aytekin, Eren; Firat, AysegulNovel drug delivery systems have emerged to treat bacterial keratitis, an acute infection of the cornea. In this study, besifloxacin HCl loaded insert formulations were designed and investigated in vitro, ex vivo and in vivo for the treatment of bacterial keratitis. Besifloxacin HCl (BH) or BH-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) complex containing poly(caprolactone)/polyethylene glycol (PLC/PEG) fibrous inserts were prepared with an electrospinning method. These fibrous inserts were coated with mucoadhesive polymers such as sodium alginate (SA) or thiolated sodium alginate (TSA). Developed inserts compared to commercially available drug and it was found that coating of the insert surfaces with SA and TSA, increases bioadhesion of the formulations. Insert formulations showed a burst release in the first 2 days followed by a slow-release profile. Ex vivo transport studies showed that HP-beta-CD possessed a drug delivery level close to the commercial drug. Both TSA coated inserts as well as inserts containing HP-beta-CD-drug complex were effectively reducing bacterial keratitis in rabbit eyes upon single-dose application compared to multiple dosing with the commercial drug. Consequently, TSA coated inserts as well as the inserts containing HP-beta-CD-drug complex, may be potential alternatives to conventional market product by reducing the application frequency in the clinic leading to increased patient compliance.Öğe Development of phytase targeted PLGA nanoparticles loaded with albendazole sulfoxide and praziquantel and evaluation of efficacy on the hydatid cysts(Elsevier, 2025) Gultekin, Yakup; Korkmaz, Cagla; Ozturk, Naile; Filazi, Ayhan; Deniz, Ahmet; Vural, ImranCystic echinococcosis is the metacestode stage of Echinococcus granulosus and is a worldwide public health problem. Today, various difficulties in the treatment of cystic echinococcosis limit the treatment of cystic echinococcosis. In this study, the in vitro activity of PLGA nanoparticles loaded with albendazole sulfoxide and praziquantel and targeted with phytase enzyme on Echinococcus granulosus micro-hydatid cysts was evaluated as a new formulation. For this purpose, first conjugation of PLGA polymer and phytase enzyme was performed, then albendazole sulfoxide and praziquantel loaded nanoparticles were prepared using PLGA-phytase polymer and characterization studies were performed. Permeability and cytotoxicity tests were carried out with cell culture studies of the formulations for which characterization studies were performed and it was found that the formulations did not show any cytotoxic effect. In order to evaluate the formulations, micro-hydatid cysts were developed in vitro with Echinococcus granulosus protoscoleces collected from slaughterhouse animals and the formulations were applied. In vitro hydatid cyst viability studies, approximately 50 % of cysts died on day 4 in the group applied with the combination of 10 mu g/mL free albendazole sulfoxide and 50 mu g/mL free praziquantel, while 100% of cysts died in the group applied with the new formulation containing the same amount of drug. In addition, ex vivo studies on the laminar layer of hydatid cysts obtained from sheep liver showed that the new formulation binds to the laminar layer and increases the permeability of albendazole sulfoxide and praziquantel across the laminar layer by approximately 2-fold.Öğe Discovery of new azoles with potent activity against Candida spp. and Candida albicans biofilms through virtual screening(Elsevier France-Editions Scientifiques Medicales Elsevier, 2019) Sari, Suat; Kart, Didem; Ozturk, Naile; Kaynak, F. Betul; Gencel, Melis; Taskor, Gulce; Karakurt, ArzuSystemic candidiasis is a rampant bloodstream infection of Candida spp. and C. albicans is the major pathogen isolated from infected humans. Azoles, the most common class of antifungals which suffer from increasing resistance, and especially intrinsically resistant non-albicans Candida (NAC) species, act by inhibiting fungal lanosterol 14 alpha-demethylase (CYP51). In this study we identified a number of azole compounds in 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanol/ethanone oxime ester structure through virtual screening using consensus scoring approach, synthesized and tested them for their antifungal properties. We reached several hits with potent activity against azole-susceptible and azoleresistant Candida spp. as well as biofilms of C albicans. 5i's minimum inhibitor concentration (MIC) was 0.125 mu g/ml against C. albicans, 0.5 mu g/ml against C. krusei and 1 mu g/ml against azole-resistant C. tropicalis isolate. Considering the MIC values of fluconazole against these fungi (0.5, 32 and 512 mu g/ml, respectively), 5i emerged as a highly potent derivative. The minimum biofilm inhibitor concentration (MBIC) of 5c, 5j, and 5p were 0.5 mu g/ml (and 5i was 2 mu g/ml) against C. albicans biofilms, lower than that of amphotericin B (4 mu g/ml), a first-line antifungal with antibiofilm activity. In addition, the active compounds showed neglectable toxicity to human monocytic cell line. We further analyzed the docking poses of the active compounds in C. albicans CYP51 (CACYP51) homology model catalytic site and identified molecular interactions in agreement with those of known azoles with fungal CYP51s and mutagenesis studies of CACYP51. We observed the stability of CACYP51 in complex with 5i in molecular dynamics simulations. (C) 2019 Elsevier Masson SAS. All rights reserved.Öğe Discovery of new azoles with potent activity against Candida spp. and Candida albicans biofilms through virtual screening (vol 179, pg 634, 2019)(Elsevier France-Editions Scientifiques Medicales Elsevier, 2020) Sari, Suat; Kart, Didem; Ozturk, Naile; Kaynak, F. Betul; Gencel, Melis; Taskor, Gulce; Karakurt, Arzu[Abstract Not Available]Öğe Effect of precipitation inhibitors on supersaturation and solubility of furosemide(Marmara Univ, 2021) Gulsun, Tugba; Ozturk, Naile; Kara, Asli; Sahin, Selma; Vural, ImranFurosemide is a widely used diuretic drug for the treatment of edema associated with heart, liver cirrhosis, renal diseases and hypertension. It is a Class IV drug with low aqueous solubility and low permeability according to Biopharmaceutics Classification System (BCS). Furosemide was chosen as a model drug to examine the effect of polymeric precipitation inhibitors (PPIs) on the supersaturation and solubility. Solubility and concentration change of furosemide as a function of time at pH 1.2 and 6.8 were determined to show the effects of PPIs on furosemide solubility. The 24 h equilibrium solubility of furosemide was 0.017 +/- 0.004 and 3.62 +/- 0.201 mg/mL at pH 1.2 and pH 6.8 buffer solutions, respectively. PPI type and concentration (0.05%, 0.25%) did not increase furosemide solubility at pH 1.2. However, both hydroxypropylmethylcellulose (HPMC) and polyvinylpyrrolidoneK17 (PVPK17) at two concentrations increased furosemide solubility at pH 1.2 and 6.8. In addition, viscosity of solutions was in the range of 2.2-3.7 centipoise, and it was not influenced by PPIs concentrations. Our results showed that designing supersaturated formulations using PPIs can be useful and promising to enhance solubility of furosemide.Öğe Evaluation of Antitumor Activity of a Non-Steroidal Anti-Inflammatory Drug, Ibuprofen, by a Targeted Nanoparticulate System(Colegio Farmaceuticos Provincia De Buenos Aires, 2017) Ozturk, Naile; Kara, Asli; Vural, ImranIn this study we aimed to develop a new targeted nanoparticulate system to obtain site specific delivery of ibuprofen and to determine its antitumor efficiency. The potential effect of ibuprofen as an antitumor agent was investigated on breast cancer cells based on a targeted delivery system. Ibuprofen was encapsulated to poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA nanoparticles were fabricated by nanoprecipitation method and optimized in terms of certain parameters. Then, 520C9 monoclonal antibody (mAb) was chemically conjugated to carboxylic acid end group of PLGA nanoparticles (NPs) that specifically targeted human breast adenocarcinoma cell line (MCF-7), NP-mAb combined Ibuprofen encapsulated formulations were evaluated on characterization of particle size, encapsulation efficiency, drug loading capacity, and antitumor activity. The results demonstrated that optimized Ibuprofen loaded PLGA nanoparticles prepared by nanoprecipitation technique had an ideal particle size and polydispersity index. The encapsulation efficiency of optimized nanoparticles was relatively high, 92.9 +/- 9.0 %. Also, this system had significantly reduced the cell viability on MCF-7 cell line when compared with free ibuprofen solution at the same concentration. Above all, antibody-conjugated nanoparticles showed lower cell viability (12%) than the non-targeted system. Results indicated that ibuprofen-loaded nanoparticles had significant antitumor activity on MCF-7 cells even at relatively low concentrations. mAb conjugated drug-loaded nanoparticles were successfully fabricated and this system might be a promising approach for delivery of ibuprofen in treatment of breast cancer.Öğe Evaluation of Caco-2 cell permeability of ritonavir nanosuspensions(Istanbul Univ, Fac Pharmacy, 2020) Karakucuk, Alptug; Ozturk, Naile; Celebi, NevinBackground and Aims: Poor aqueous solubility limits drug absorption through intestinal mucosa. Nanosuspensions with nanometer range particle size provides enhanced aqueous solubility and hence permeability. The objective of this study was to investigate the cytotoxicity and in vitro cell permeability through human adenocarcinoma (Caco-2) cells of ritonavir (RTV) nanosuspensions. Methods: The Microfluidization method was used to prepare nanosuspensions. Particle size (PS), polydispersity index (PI) and zeta potential (ZP) values were measured as characterization. MTT test was applied to evaluate the cytotoxic effect. Caco-2 cell lines were used for transport studies with RTV coarse powder, physical mixtures and nanosuspension. Results: Approximately 600 nm PS, 0.4 PDI and 22 mV ZP values were observed for nanosuspensions. The sample groups showed no cytotoxicity on the cell lines in any RTV concentration. However, significant cytotoxic effect was determined in groups with high amounts of sodium dodecyl sulfate. The transported RN in nanosuspension formulation enhanced by 5.3-fold and 1.5-fold in comparison with RTV coarse powder and physical mixture, respectively. Rate of the transportation and also the amount of the transported RTV were improved with nanosuspension formulation. Conclusion: Particle size reduction of RTV into nanometer size and preparing nanosuspension system was found effective to obtain enhanced cell permeability.Öğe Evaluation of Dual Effect of Sodium Borohydride (NaBH4) as a Reducing and Crosslinking Agent for Development of Novel Silver Nanoparticles (AgNPs) Loaded Chitosan-Poly (Vinyl Alcohol) (CS-PVA) Hydrogels for Wound Healing Activity(Springer, 2026) Kara, Asli; Ozturk, Naile; Gultekin, Yakup; Demir, Sevda; Sahin, Fikrettin; Vural, ImranPurpose Hydrogels are three-dimensional, crosslinked polymeric systems with high hydrophilicity and biocompatibility, making them ideal materials for wound healing applications. In this study, a silver nanoparticle (AgNP)-loaded chitosan-poly (vinyl alcohol) (CS-PVA) hydrogel was developed using a novel, simple, and cost-effective approach. In this approach, sodium borohydride (NaBH4) simultaneously acts as a reducing agent for AgNP synthesis and as a physical crosslinking agent for hydrogel formation. Methods AgNPs were synthesized via NaBH4-mediated reduction and characterized by dynamic light scattering and UV-Vis spectroscopy. The resulting hydrogels were evaluated by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy-dispersive X-ray (EDS) spectroscopy, swelling, porosity and mechanical test. In vitro biocompatibility and wound healing potential were assessed using cell viability assays and a scratch wound assay. Results Among all formulations, M30, an AgNP-loaded CS-PVA hydrogel, prepared with medium molecular weight (MMW) chitosan and 30 mL of AgNP suspension, had the best overall performance with the highest swelling degree, favorable mechanical performance. It maintained cell viability above 80% at 24 and 48 h, and showed the greatest wound closure rate, even at low AgNP concentration. Conclusion The results demonstrate that AgNP-loaded CS-PVA hydrogels prepared using NaBH4 as a dual-function agent exhibit promising biocompatibility and wound healing potential even at low AgNP content. To the best of our knowledge, this study is the first to demonstrate the dual functionality of NaBH4 in a single-step approach as both a reducing and physical crosslinking agent, providing a simple and promising strategy for the development of next-generation wound dressing materials without need for additional chemical crosslinkers.Öğe Exploiting ionisable nature of PEtOx-co-PEI to prepare pH sensitive, doxorubicin-loaded micelles(Taylor & Francis Ltd, 2020) Ozturk, Naile; Kara, Asli; Gulyuz, Sevgi; Ozkose, Umut Ugur; Tasdelen, Mehmet Atilla; Bozkir, Asuman; Yilmaz, OzgurAims This study was conducted to evaluate block copolymers containing two different poly(ethyleneimine) (PEI) amounts, as new pH-sensitive micellar delivery systems for doxorubicin. Methods Micelles were prepared with block copolymers consisting of poly(2-ethyl-2-oxazoline)-co-poly(ethyleneimine) (PEtOx-co-PEI) and poly(epsilon-caprolactone) (PCL) as hydrophilic and hydrophobic blocks, respectively. Doxorubicin loading, micelle size, pH-dependent drug release, and in vitro cytotoxicity on MCF-7 cells were investigated. Results The average size of drug-loaded micelles was under 100 nm and drug loading was between 10.7% and 48.3% (w/w). pH-sensitive drug release was more pronounced (84.7% and 68.9% (w/w) of drug was released at pH 5.0 and pH 7.4, respectively) for the micelles of the copolymer with the lowest PEI amount. The cell viability of doxorubicin-loaded micelles which were prepared by the copolymer with the lowest PEI amount was 28-33% at 72 h. Conclusions PEtOx-co-PEI-b-PCL micelles of this copolymer were found to be stable and effective pH-sensitive nano-sized carriers for doxorubicin delivery.Öğe Formulation and In Vitro Evaluation of Telmisartan Nanoparticles Prepared by Emulsion-Solvent Evaporation Technique(Turkish Pharmacists Assoc, 2020) Ozturk, Naile; Kara, Asli; Vural, ImranObjectives: Telmisartan (TLM) is an antihypertensive drug that has been shown to have antiproliferative effects on cancer cells. It has low solubility and suboptimal oral bioavailability. To investigate the potential anticancer effect of TLM on breast cancer cells, poly (D, L-lactide) (PLA) nanoparticles were formulated with the benefit of improving its solubility. Materials and Methods: TLM-loaded PLA nanoparticles were prepared by emulsion solvent evaporation. The effects of sonication time and polymer:drug ratio on nanoparticle size and drug encapsulation were investigated. TLM-loaded nanoparticles were tested against MCF-7 and MDA-MB-231 breast cancer cell lines for antiproliferative effects. Results: Nanoparticles with mean particle size 272 nm and 79% encapsulation efficiency were obtained. Sustained release TLM nanoparticles (40% in 24 h) decreased cell viability to 45% for MCF-7 cells at 72 h, even at the lowest TLM concentration, indicating better anticancer efficiency than TLM solution. Conclusion: TLM nanoparticles could be potential anticancer agents for breast cancer and deserve further studies.Öğe In Vitro Caco-2 Cell Permeability Studies of Ziprasidone Hydrochloride Monohydrate Nanocrystals(Turkish Pharmacists Assoc, 2021) Karakucuk, Alptug; Tashan, Emine; Ozturk, Naile; Celebi, NevinObjectives: The current study focused on the evaluation of the cytotoxic effect and permeability of ziprasidone hydrochloride monohydrate (ZHM) nanocrystals on Caco-2 cells. Materials and Methods: ZHM nanocrystals were prepared by the microfluidization method in the presence of polyvinylpyrrolidone as a stabilizer. Particle size (PS), particle size distribution (PDI), and zeta potential (ZP) values were measured in characterization studies. In vitro cytotoxic effects of ZHM nanocrystals were investigated using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Caco-2 transport studies were conducted with formulations of ZHM coarse powder and nanocrystals. Results: Nanocrystals were obtained with 400-600 nm PS, 0.1-0.4 PDI, and >20 mV ZP values. The cell viability remained 100% for all sample groups. The permeability value of ZHM nanocrystals through Caco-2 cells increased 2.3-fold in comparison with ZHM coarse powder. Cumulative drug transport also increased at the end of the sampling period. Conclusion: Nanocrystal technology helps to increase the permeability of drug particles by increasing the saturation solubility.Öğe The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization(Galenos Publ House, 2022) Ugur Kaplan, Afife Busra; Ozturk, Naile; Cetin, Meltem; Vural, Imran; Oznuluer Ozer, TubaObjectives: Daidzein (DZ), a water-insoluble isoflavone, has many beneficial effects (anti-inflammatory, antioxidant, and anticancer effects, etc.) on human health. DZ has a very low oral bioavailability related to its physicochemical properties (low solubility, intense metabolism of DZ in the intestine and liver). This study aimed to prepare and in vitro characterize the nanosuspension formulations of DZ to improve the poor solubility and efficacy of DZ. Materials and Methods: DZ nanosuspension formulations were prepared with media milling technique using zirconium oxide beads as milling media. Pluronic F127 and polyvinylpyrrolidone (PVP) K30 (formulation A; F-A) and sodium dodecyl sulfate (SDS) (SDS + pluronic F127 + PVP K30; formulation B; F-B) were used as stabilizers. The nanosuspension formulations were evaluated for morphological properties, particle sizes, zeta potential, DZ content, saturation solubility, dissolution, and their cytotoxic effects on RG2 glioblastoma tumor cells. Results: F-A and F-B formulations were nanosized (in the range of about 181-235 nm) and had negative zeta potential values before and after lyophilization. The DZ content of F-A and F-B formulations were found to be 93.68 +/- 0.78% and 89.75 +/- 0.49%, respectively. Fourier transform infrared spectroscopy analysis showed that there was no significant interaction between DZ and the excipients. Differential scanning calorimetry and X-ray diffraction analyses confirmed no change in the crystal structure of DZ in F-A and F-B formulations. Conclusion: In this study, the nanosuspension formulations were successfully prepared and characterized in vitro. Nanosuspension formulations increased the saturation solubility, dissolution rate, and cytotoxic effect of DZ.Öğe Optimizing Niosomal Formulations for Enhanced Cellular Applications(Wiley, 2024) Cakir, Nilufer; Ozturk, Naile; Kara, Asli; Zarrabi, Ali; Mustafaoglu, NurThis study delves into the optimization of niosomal production for biological applications, focusing on their emerging role as amphiphilic nanoparticles derived from nonionic surfactants, poised at the forefront of biomedical research. We aimed to formulate and characterize a diverse array of niosomal nanoparticles, with particular emphasis on process-related parameters and physicochemical characteristics. Critical thresholds for size, polydispersity, and zeta potential were established to identify parameters crucial for optimal niosomal formulations through a comprehensive investigation of concentrations, sonication times, ingredient ratios, and surfactant types. Leveraging MODDE software, we generated 10 optimized formulations from preliminary parameter screening. The proposed experimental model design by the software exhibited acceptable similarity to the obtained experimental results (F-score: 0.83). The criteria for selection of the predicted experimental model formed based on targeted physicochemical considerations. To enhance half-life and penetration, especially in higher electrostatic regions like the central nervous system (CNS), we proposed a neutralized surface charge (-10 to 10 mV) while maintaining size within 100-200 nm and polydispersity below 0.5. Extended stability screening revealed periodic and extended Gaussian distributions for size and zeta potential to minimize flocculation and coagulation caused by neutralized surface charge. Notably, the cellular response performance of optimized niosomes was assessed via cellular binding, uptake, and viability in comparison with liposomes. Glioblastoma cell line (U-87) and granulocyte colony-stimulating factor (G-CSF) containing lymphoblastic leukemia cell line (NFS-60) were chosen to represent tumors developed in the CNS region and white blood cells, respectively, enabling a comprehensive comparative analysis with liposomes. The meticulous comparison between niosomes and liposomes revealed comparable cellular viability profiles on both U-87 and NFS-60 cell lines, highlighting their similarities in cellular interactions. Moreover, selected niosomal formulations demonstrated exceptional cellular uptake, either equaling or surpassing observed liposomal uptake. One of the most promising niosomes was selected and optimized to evaluate drug encapsulation performance of niosomes for further drug delivery adaptations by one of the chemotherapy drugs, paclitaxel (PTX). Cytotoxicity study was established with the most efficiently encapsulated niosomal condition with human-derived fibroblasts (HDFs) and U-87 as the representation of healthy and cancerous cell lines. Results demonstrated 1:100 diluted PTX-loaded niosome in the certain concentration demonstrated favorable toxicity in U-87 than original PTX at the same concentration while not disturbing healthy HDFs. These findings underscore the potential of niosomes for reliable drug delivery, challenging the dominance of liposomal vehicles and presenting economically viable nanocarriers with significant implications for advancing biomedical research.Öğe Preparation and evaluation of fast-dissolving albendazole sulfoxide and praziquantel-loaded polyvinylpyrrolidone nanofiber films by electrospinning(Elsevier, 2024) Gultekin, Yakup; Korkmaz, Cagla; Ozturk, Naile; Filazi, Ayhan; Deniz, Ahmet; Dog, Osman; Pezik, EsraAlbendazole sulfoxide (ALBSOX) and Praziquantel (PRZ) are broad-spectrum anthelmintic medications used in the treatment of both humans and animals that are challenging to manufacture for geriatric and pediatric populations and have poor oral bioavailability due to their low water solubility and high lipophilicity. To increase the solubility and bioavailability of the drugs, ALBSOX and PRZ-loaded nanofiber films were prepared using polyvinylpyrrolidone K90 (PVP), a non-toxic, inert polymer with high hydrophilic characteristics. SEM analysis of the produced ALBSOX and PRZ-loaded PVP nanofiber films revealed them to be uniform and smooth, with good uniformity and mechanical properties. The PVP nanofiber films of ALBSOX and PRZ disintegrated in phosphate buffer (pH 6.8) in less than 1 s and increased the solubility of ALBSOX and PRZ about five times compared to pure active ingredients. Furthermore, the prepared ALBSOX and PRZ-loaded PVP nanofiber films were found to have no cytotoxic effect in cell viability studies using L929 cells, and increased the protoscolicidal effect of the ALBSOX and PRZ combination approximately 2-fold in studies of Echinococcus granulosus protoscoleces. The findings of the present study reveal that the developed PVP nanofiber films have the potential to improve the dissolution profile and pharmacological efficacy of the ALBSOX and PRZ.Öğe Preparation of nanosuspensions of a 1,4-dihydropyridine-based mixed L-/T-type calcium channel blocker by combined precipitation and ultrasonication methods(Elsevier, 2023) Pezik, Esra; Gulsun, Tugba; Gunduz, Miyase Gozde; Sahin, Selma; Ozturk, Naile; Vural, ImranM3, a condensed 1,4-dihydropyridine (DHP) derivative, targets both L- and T-type calcium channels and therefore, stands as a promising antihypertensive drug candidate. This study aims to improve the poor solubility of M3 using nanocrystal technology (a combination of precipitation and ultrasonication methods) to enhance its oral bioavailability. Pre-formulation studies were performed and M3 nanosuspensions were prepared using different stabilizers (polyvinyl pyrrolidone K30, polyvinyl alcohol, SoluPlus & REG;) and surfactants (poloxamer 188, poloxamer 407, sodium deoxycholate, sodium lauryl sulfate) at different concentrations (0.05, 0.1, 0.5, 1.0, 2.0%, w/v). The optimum nanosuspension formulation was freeze-dried using different cryoprotectants (mannitol, trehalose, glucose, sucrose, dextran) at different ratios (1.25, 2.5, 5.0%, w/v). It was determined that the most suitable cryoprotectant and ratio was 5.0% trehalose, resulting in nanocrystals with a size of 320.2 & PLUSMN; 15.3 nm and a zeta potential of -27.4 & PLUSMN; 0.1 mV. The physicochemical properties of M3, poloxamer 188, physical mixture and freeze-dried nanocrystals were evaluated by XRD, DSC and FT-IR analyses. Characterization studies showed amorphization of M3 in the freeze-dried nanocrystals prepared with poloxamer 188. The result of equilibrium solubility and permeability studies results indicated that M3 could be a BCS class 4 compound. Cell culture studies using Caco-2 cells showed that M3 had no significant toxic effect on the cells and had a Papp value of 2.2 x 10-7 cm/s. Compared to coarse M3 powder freeze-dried M3 nanocrystals showed a 200-fold increase in solubility and a 28.6-fold increase in apparent permeability. The cytotoxic effect of M3 was also reduced by using poloxamers as stabilizers in the formulation. M3 nanosuspensions were found to be a promising candidate for the oral administration of M3 for the potential treatment of hypertension due to the increase in solubility and permeability which could enhance its oral bioavailability.Öğe Simultaneous determination of albendazole sulfoxide and praziquantel from PLGA nanoparticles and validation of new HPLC method(Marmara Univ, 2022) Gultekin, Yakup; Ozturk, Naile; Filazi, Ayhan; Deniz, Ahmet; Korkmaz, Cagla; Pezik, Esra; Barin, GozdeA simple, rapid and reproducible HPLC method has been developed and validated for the quantification of albendazole sulfoxide (ALBSOX) and praziquantel (PRZ), which can coexist in various dosage forms. Chromatographic separation was performed in gradient mode using a mobile phase consisting of an InertSustain (R) C18 column (150 x 4.6 mm, 5 mu m) and acetonitrile: water (v/v) at a flow rate of 1.0 mL/min. The active substance peaks were well separated and detected by a DAD detector at 217 nm. The HPLC method was linear for ALBSOX and PRZ in the concentration range of 0.1-50 mu g/mL. Limit of detection (LOD) was found to be 0.01 mu g/mL for ALBSOX and 0.009 mu g/mL for PRZ. The limit of quantification (LOQ) was found to be 0.03 mu g/mL for ALBSOX and 0.027 mu g/mL for PRZ. The developed HPLC method was validated based on ICH guidelines for specificity, linearity, system suitability, precision and accuracy. The method was applied for simultaneous quantification and characterization studies of ALBSOX and PRA in PLGA nanoparticles.Öğe Targeting prostate cancer with docetaxel-loaded peptide 563-conjugated PEtOx-co-PEI30%-b-PCL polymeric micelle nanocarriers(Springer Wien, 2023) Nezir, Ayca Ece; Bolat, Zeynep Busra; Ozturk, Naile; Kocak, Polen; Zemheri, Ebru; Gulyuz, Sevgi; Ozkose, Umut UgurProstate cancer is a global disease that negatively affects the quality of life. Although various strategies against prostate cancer have been developed, only a few achieved tumor-specific targeting. Therefore, a special emphasis has been placed on the treatment of cancer using nano-carrier-encapsulated chemotherapeutic agents conjugated with tumor-homing peptides. The targeting strategy coupling the drugs with nanotechnology helps to overcome the most common barriers, such as high toxicity and side effects. Prostate-specific membrane antigen has emerged as a promising target molecule for prostate cancer and shown to be targeted with high affinity by GRFLTGGTGRLLRIS peptide known as peptide 563 (P563). Here, we aimed to assess the in vitro and in vivo targeting efficiency, safety, and efficacy of P563-conjugated, docetaxel (DTX)-loaded polymeric micelle nanoparticles (P563-PEtOx-co-PEI30%-b-PCL-DTX) against prostate cancer. To this end, we analyzed the cytotoxic activity of P563-PEtOx-co-PEI30%-b-PCL and P563-PEtOx-co-PEI30%-b-PCL-DTX by a cell proliferation assay using PNT1A and 22Rv1 cells. We have also determined the targeting selectivity of P563-PEtOx-co-PEI30%-b-PCL-FITC by flow cytometry and assessed the induction of cell death by western blot and TUNEL assays for P563-PEtOx-co-PEI30%-b-PCL-DTX in 22Rv1 cells. To investigate the in vivo efficacy, we administered DTX in the free form or in polymeric micelle nanoparticles to athymic CD-1 nu/nu mice 22Rv1 xenograft models and performed histopathological analyses. Our study showed that targeting prostate cancer with P563-conjugated PEtOx-co-PEI30%-b-PCL polymeric micelles could exert a potent anti-cancer activity with low side effects.
