Kezban Ulubayram

EGF containing gelatin-based wound dressings.

In case of bulk loss of tissue or non-healing wounds such as burns, trauma, diabetic, decubitus and venous stasis ulcers, a proper wound dressing is needed to cover the wound area, protect the damaged tissue, and if possible to activate the cell proliferation and stimulate the healing process. In this study, synthesis of a novel polymeric bilayer wound dressing containing epidermal growth-factor (EGF) -loaded microspheres was aimed. For this purpose, a natural, nontoxic and biocompatible material, gelatin, was chosen as the underlying layer and various porous matrices in sponge form were prepared from gelatin by freeze-drying technique. As the external layer, elastomeric polyurethane membranes were used. Two different doses of EGF was added into the prepared gelatin sponges (1 and 15 microg/cm2) to activate cell proliferation. EGF addition was carried out either in free form or within microspheres to achieve prolonged release of EGF for higher efficiency. The prepared systems were tested in in vivo experiments on full-thickness skin defects created on rabbits. At certain intervals, wound areas were measured and tissues from wound areas were biopsied and processed for histological examinations. The wound areas decreased upon low-dose EGF application but the difference between the affects of free EGF and microsphere loaded EGF was not so distinct. Upon increasing the dose of EGF by a factor of 15, it was observed that controlled release of EGF from microspheres provided a higher degree of reduction in the wound areas. Histological investigations showed that the prepared dressings were biocompatible and did not cause any mononuclear cell infiltration or foreign body reaction. The structure of the newly formed dermis was almost the same as that of the normal skin.

Cytotoxicity evaluation of gelatin sponges prepared with different cross-linking agents

Gelatin is a natural polymer used in pharmaceutical and medical applications, especially in the production of biocompatible and biodegradable wound dressings and drug delivery systems. Gelatin granules hydrate, swell and solubilize in water, and rapidly degrade in vivo. The durability of these materials could, however, be prolonged by cross-linking by aldehydes, carbodiimides, and aldose sugars, but the biocompatibility of collagenous biomaterials is profoundly influenced by the nature and extent of cross-linking. In this study, gelatin sponges were prepared by using various cross-linkers such as glutaraldehyde (GA), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDAC), and D-fructose. The effects of the type and the amount of cross-linker on thermal and mechanical properties, stability, and cytotoxicity were investigated. The mechanical analysis data showed that an increase in the amount of GA in the sponge structures caused a slight increase in the modulus of elasticity but had almost no effect on the tensile strength. Increase in the EDAC concentration produced a maximum in the modulus of elasticity and tensile strength values. The stability of the sponges and the time required for complete degradation in aqueous media increased in parallel with the cross-linker content. In vitro studies carried out with fibroblast cells demonstrated a higher cell viability for the samples cross-linked with low concentrations of GA than for those cross-linked with EDAC.

Silk fibroin based antibacterial bionanotextiles as wound dressing materials.

New applications for medical biotextiles have been identified with the development of nanotechnological manufacturing technologies. Combination of nanotechnology and biotextile technology has resulted into a new field called bionanotextiles. Bionanotextiles are used in many areas which include wound dressings, bandages and tissue scaffolds. Silk fibroin (SF) from the cocoon of Bombyx mori, is one of the most favorable wound dressing materials due to its unique properties including biocompatibility, permeability, biodegradability, morphologic flexibility, and proper mechanical properties. The modification of antimicrobial properties of SFs can provide a barrier for bacterial penetration as wound dressing materials. In the present study, antibacterial polyethylenimine (PEI) (10, 20 and 30% (w/w)) was blended with SF and bionanotextiles were successfully fabricated by electrospinning. In addition, silk fibroin nanofibers were also functionalized with sulphate group in order to test whether they exhibit an antibacterial activity or not. Fibroin based bionanotextiles were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The cytotoxicity evaluations were carried out by L929 fibroblasts with MTT assay. The indirect cytotoxicity results demonstrate that all fibroin and PEI/fibroin extracts have no cytotoxicity on L929 cancer cell line. PEI/fibroin bionanotextiles showed strong antibacterial activities against gram positive Staphylococcus aureus and gram negative Pseudomonas aeruginosa.

Acrylic-based high internal phase emulsion polymeric monolith for capillary electrochromatography

The use of high internal phase emulsion polymers (polyHIPEs) for CEC applications has remained relatively unexplored. A few reports exist in the literature for the preparation of similar structures. In this study, polyHIPEs having high porosity, and interconnected open-cell structure, were introduced and evaluated as stationary phase for CEC. The polyHIPE monolithic columns were prepared by the in situ polymerization of isodecylacrylate (IDA) and divinylbenzene (DVB) in the continuous phase of a high internal phase emulsion (HIPE). Due to its well-defined polyHIPE structure with interconnected micron size spherical voids, the columns synthesized with different initiator concentrations were successfully used for the separation of alkylbenzenes. Furthermore, the columns indicated a strong electroosmotic flow (EOF) without any additional EOF generating monomer probably due to the presence of ionizable sulfate groups coming from the water-soluble initiator used in the preparation of polyHIPE matrix. The best chromatographic performance in the separation of alkylbenzenes was achieved by using 70% ACN in the mobile phase with high column efficiency (up to 200,000 plates/m).

Gelatin microspheres and sponges for delivery of macromolecules

Gelatin microspheres and gelatin sponges were prepared by coacervation and freeze drying techniques, respectively. Both systems were crosslinked with glutaraldehyde. The mean diameter of the microspheres were in the range of 40–80 mm and the mean pore size of the sponges was 130–220 mm depending on the preparation conditions. Bovine serum albumin (BSA) was added into the preparation solutions and entrapped in the microspheres and sponges. BSA addition to sponges was also achieved by addition of BSA-containing microspheres into the sponges. The release kinetics of BSA from the prepared systems were examined. Studies demonstrated that release is dependent on the amount of BSA present in the system and crosslinking densities of microspheres. It was concluded that gelatin microspheres and gelatin sponges are promising carrier matrices for macromolecules.

Brain targeting of Atorvastatin loaded amphiphilic PLGA-b-PEG nanoparticles.

The objective of this study was to develop polysorbate 80 coated and Atorvastatin loaded poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles and to investigate advantages of coating on nanoparticles for brain delivery of Atorvastatin. The nanoparticles were prepared by nanoprecipitation method. The effects of polymer concentration, PEG content and polysorbate 80 coating on the particle size, drug loading efficiency and release behaviour of nanoparticles were investigated. Additionally, cellular uptake and brain targeting of formulated nanoparticles were studied. Particle sizes were in the range of 30–172 nm depending on formulation parameters. Increasing the polymer concentration significantly increased the nanoparticle size. Decreasing the PEG content from 15% to 5% (w/w) in polymer composition increased the nanoparticle size from 69 to 172 nm. Both coated and uncoated polysorbate 80 nanoparticles were effectively internalised within the endothelial cells. Moreover, both types of nanoparticles were able to penetrate the blood brain barrier and reach the maximum in brain 1 h post injection. It was concluded that these nanoparticles are promising nanosystems for treatment of neurological disorders.

Polyurethanes: effect of chemical composition on mechanical properties and oxygen permeability

Abstract A series of polyether urethane films with varying hard/soft segment ratio were synthesized using toluene-2,4-diisocyanate (TDI) and polypropylene glycol (PPG) in order to evaluate them as biomaterials. In order to obtain medical purity the polymerization reactions were carried out in bulk without using any other ingredients such as solvent, catalyst, u.v. absorber, etc. The effects of chemical composition and the presence of the chain extender on some properties were examined. For the samples with higher TDI to PPG ratio, a decrease in ultimate elongation and an increase in tensile strength were observed. Addition of chain extender caused an increase in both. On the other hand, the ultimate elongation increased and tensile strength decreased with an increase in molecular weight of the PPG used. As the chemical compositions are changed by increasing the polyol content, an increase in oxygen permeability is also observed.

Nanofibers Based Antibacterial Drug Design, Delivery and Applications

Infections caused by microorganisms like bacteria, fungi, etc. are the main obstacle in healing processes. Conventional antibacterial administration routes can be listed as oral, intravenous/intramuscular, topical and inhalation. These kinds of drug administrations are faced with critical vital issues such as; more rapid delivery of the drug than intended which can result in bacterial resistance, dose related systemic toxicity, tissue irritation and finally delayed healing process that need to be tackled. Recently, studies have been focused on new drug delivery systems, overcoming resistance and toxicological problems and finally localizing the molecules at the site of action in a proper dose. In this regard, many nanotechnological approaches such as nanoparticulate therapeutic systems have been developed to address accompanying problems mentioned above. Among them, drug loaded electrospun nanofibers propose main advantages like controlled drug delivery, high drug loading capacity, high encapsulation efficiency, simultaneous delivery of multiple drugs, ease of production and cost effectiveness for pharmaceutical and biomedical applications. Therefore, some particular attention has been devoted to the design of electrospun nanofibers as promising antibacterial drug carrier systems. A variety of antibacterials e.g., biocides, antibiotics, quaternary ammonium salts, triclosan, metallic nanoparticles (silver, titanium dioxide, and zinc oxide) and antibacterial polymers (chitosan, polyethyleneimine, etc.) have been impregnated by various techniques into nanofibers that exhibit strong antibacterial activity in standard assays. This review highlights the design and delivery of antibacterial drug loaded nanofibers with particular focus on their function in the fields of drug delivery, wound healing, tissue engineering, cosmetics and other biomedical applications.

Preparation and In Vitro/In Vivo Evaluation of Cyclosporin A-Loaded Nanodecorated Ocular Implants for Subconjunctival Application

In terms of ocular drug delivery, biodegradable implant systems have several advantages including the ability to provide constant drug concentration at the target site, no necessity for surgical removal, and minimum systemic side effects. Cyclosporin A (CsA) is a neutral, hydrophobic, cyclic peptide of amino acids that frequently used for dry eye disease treatment. The aim of this study was to develop a nanoparticle-loaded implant system for sustained-release CsA delivery following subconjunctival implantation. Poly(lactide-co-glycolide) (85:15) or poly-ε-caprolactone (PCL) were used to prepare two different nanoparticle formulations. These nanoparticles loaded into PCL or poly(lactide-co-caprolactone) implant formulations were prepared by two different methods, which were molding and electrospinning. Size and zeta potential of nanoparticles were determined and the morphology of the formulations were investigated by scanning electron microscopy. CsA-loading efficiencies were calculated and the in vitro degradation and in vitro release studies were performed. MTT test was also performed using L929 fibroblast cells to evaluate the cytotoxicity of the formulations. PCL-PCL-NP-I formulation was implanted to Swiss Albino mice with induced dry eye syndrome to evaluate the efficacy. In vitro release studies showed that the release from the formulations continues between 30 and 60 days, and the cell viability was found to be 77.4%-99.0%. In vivo studies showed that healing is significantly faster in the presence of the selected implant formulation. Results indicated that nanodecorated implants are promising ocular carriers for controlled-release CsA application.

Properties of plasma-modified polyurethane surfaces

Abstract Polyurethane elastomers were prepared from toluene-2,4-diisocyanate (TDI), polypropylene glycol (PPG), and 1,3-propanediol by bulk polymerization without using a catalyst, solvent or any other ingredients. Chemical structures were examined by IR spectroscopy. The effects of chemical composition on the surface and bulk hydrophilicity were investigated. In the bulk an increase in water content with an increase in PPG/TDI molar ratio was observed. Contact angle measurements, however, showed an opposite hydrophilicity trend with the surfaces. Thermal studies revealed an increase in T g with an increase in TDI/PPG molar ratio. The polyurethane surfaces were modified by the plasma polymerization technique using two different chemicals: 2-hydroxyethyl methacrylate and hexamethyldisiloxane. The effects of these modifications on chemical composition, hydrophilicity and blood compatibility of the surfaces were tested.