Browsing by Subject "Drug delivery"

Now showing 1 - 20 of 23

Open Access
A microfluidics-assisted double-barreled nanobioconjugate synthesis ıntroducing aprotinin as a new moonlight nanocarrier protein: tested toward physiologically relevant 3d-spheroid models
(American Chemical Society, 2024-04-02) Nazir, Faiqa; Munir, Iqra; Yeşilöz, Gürkan
Proteins are promising substances for introducing new drug carriers with efficient blood circulation due to low possibilities of clearance by macrophages. However, such natural biopolymers have highly sophisticated molecular structures, preventing them from being assembled into nanoplatforms with manipulable payload release profiles. Here, we report a novel anticancer nanodrug carrier moonlighting protein, Aprotinin, to be used as a newly identified carrier for cytotoxic drugs. The Aprotinin-Doxorubicin (Apr-Dox) nanobioconjugate was prepared via a single-step microfluidics coflow mixing technique, a feasible and simple way to synthesize a carrier-based drug design with a double-barreled approach that can release and actuate two therapeutic agents simultaneously, i.e., Apr-Dox in 1:11 ratio (the antimetastatic carrier drug aprotinin and the chemotherapeutic drug DOX). With a significant stimuli-sensitive (i.e., pH) drug release ability, this nanobioconjugate achieves superior bioperformances, including high cellular uptake, efficient tumor penetration, and accumulation into the acidic tumor microenvironment, besides inhibiting further tumor growth by halting the urokinase plasminogen activator (uPA) involved in metastasis and tumor progression. Distinctly, in healthy human umbilical vein endothelial (HUVEC) cells, drastically lower cellular uptake of nanobioconjugates has been observed and validated compared to the anticancer agent Dox. Our findings demonstrate an enhanced cellular internalization of nanobioconjugates toward breast cancer, prostate cancer, and lung cancer both in vitro and in physiologically relevant biological 3D-spheroid models. Consequently, the designed nanobioconjugate shows a high potential for targeted drug delivery via a natural and biocompatible moonlighting protein, thus opening a new avenue for proving aprotinin in cancer therapy as both an antimetastatic and a drug-carrying agent.
Embargo
A novel acoustic modulation of oscillating thin elastic membrane for enhanced streaming in microfluidics and nanoscale liposome production
(Wiley-VCH Verlag GmbH & Co. KGaA, 2024-09-26) Vardin, Ali Pourabdollah; Aksoy, Faruk; Yeşilöz, Gürkan
Liposomes are widely utilized in therapeutic nanosystems as promising drug carriers for cancer treatment, which requires a meticulous synthesis approach to control the nanoprecipitation process. Acoustofluidic platforms offer a favorable synthesis environment by providing robust agitation and rapid mixing. Here, a novel high-throughput acoustofluidic micromixer is presented for a solvent and solvent-free synthesis of ultra-small and size-tunable liposomes. The size-tunability is achieved by incorporating glycerol as a new technique into the synthesis reagents, serving as a size regulator. The proposed device utilizes the synergistic effects of vibrating trapped microbubbles and an oscillating thin elastic membrane to generate vigorous acoustic microstreaming. The working principle and mixing mechanism of the device are explored numerically and experimentally. The platform exhibits remarkable mixing efficacy for aqueous and viscous solutions at flow rates up to 8000 µL/h, which makes it unique for high-throughput liposome formation and preventing aggregation. As a proof of concept, this study investigates the impact of phospholipid type and concentration, flow rate, and glycerol on the size and size distribution of liposomes. The results reveal a significant size reduction, from ≈900 nm to 40 nm, achieved by merely introducing 75% glycerol into the synthesis reagents, highlighting an innovative approach toward size-tunable liposomes.
Open Access
Artificial neural network modeling and simulation of in-vitro nanoparticle-cell interactions
(American Scientific Publishers, 2014) Cenk, N.; Budak, G.; Dayanik, S.; Sabuncuoglu, I.
In this research a prediction model for the cellular uptake efficiency of nanoparticles (NPs), which is the rate that NPs adhere to a cell surface or enter a cell, is investigated via an artificial neural network (ANN) method. An appropriate mathematical model for the prediction of the cellular uptake rate of NPs will significantly reduce the number of time-consuming experiments to determine which of the thousands of possible variables have an impact on NP uptake rate. Moreover, this study constitutes a basis for targeted drug delivery and cell-level detection, treatment and diagnosis of existing pathologies through simulating NP-cell interactions. Accordingly, this study will accelerate nanomedicine research. Our research focuses on building a proper ANN model based on a multilayered feed-forward back-propagation algorithm that depends on NP type, size, surface charge, concentration and time for prediction of cellular uptake efficiency. The NP types for in-vitro NP-healthy cell interaction analysis are polymethyl methacrylate (PMMA), silica and polylactic acid (PLA), all of whose shapes are spheres. The proposed ANN model has been developed on MATLAB Programming Language by optimizing a number of hidden layers (HLs), node numbers and training functions. The datasets are obtained from in-vitro NP-cell interaction experiments conducted by Nanomedicine and Advanced Technology Research Center. The dispersion characteristics and cell interactions with different NPs in organisms are explored using an optimal ANN prediction model. Simulating the possible interactions of targeted NPs with cells via an ANN model will be faster and cheaper compared to the excessive experimentation currently necessary.
Open Access
Bioinspired materials for regenerative medicine and drug delivery applications
(2016-10) Hamsici, Seren
The structural organization and functional capabilities of natural materials have inspired many technological and scientific developments. Biological systems are under constant pressure for innovation due to the constraints imposed by natural selection, which has allowed various organisms to surmount engineering challenges in ways that can scarcely be matched by modern science. Biomimetics or bioinspiration is a field that focuses on the adaptation of engineering principles observed in biological models to fabricate materials capable of circumventing longstanding problems in fields such as energy and medicine. This transition from biological systems has facilitated the design of effective materials, structures or processes within the range of nature’s adaptations and strategies. In the first study of this thesis, I describe the development of a bioactive scaffold composed of adamantyl-conjugated, laminin-derived bioactive IKVAV peptide molecules enmeshed in electrospun cyclodextrin nanofiber (CDNFs). Accordingly, host-guest interactions between adamantyl groups on peptide termini and cyclodextrin molecules on electrospun nanofiber surfaces were utilized to produce a composite material for the treatment of neurodegenerative disorders. Electrospun CDNFs provided a 3-dimensional environment conductive for the growth of PC12 cells and expressed functionalized bioactive epitopes on their surfaces to enhance the differentiation of neural progenitors. In addition, CDNFs further supported neural growth through their highly aligned mesh structure. Neural bIII tubulin and synaptophysin I gene expression levels significantly increased when PC12 cells were cultured on aligned and IKVAV-functionalized CDNFs. Neurite extension of PC12 cells also increased significantly when cultured on aligned and IKVAVfunctionalized CDNFs when compared to random and unfunctionalized electrospun CDNFs. As such, these nanofibers are able to effectively induce the neural differentiation of PC-12 cells through the physical and biochemical signals provided by their structure and bioactive sequence. The second part of the present thesis focuses on the local delivery of gemcitabine, a cytotoxic cancer drug that is rapidly degraded in plasma and cannot be encapsulated in conventional delivery vesicles due to its highly hydrophobic nature. In order to overcome these limitations, gemcitabine was coupled with Fmoc-Gly and integrated into a peptide-based nanocarier system in order to control drug concentration within the therapeutic range and minimize the adverse effects. Two oppositely-charged amyloid inspired peptides (Fmoc-AIPs) were chosen as drug carrier systems. These molecules self assemble into nanofiber structures at physiological conditions through non-covalent interactions. Overall, the present thesis demonstrates the significance of peptide-based materials for the purpose of designing functional bioinspired/biomimetic materials for various cellular applications such as tissue engineering and drug delivery. The complexity of nature necessitates the design of biomaterials that can mimic the cellular microenvironment for the treatment of diseases, and further insight into natural processes will no doubt enhance our ability to overcome the engineering challenges presented by modern medicine.
Open Access
Biomimetic cell membrane-coated poly(lactic-co-glycolic acid) nanoparticles for biomedical applications
(John Wiley & Sons, Inc., 2022-11-02) Jan, N.; Madni, A.; Khan, S.; Shah, H.; Akram, F.; Khan, A.; Ertas, D.; Bostanudin, M. F.; Contag, C. H.; Ashammakhi, N.; Ertaş, Yavuz Nuri
Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are commonly used for drug delivery because of their favored biocompatibility and suitability for sustained and controlled drug release. To prolong NP circulation time, enable target-specific drug delivery and overcome physiological barriers, NPs camouflaged in cell membranes have been developed and evaluated to improve drug delivery. Here, we discuss recent advances in cell membrane-coated PLGA NPs, their preparation methods, and their application to cancer therapy, management of inflammation, treatment of cardiovascular disease and control of infection. We address the current challenges and highlight future research directions needed for effective use of cell membrane-camouflaged NPs
Open Access
“Clicked” Porphyrin-cucurbituril conjugate: a new multifunctional supramolecular assembly based on triglycosylated porphyrin and Monopropargyloxycucurbit[7]uril
(Wiley-VCH Verlag, 2018) Koç, Ahmet; Khan, Rehan; Tuncel, Dönüş
The design, synthesis, and characterization of a new multifunctional supramolecular assembly based on a photoactive glycosylated porphyrin and covalently attached monofunctionalized cucurbit[7]uril (CB7) are reported. To obtain the target supramolecular assembly, azido-functionalized tetraphenylporphyrin (TPP) was used as a building block. TPP was first glycosylated by copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, then a monopropargyloxy-functionalized-CB7 unit was conjugated to glycosylated TPP with a second CuAAC reaction. The host-guest chemistry of the assembly was investigated by 1H NMR experiments to establish the availability of the CB7 as a host. The imidazole-based guest, which is known to have high affinity toward CB7, was observed to form inclusion complex with CB7. It was also demonstrated that this supramolecular assembly can serve as an efficient photosensitizer for the generation of singlet oxygen.
Open Access
Conjugated polymer nanoparticles for cell labelling, imaging and drug delivery
(European Association for Chemical and Molecular Sciences, 2012-08) Tuncel, Dönüş; İbrahimova, Vusela; Gezici, Özlem
Nanoparticles based on conjugated polymers are emerging as a new class of luminescent nanoparticles. These nanoparticles have many potential applications including imaging agents, biosensors, and photonics owing to their high quantum yields, high molar absorptivity, photo stability and easy synthesis. The recent cell assay studies have also showed that these nanoparticles were not cytotoxic.4Moreover, conjugated polymer nanoparticles can be modified easily to deliver therapeutic agents such as cancer drugs, genetic materials (e.g. RNA, siRNA) and biomolecules to the desired targets. Here, we present the resent studies in our lab involving the synthesis and applications of nanoparticles using various conjugated polymers which emit blue, green, yellow and red. In order to obtain shape-persistent and stable nanoparticles, a novel method was developed in which the nanoparticles were prepared either via Cu-catalyzed or cucurbit[6]uril (CB6)-catalyzed click reactions between azide groups containing hydrophobic fluorene-based conjugated polymers and a hydrophilic diaminodialkyne containing cross-linker. Through the click reaction, not only does the cross-linking confer stability, but it also introduces functional groups, such as triazoles and amines, to the nanoparticles. TEM images of the nanoparticles also showed that they display very interesting morphologies. Incorporation of hydrophilic functional groups to the hydrophobic conjugated polymers resulted in a distinct phase separation, producing Janus-like or patchy particles.
Open Access
Contactless pulsed and continuous microdroplet release using photothermal liquid crystals
(Wiley-VCH Verlag GmbH & Co. KGaA, 2022-10-24) Beyazkilic, P.; Akçimen, Samet; Elbüken, Çağlar; Ortaç, Bülent; Cai, S.; Bukusoglu, E.
Targeted, on-demand delivery has been of interest using materials responsive to environmental stimuli. A delivery technique based on precise release of aqueous microdroplets from a liquid crystal (LC) medium with contactless stimulation is presented. A nematic LC is doped with a photothermal dye that produces heat under near IR light exposure. The heat is used to overcome the elastic strains in the LC phase, promoting the release of initially entrapped water droplets to the neighboring aqueous solution. Designing the geometry of LC-based emulsions and tuning the light intensity and position allows for manipulation of the release in two distinct modes defined as pulsated and continuous. In the pulsated mode, water droplets are released transiently from the casted water-in-LC emulsion layer based on sweeping by the moving isotropic-nematic phase boundary controlled by light. In the continuous mode, water droplets are ejected continuously from a droplet-shaped water-in-LC emulsion, due to a heating-induced internal flow controlled by light. The droplet release by contactless stimulation is used for the on-demand dosing of dopamine and its oxidizing reagent from isolated reservoirs to obtain an in situ reaction signal for a hydrogen peroxide assay. A new dual-mode release system developed with photothermal LCs holds potential in drug release, controlled mixing, and photothermal therapy
Open Access
Cooperative engulfment of nanoparticles by membranes and vesicles
(Institute of Physics Publishing Ltd., 2024-10-01) Bahrami, Arash; Bahrami, Amir Houshang
Cellular uptake and expulsion of nanoparticles and viruses often involves a substantial particle concentration at the cell membrane. These particles, many of which are distributed across the cell at relatively large distances, cooperate to enter or exit the cell, highlighting the importance of engulfment cooperativity. Here, we explore the cooperative entry and exit of two and multiple distant nanoparticles to and from curved vesicles, representing cellular endocytosis and exocytosis, respectively. We discover indirect engulfment cooperativity between distant nanoparticles wrapped by vesicles, driven by vesicle curvature, which is absent for particles engulfed by a flat bilayer. For the cooperative entry of two identical particles into the vesicle, we identify a counter-intuitive symmetry-breaking in which one fully-engulfed and one non-engulfed particle is more likely than two fully-engulfed or two non-engulfed particles. As a result, with a high concentration of closely-sized external particles, only half of the particles are expected to be successfully internalized by the vesicle, while the remaining half remains unwrapped, and partially engulfed particles are unlikely. In contrast, the cooperative exit of internal particles from the vesicle is characterized by the simultaneous partial engulfment of the particles that are continuously wrapped by the vesicle. This explains how evolution has harnessed membrane curvature for the simultaneous budding of multiple viral particles, a crucial step in viral infection. Our findings for the cooperative entry of multiple particles have significant implication for achieving efficient drug concentration in drug delivery applications.
Open Access
Cucurbit[7]uril-anchored porphyrin-based multifunctional molecular platform for photodynamic antimicrobial and cancer therapy
(American Chemical Society, 2019) Özkan, Melis; Kumar, Yogesh; Keser, Yağmur; Hadi, Seyed E.; Tuncel, Dönüş
Here we report a photoactive supramolecular assembly that is multifunctional and constructed by covalently linking four receptor molecules (cucurbit[7]uril) to a porphyrin derivative with suitable linkers. While this molecular platform serves very efficiently as a light-triggered broad-spectrum antibacterial agent, owing to its negligible dark cytotoxicity and the presence of host molecules (CB7), it can also be utilized as a vehicle to carry drug molecules for a combined chemo and photodynamic cancer therapy.
Open Access
Development of an aprotinin-based novel nano-bioconjugate utilizing microfluidics via 3D cancer spheroid models
(2024-08) Nazir, Faiqa
Proteins are promising substances for introducing new drug carriers with efficient blood circulation due to low possibilities of clearance by macrophages. However, such natural biopolymers have highly sophisticated molecular structures, preventing them from being assembled into nano-platforms with manipulable payload release profiles. Here, we announce a novel anti-cancer nano-drug carrier moonlighting protein, Aprotinin, to be used as a newly identified carrier for cytotoxic drugs. The Aprotinin-Dox orubicin (Apr-Dox) nano-bioconjugate was prepared via a single-step microfluidics co-flow mixing technique; a feasible and simple way to synthesize a carrier-based drug design with a double-barreled approach that can release and actuate two therapeutic agents simultaneously i.e., Apr-Dox in 1:11 ratio (aprotinin an anti-metastatic carrier drug and chemotherapeutic drug DOX). With a significant stimuli-sensitive (i.e. pH) drug release ability, this nanobioconjugate achieves superior bio-performances including high cellular uptake, efficient tumor penetration and accumulation into acidic tumor microenvironment, as well as inhibiting further tumor growth by halting the urokinase plasminogen activator (uPA) involved in metastasis and tumor progression. Distinctly, in healthy human umbilical vein endothelial (HUVEC) cells, drastically lower cellular uptake of nano-bioconjugate has been observed and validated compared to anticancer agent Dox. Our findings demonstrate an enhanced cellular internalization of nano-bioconjugates towards breast cancer, prostate cancer, and lung cancer both in vitro and in physiologically relevant biological 3D-spheroid models. Consequently, the designed nano-bioconjugate shows a high potential for targeted drug delivery via natural and biocompatible moonlighting protein, thus opening a new avenue for proving aprotinin in cancer therapy both as an anti-metastatic and drug-carrying agent.
Embargo
Diagnostic, therapeutic, and theranostic multifunctional microneedles
(Wiley-VCH Verlag GmbH & Co. KGaA, 2024-06-26) Ertaş, Yavuz Nuri; Ertaş, Derya; Erdem, Ahmet; Segujja, Farouk; Dulchavsky, Scott; Ashammakhi, Nureddin
Microneedles (MNs) have maintained their popularity in therapeutic and diagnostic medical applications throughout the past decade. MNs are originally designed to gently puncture the stratum corneum layer of the skin and have lately evolved into intelligent devices with functions including bodily fluid extraction, biosensing, and drug administration. MNs offer limited invasiveness, ease of application, and minimal discomfort. Initially manufactured solely from metals, MNs are now available in polymer-based varieties. MNs can be used to create systems that deliver drugs and chemicals uniformly, collect bodily fluids, and are stimulus-sensitive. Although these advancements are favorable in terms of biocompatibility and production costs, they are insufficient for the therapeutic use of MNs. This is the first comprehensive review that discusses individual MN functions toward the evolution and development of smart and multifunctional MNs for a variety of novel and impactful future applications. The study examines fabrication techniques, application purposes, and experimental details of MN constructs that perform multiple functions concurrently, including sensing, drug-molecule release, sampling, and remote communication capabilities. It is highly likely that in the near future, MN-based smart devices will be a useful and important component of standard medical practice for different applications.
Open Access
Drug delivery system based on cyclodextrin-naproxen inclusion complex incorporated in electrospun polycaprolactone nanofibers
(Elsevier, 2014) Canbolat, M. F.; Celebioglu A.; Uyar, Tamer
In this study, we select naproxen (NAP) as a reference drug and electrospun poly (e-caprolactone) (PCL) nanofibers as a fibrous matrix for our drug-delivery system. NAP was complexed with beta-cyclodextrin (βCD) to form inclusion complex (NAP-βCD-IC) and then NAP-βCD-IC was incorporated into PCL nanofibers via electrospinning. The incorporation of NAP without CD-IC into electrospun PCL was also carried out for a comparative study. Our aim is to analyze the release profiles of NAP from PCL/NAP and PCL/NAP-βCD-IC nanofibers and we investigate the effect of CD-IC on the release behavior of NAP from the nanofibrous PCL matrix. The characterization of NAP-βCD-IC and the presence of CD-IC in PCL/NAP-βCD-IC nanofibers were studied by FTIR, XRD, TGA, NMR and SEM. The SEM imaging of the electrospun PCL/NAP and PCL/NAP-βCD-IC nanofibers reveal that the average fiber diameter of these nanofibers is around 300. nm, in addition, the aggregates of CD-IC in PCL/NAP-βCD-IC nanofibers is observed. The release study of NAP in buffer solution elucidate that the PCL/NAP-βCD-IC nanofibers have higher release amount of NAP than the PCL/NAP nanofibers due to the solubility enhancement of NAP by CD-IC.
Open Access
Dual functionality of conjugated polymer nanoparticles as an anticancer drug carrier and a fluorescent probe for cell imaging
(Royal Society of Chemistry, 2014) Gezici, Ö.; Durmaz, I.; Güven, E. B.; Ünal, Ö.; Özgün, A.; Cetin Atalay, R.; Tuncel, D.
Multifunctional nanoparticles based on a green emitting, hydrophobic conjugated polymer, poly[(9,9-bis{propeny}fluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1,3}-thiodiazole)] (PPFBT), that acts both as a fluorescent reporter and a matrix to accommodate an anti-cancer compound, camptothecin (CPT), were prepared, characterized and their potential as a fluorescent probe for cell imaging and as a drug delivery vehicle were evaluated via in vitro cell assays. The cell viability of human hepatocellular carcinoma cell line (Huh7) was investigated in the absence and presence of CPT with sulforhodamine B (SRB) and real-time cell electronic sensing (RT-CES) cytotoxicity assays.
Open Access
Efficient production and enhanced tumor delivery of engineered extracellular vesicles
(Elsevier Ltd, 2016) Watson, D. C.; Bayik D.; Srivatsan, A.; Bergamaschi, C.; Valentin, A.; Niu, G.; Bear, J.; Monninger, M.; Sun, M.; Morales-Kastresana, A.; Jones, J. C.; Felber, B. K.; Chen, X.; Gurse,l I.; Pavlakis, G. N.
Extracellular vesicles (EV), including exosomes and microvesicles, are nano-sized intercellular communication vehicles that participate in a multitude of physiological processes. Due to their biological properties, they are also promising candidates for the systemic delivery of therapeutic compounds, such as cytokines, chemotherapeutic drugs, siRNAs and viral vectors. However, low EV production yield and rapid clearance of administered EV by liver macrophages limit their potential use as therapeutic vehicles. We have used a hollow-fiber bioreactor for the efficient production of bioactive EV bearing the heterodimeric cytokine complex Interleukin-15:Interleukin-15 receptor alpha. Bioreactor culture yielded ∼40-fold more EV per mL conditioned medium, as compared to conventional cell culture. Biophysical analysis and comparative proteomics suggested a more diverse population of EV in the bioreactor preparations, while serum protein contaminants were detectable only in conventional culture EV preparations. We also identified the Scavenger Receptor Class A family (SR-A) as a novel monocyte/macrophage uptake receptor for EV. In vivo blockade of SR-A with dextran sulfate dramatically decreased EV liver clearance in mice, while enhancing tumor accumulation. These findings facilitate development of EV therapeutic methods. © 2016
Open Access
Electroless synthesis of 3nm wide alloy nanowires inside Tobacco mosaic virus
(2012) Balci, S.; Hahn, K.; Kopold P.; Kadri, A.; Wege, C.; Kern, K.; Bittner, A.M.
We show that 3nm wide cobaltiron alloy nanowires can be synthesized by simple wet chemical electroless deposition inside tubular Tobacco mosaic virus particles. The method is based on adsorption of Pd(II) ions, formation of a Pd catalyst, and autocatalytic deposition of the alloy from dissolved metal salts, reduced by a borane compound. Extensive energy-filtering TEM investigations at the nanoscale revealed that the synthesized wires are alloys of Co, Fe, and Ni. We confirmed by high-resolution TEM that our alloy nanowires are at least partially crystalline, which is compatible with typical Co-rich alloys. Ni traces bestow higher stability, presumably against corrosion, as also known from bulk CoFe. Alloy nanowires, as small as the ones presented here, might be used for a variety of applications including high density data storage, imaging, sensing, and even drug delivery. © 2012 IOP Publishing Ltd.
Open Access
Electrospinning of cyclodextrin functional nanofibers for drug delivery applications
(MDPI AG, 2019) Topuz, Fuat; Uyar, Tamer
Electrospun nanofibers have sparked tremendous attention in drug delivery since they can offer high specific surface area, tailored release of drugs, controlled surface chemistry for preferred protein adsorption, and tunable porosity. Several functional motifs were incorporated into electrospun nanofibers to greatly expand their drug loading capacity or to provide the sustained release of the embedded drug molecules. In this regard, cyclodextrins (CyD) are considered as ideal drug carrier molecules as they are natural, edible, and biocompatible compounds with a truncated cone-shape with a relatively hydrophobic cavity interior for complexation with hydrophobic drugs and a hydrophilic exterior to increase the water-solubility of drugs. Further, the formation of CyD-drug inclusion complexes can protect drug molecules from physiological degradation, or elimination and thus increases the stability and bioavailability of drugs, of which the release takes place with time, accompanied by fiber degradation. In this review, we summarize studies related to CyD-functional electrospun nanofibers for drug delivery applications. The review begins with an introductory description of electrospinning; the structure, properties, and toxicology of CyD; and CyD-drug complexation. Thereafter, the release of various drug molecules from CyD-functional electrospun nanofibers is provided in subsequent sections. The review concludes with a summary and outlook on material strategies
Open Access
Electrospinning of cyclodextrin functionalized nanofibers and their applications
(2016-08) Aytaç, Zeynep
Electrospinning is a widely used versatile method to produce nanofibers with high surface to volume ratio and porous structure. Owing to the unique properties, electrospun nanofibers are of great importance as a carrier matrix for drugs; antioxidant, and antibacterial agents, flavour/fragrances. Though polymers are material of choice for producing electrospun nanofibers, it is likely to obtain nanofibers from low molecular weight molecules. Cyclodextrin (CDs) are intriguing molecules having the capability of forming inclusion complex (IC) with numerous guest molecules such as drugs, food additives, flavour/fragrances, antioxidant and antibacterial agents. Therefore, CD-ICs enhance solubility, reduce volatility, and provide controlled release of the guest molecules. Integrating CD-ICs with electrospinning opens a new door to produce remarkable materials. In this thesis, nanofibers containing CD-ICs of bioactive agents including antioxidant/antibacterial and flavour/fragrance molecules were produced via electrospinning technique. Firstly, CD-ICs of antioxidant/antibacterial compounds (gallic acid, α-tocopherol, quercetin, and thymol) were synthesized and then, added into polylactic acid or zein solutions to produce CD-IC incorporated electrospun polymeric nanofibers. Afterwards, the release behavior, antioxidant and antibacterial activity of these nanofibers were investigated. In addition, the potential use of these nanofibers as active food packaging and delivery material was revealed by packing meat samples by these nanofibers. Secondly, electrospun nanofibers were developed as a releasing material from CD-ICs of volatile flavour/fragrance molecules (geraniol, limonene, and linalool) without using polymeric matrix. The preservation of volatile compounds is shown to be possible to a great extent with antibacterial CD-IC nanofibers. Furthermore, the shelf life of flavour/fragrance molecules has been enhanced at least 50 days by CD-IC nanofibers. Finally, for the first time in the literature core-shell nanofibers were designed by using CD-IC of curcumin, an antioxidant molecule and polylactic acid solutions as core and shell, respectively. The ability of core-shell nanofibers as a drug delivery carrier was suggested by release and antioxidant activity tests. To conclude, CD-IC incorporated electrospun nanofibers produced by three different approach is shown to be used as efficient material for various applications particularly for food packaging and drug delivery.
Open Access
Examination of fabrication conditions of acrylate-based hydrogel formulations for doxorubicin release and efficacy test for hepatocellular carcinoma cell
(Taylor and Francis., 2014) Bayramoglu, G.; Gozen, Damla; Ersoy, G.; Ozalp, V. C.; Akcali, K. C.; Arica, M. Y.
The objective of the present study was to develop 2-hydroxypropyl methacrylate-co-polyethylene methacrylate [p(HPMA-co-PEG-MEMA)] hydrogels that are able to efficiently entrap doxorubicin for the application of loco-regional control of the cancer disease. Systemic chemotherapy provides low clinical benefit while localized chemotherapy might provide a therapeutic advantage. In this study, effects of hydrogel properties such as PEG chains length, cross-linking density, biocompatibility, drug loading efficiency, and drug release kinetics were evaluated in vitro for targeted and controlled drug delivery. In addition, the characterization of the hydrogel formulations was conducted with swelling experiments, permeability tests, Fourier transform infrared, SEM, and contact angle studies. In these drug-hydrogel systems, doxorubicin contains amine group that can be expected a strong Lewis acid-base interaction between drug and polar groups of PEG chains, thus the drug was released in a timely fashion with an electrostatic interaction mechanism. It was observed that doxorubicin release from the hydrogel formulations decreased when the density of cross-linking, and drug/polymer ratio were increased while an increase in the PEG chains length of the macro-monomer (i.e. PEG-MEMA) in the hydrogel system was associated with an increase in water content and doxorubicin release. The biocompatibility of the hydrogel formulations has been investigated using two measures: cytotoxicity test (using lactate dehydrogenase assay) and major serum proteins adsorption studies. Antitumor activity of the released doxorubicin was assessed using a human SNU398 human hepatocellular carcinoma cell line. It was observed that doxorubicin released from all of our hydrogel formulations which remained biologically active and had the capability to kill the tested cancer cells.
Open Access
Microfluidic device for synthesis of chitosan nanoparticles
(ASME, 2013) Çetin, Barbaros; Taze, Serdar; Asik, M.D.; Tuncel, S.A.
Chitosan nanoparticles have a biodegradable, biocompatible, non-toxic structure, and commonly used for drug delivery systems. In this paper, simulation of a microfluidic device for the synthesis of chitosan nanoparticle is presented. The flow filed together with the concentration field within the microchannel network is simulated using COMSOL Multiphysics® simulation environment. Different microchannel geometries are analyzed, and the mixing performance of these configurations are compared. As a result, a 3D design for a microfluidics platform which includes four channel each of which performs the synthesis in parallel is proposed. Future research directions regarding the fabrication of the microfluidic device and experimentation phase are addressed and discussed. Copyright © 2013 by ASME.