Mehlika Pulat

5-fluorouracil encapsulated chitosan nanoparticles for pH-stimulated drug delivery: evaluation of controlled release kinetics

Nanoparticles consisting of human therapeutic drugs are suggested as a promising strategy for targeted and localized drug delivery to tumor cells. In this study, 5-fluorouracil (5-FU) encapsulated chitosan nanoparticles were prepared in order to investigate potentials of localized drug delivery for tumor environment due to pH sensitivity of chitosan nanoparticles. Optimization of chitosan and 5-FU encapsulated nanoparticles production revealed 148.8±1.1 nmand 243.1±17.9 nmparticle size diameters with narrow size distributions, which are confirmed by scanning electron microscope (SEM) images. The challenge was to investigate drug delivery of 5-FU encapsulated chitosan nanoparticles due to varied pH changes. To achieve this objective, pH sensitivity of prepared chitosan nanoparticle was evaluated and results showed a significant swelling response for pH 5 with particle diameter of ∼450 nm. In vitro release studies indicated a controlled and sustained release of 5-FU from chitosan nanoparticles with the release amounts of 29.1-60.8% due to varied pH environments after 408 h of the incubation period. pH sensitivity is confirmed by mathematical modeling of release kinetics since chitosan nanoparticles showed stimuli-induced release. Results suggested that 5-FU encapsulated chitosan nanoparticles can be launched as pH-responsive smart drug delivery agents for possible applications of cancer treatments

Relationship of Surface Characteristics to Cellular Attachment in PU and PHEMA

Adhesion characteristics of fibroblastic Baby Hamster Kidney (BHK) cells and epithelial Madine Darby Kidney (MDBK) cells on polyurethane (PU) and polyhydroxyethylmethacrylate (PHEMA) based surfaces have been studied. PU surfaces were prepared by a classical solvent-casting procedure of Pellethane® solution that contains different types of solvents, i.e., THF, dioxane and their compositions. PHEMA based surfaces were obtained by bulk polymerization of respective comonomers (HEMA, acrylic acid, AA, and dimethylaminoethylmethacrylate, DMAEMA) in the presence of the crosslinker. Thus, a number of polymeric surfaces were obtained with different surface charges (COO- and NH+ 4) and with different surface free energies in a range between 60-82 ergs/cm2. Surface properties of these membranes were characterized by equilibrium water contents, air and octane contact angles, surface free energies, SEM photographs and ATR-FTIR spectra. Interactions of BHK and MDBK cells with the surfaces were examined in stationary culture conditions which were carried out in MEM supplemented with fetal calf serum. The observations strongly suggested that the chemical and/or physical properties of membrane surface and morphology of the cell control the degree of cell adhesion to the PU and PHEMA based membranes.

Surface modification of PU membranes by graft copolymerization with acrylamide and itaconic acid monomers

Abstract To improve water wettability of polyurethane (PU), graft copolymerization of acrylamide (AAm) and itaconic acid (IA) was performed using benzoyl peroxide (BO) initiator. The grafting reaction was carried out by placing the membranes in aqueous solutions of Aam and IA at constant temperatures. Variations of graft yield with time, temperature, initiator and monomer concentrations were investigated. The optimum temperature, polymerization time, initiator and monomer concentrations for AAm were found to be 80°C, 2 h, 4.0×10 −2 M and 1.5 M and for IA, 80°C, 1 h, 4.0×10 −2 M and 1.5 M, respectively. The membranes were characterized by FTIR spectroscopy and scanning electron microscopy (SEM) analysis and the effect of grafting on equilibrium water content (EWC) of PU membranes was obtained by swelling measurements.

Sequential antibiotic and growth factor releasing chitosan-PAAm semi-IPN hydrogel as a novel wound dressing

The aim of this study is to prepare a novel wound dressing material which provides burst release of an antibiotic in combination with sustained release of growth factor delivery. This might be beneficial for the prevention of infections and to stimulate wound healing. As a wound dressing material, the semi-interpenetrating network (semi-IPN) hydrogel based on polyacrylamide (PAAm) and chitosan (CS) was synthesized via free radical polymerization. Ethylene glycol dimethacrylate was used for cross-linking of PAAm to form semi-IPN hydrogel. The hydrogel shows high water content (∼1800%, in dry basis) and stable swelling characteristics in the pH range of the wound media (∼4.0–7.4). The antibiotic, piperacillin–tazobactam, which belongs to the penicillin group was loaded into the hydrogel. The therapeutic serum dose of piperacillin–tazobactam for topic introduction was reached at 1st hour of the release. Additionally, in order to increase the mitogenic activity of hydrogel, epidermal growth factor (EGF) was embedded into the CS–PAAm in different amounts. Cell culture studies were performed with L929 mouse fibroblasts and the simulated cell growth was investigated by 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide assay. The successful sustained release behavior of CS–PAAm hydrogel for EGF maintained the presence of EGF in the culture up to 5 days and the highest mitochondrial activities were recorded for the 0.4 μg EGF-loaded/mg of hydrogel group. In conclusion, CS–PAAm semi-IPN hydrogel loaded with piperacillin–tazobactam and EGF could be proposed for an effective system in wound-healing management.

Fluconazole release from hydrogels including acrylamide-acrylic acid-itaconic acid, and their microbiological interactions

Polyacrylamide (PAAm), polyacrylic acid (PAA), poly(acrylamide-co-itaconic acid) (PAAmIA) and poly(acrylic acid-co-itaconic acid) (PAAIA) hydrogels were prepared via free-radical polymerization using ethylene glycol dimethacrylate (EGDMA) as cross-linker. The variations of swelling percentages with time and pH were determined for these hydrogels at 37°C. PAAmIA was found as the most swollen hydrogel at pH 4.0. SEM micrographs were taken to observe the morphology of the hydrogels. The less swollen hydrogel, PAAIA, displays less porosity relative to PAAmIA hydrogel. Fluconazole was entrapped into PAAmIA and PAAIA hydrogels and the release was investigated in Britton–Robinson buffer solution (BR) at pH 4.0 and 37°C. The kinetic release parameters of the hydrogels, n and k, were calculated and Fickian-type diffusion was established for PAAmIA, which releases Fluconazole faster than PAAIA hydrogel. Therapeutic range was reached in the first hour for both hydrogels. Microbiological interactions of hydrogels were also studied in vitro in vaginal medium. It is found that Fluconazole entrapped in hydrogels inhibited the growth of Candida albicans.

Structural and surface properties of polyurethane membranes of different porosities

Abstract The structural and surface properties of polyurethane (PU) membranes prepared by a classical solvent-casting method were tested. A number of casting solutions of Pellethane®, in dimethylformamide, dioxan, tetrahydrofuran and their mixtures, were used to obtain a series of PU membranes of different porosities. Structural properties of the membranes were investigated by scanning electron microscopy and surface free energies were calculated from contact-angle measurements. By changing the composition and type of casting solution, different physical, chemical and surface characteristics were obtained.

Adsorption of Bovine Serum Albumin onto Surface-Modified Polyhydroxyethyl Methacrylate Beads

The adsorption of bovine serum albumin (BSA) onto poly(2-hydroxyethyl methacrylate) (PHEMA) beads modified by using the pair of hexamethylene diisocyonate–suberic acidbis-N-hydroxy succinimide has been studied as a function of protein concentration and adsorption time. The adsorption studies were carried out in phosphate buffer solution (PBS) at pH = 7.4. The isotherm data have been analysed using the Langmuir model and the adsorption parameters Q0 and b were calculated. It is determined that the adsorbed amount of BSA increases by the increase of the adsorption time and BSA concentration until a certain value. PHEMA beads were characterized by using FTIR spectra and SEM analysis. The adsorption of BSA onto PHEMA beads were clearly observed from SEM micrographs. The swelling tests of the beads were performed at 37°C in PBS.

Pantoprazole-Na Release from Poly(acrylamide-co-crotonic acid) and Poly(acrylic acid-co-crotonic acid) Hydrogels

Poly(acrylamide-co-crotonic acid) (PAAmCA), poly(acrylic acid-co-crotonic acid) (PAACA), PAA and PAAm hydrogels were prepared by free radical polymerization and ethylene glycol dimethacrylate (EGDMA) as a crosslinker. The variations of swelling values (%) with time, temperature, and pH were determined for four types of hydrogels. The PAACA hydrogel was swollen 2300% at pH = 7.4 and 37°C. The drug release from pantoprazole-Na loaded PAACA and PAAmCA hydrogels was followed at pH = 7.4, 37°C for 30 h. The release from PAACA hydrogel was faster than that from PAAmCA hydrogel; therapeutic levels for both hydrogels are obtained within 1 hour. Non-Fickian diffusion was determined for both hydrogels.

Water and Antimicrobial Agent Permation of PU and PHEIMA Membranes in Relation to their Surface and Bulk Properties

Four types of polyurethane (PU) and two types of 2-polyhydroxyethylmethacrylate (PHEMA) membranes were prepared by convenient methods. Surface properties, water and antibacterial agent permeabilities of PU membranes were investigated. Water permeability values were determined in the region of 2000 g/m2 * 24 h. The membranes were found to have sufficient permeability toward antibacterial agents of 1% Silver Sulfadiazine and Bacitracin 10,000 UI-Neomycin sulphate 100 mg ointment.

Lipase release through semi-interpenetrating polymer network hydrogels based on chitosan, acrylamide, and citraconic acid

Abstract In this study, a series of semi-interpenetrating polymer network (IPN) hydrogels were prepared as a support material for lipase immobilization. Hydrogels were synthesized via free radical polymerization in different compositions of chitosan (Cs), acrylamide (AAm), and citraconic acid (CA). The swelling values of the hydrogels were found to be 240–400%. Depending on the swelling results, Cs–P(AAm-co-CA)-2 hydrogel was chosen for lipase immobilization. Three different types of immobilization technique were carried out. Lipase release behaviors were investigated, and immobilization yields of three immobilization methods were compared, and the maximum immobilization yield value was determined for entrapment method.