Murat Şen

A review on the radiation synthesis of copolymeric hydrogels for adsorption and separation purposes

Recent theoretical and experimental work on the radiation synthesis, characterization and the use of hydrogels containing diprotic acid moieties have been reviewed. It is shown that upon incorporating vinyl monomers carrying diprotic acid groups randomly in the main chain, non-ionic hydrogels like poly(acryl amide) and poly(n-vinyl 2-pyrrolidone) acquired stimuli-responsive behaviours. The swelling behaviours of these hydrogels are shown to be predictable reliably under varying solution conditions by a theoretical expression derived recently. Examples are given for the utilization of these hydrogels in the adsorption and separation of biomolecules, dyes and metal ions in aqueous media and their ability to release drugs in stepwise manner in response to pH of the environment.

Preparation and characterization of poly(n-vinyl 2-pyrrolidone) hydrogels

Abstract Hydrogels in the form of rods were prepared from the ternary systems n -vinyl 2-pyrrolidone/crosslinking agent/water, in composition ranges where the three components were completely miscible. Gelation was achieved by irradiating the systems with γ rays at ambient temperature. The incorporation of water into the binary system of monomer/crosslinking agent reduced the gelation dose 120-fold. The influence of dose, functionality of the crosslinking agent, and relative amounts of crosslinking agent and water on the swelling properties, diffusion behaviour of water and mechanical properties of the hydrogels were investigated. Hydrogels with swelling capabilities in the range 140–420% were obtained with tensile strength values between 0.721 and 2.717 MN m −2 .

Intravesical cationic nanoparticles of chitosan and polycaprolactone for the delivery of Mitomycin C to bladder tumors

Cationic nanoparticles of chitosan (CS), poly-epsilon-caprolactone coated with chitosan (CS-PCL) and poly-epsilon-caprolactone coated with poly-L-lysine (PLL-PCL) were developed to encapsulate intravesical chemotherapeutic agent Mitomycin C (MMC) for longer residence time, higher local drug concentration and prevention of drug loss during bladder discharge. Nanoparticle diameters varied between 180 and 340 nm depending on polymer used for preparation and coating. Zeta potential values demonstrated positive charge expected from cationic nanoparticles. MMC encapsulation efficiency depended on hydrophilicity of polymers since MMC is water-soluble. Encapsulation was increased by 2-fold for CS-PCL and 3-fold for PLL-PCL as a consequence of hydrophilic coating. Complete drug release was obtained with only CS-PCL nanoparticles. On the other hand, CS and PLL-PCL nanoparticles did not completely liberate MMC due to strong polymer-drug interactions which were elucidated with DSC studies. As far as cellular interaction was concerned, CS-PCL was the most efficient formulation for uptake of fluorescent markers Nile Red and Rhodamine123 incorporated into nanoparticles. Especially, CS-PCL nanoparticles loaded with Rhodamine123 sharing hydrophilic properties with MMC were selectively incorporated by bladder cancer cell line, but not by normal bladder epithelial cells. CS-PCL nanoparticles seem to be promising for MMC delivery with respect to anticancer efficacy tested against MB49 bladder carcinoma cell line.

Direct Formation of Nanospheres from Amphiphilic β-Cyclodextrin Inclusion Complexes

AbstractPurpose. The aim of this work was to develop and characterize a highly loaded nanoparticulate system based on amphiphilic β-cyclodextrins (CDs) to facilitate the parenteral administration of poorly soluble antifungal model drugs bifonazole and clotrimazole. Methods. Inclusion complexes were characterized with spectroscopic techniques. Particle size distribution of nanospheres were determined by photon correlation spectroscopy (PCS). Nanospheres were assessed for hemolytic activity. Entrapped and released drug quantities were determined and minimum inhibitory concentration (MIC) values of drugs, amphiphilic β-CDs, and drug loaded nanospheres were evaluated. Results. 1:1 inclusion complexes of model drugs with amphiphilic β-CDs gave nanospheres <300 nm (polydispersity index < 0.15) by nanoprecipitation technique without using surfactants. By direct preparation from preformed inclusion complexes, loading was increased 2- to 8-fold depending on CD type and loading technique. Conventionally loaded CD nanospheres displayed immediate release whereas preloaded and highly loaded nanospheres liberated model drugs over a period of 1 h reducing the initial burst effect. MIC values of bifonazole and clotrimazole were lowered significantly when associated to amphiphilic β-CD nanospheres. Conclusion. Amphiphilic β-CDs form nonsurfactant, highly loaded nanospheres with lower hemolytic activity than that of natural CDs directly from inclusion complexes. They enhanced solubility and subsequently therapeutic efficacy of the model drugs.

Controlled release of terbinafine hydrochloride from pH sensitive poly(acrylamide/maleic acid) hydrogels.

Adsorption and controlled release of terbinafine hydrochloride (TER-HCl) to and from pH sensitive poly(acrylamide/maleic acid) (P(AAm/MA)) hydrogels were investigated. P(AAm/MA) hydrogels were prepared by irradiating the ternary mixtures of AAm/MA/and water by gamma-rays at ambient temperature. Antifungal drug, TER-HCl containing hydrogels, at different drug to polymer ratios, was prepared by direct adsorption method. The influence of MA content in the gel on the adsorption capacities of hydrogel and the effect of pH on the releasing behavior of TER-HCl from gel matrix were investigated. Terbinafine adsorption capacity of hydrogels are found to increase from 2 to 38 mg TER-HCl per g dry gel with increasing amount of MA in the gel system. In vitro drug release studies in different buffer solutions show that the basic parameters affecting the drug release behavior of hydrogel are the pH of the solution and MA content of hydrogel.

Prediction of swelling behaviour of hydrogels containing diprotic acid moieties

Abstract Prediction of swelling behaviour of hydrogels containing diprotic acid moieties, sensitive to pH and ionic strenght changes of the swelling medium, was investigated. The equations derived for the prediction of the theoretical swelling curves are based on the phantom network theory of Erman et al. and the approaches of Peppas et al. For all predictions, a number of polymer-based parameters, solution property parameters and polymer-solvent combination type parameters were evaluated typical of dicarboxylated copolymers. The advantages of the derived equations for the determinations of average molecular weight between the cross-links and also a polymer-solvent interaction parameter have been exemplified.

The effect of external stimuli on the equilibrium swelling properties of poly(N-vinyl 2-pyrrolidone/itaconic acid) poly-electrolyte hydrogels

Hydrogels with varying crosslink densities and ionic moieties were prepared from the ternary systems N-vinyl 2-pyrrolidone/itaconic acid/water by irradiation with γ rays at ambient temperature. The influence of external stimuli such as pH, temperature and ionic strength of the swelling media and the type of buffer on the equilibrium swelling properties were investigated. Hydrogels showed typical pH response and temperature responses, such as high-pH and low-temperature swelling and low-pH and high-temperature deswelling. A change in the ionic strength of the swelling solution from 0.01 to 0.20 caused a decrease in the equilibrium degree of swelling of hydrogels. Oscillatory swelling behaviour was also observed and investigated in response to changes in the pH of the solution.

Non-surfactant nanospheres of progesterone inclusion complexes with amphiphilic β-cyclodextrins

Amphiphilic beta-cyclodextrins were formulated as nanospheres and characterised by particle size, zeta potential and TEM following freeze-fracture. The nanospheres were loaded with progesterone with different loading techniques involving the spontaneous formation of nanospheres from pre-formed inclusion complexes of amphiphilic beta-cyclodextrins modified on the primary or secondary face with progesterone. Inclusion complexes were characterised with various techniques including Differential Scanning Calorimetry (DSC), Fast Atom Bombardment Mass Spectrometry (FAB MS) and 1H NMR spectroscopy; and progesterone was believed to be partially included in the CD cavity. Loading properties of conventionally-loaded nanospheres were compared with those prepared directly from pre-formed inclusion complexes and loading technique was found to enhance associated drug percentage significantly (P<0.05). Although both amphiphilic beta-cyclodextrins (6-N-CAPRO-beta-CD and beta-CDC6) were capable of high progesterone loading, beta-CDC6 displayed slightly higher entrapment efficiency due to the possible higher affinity of progesterone to the 14 alkyl chains surrounding this molecule resulting in higher drug adsorption to particle surface. Progesterone was released within a period of 1 h from all formulations. Progesterone-loaded amphiphilic beta-CD nanospheres were proved to be a promising non-surfactant injectable delivery system providing high-quantity of water-insoluble progesterone rapidly within 1 h.

Investigation of Heavy Metal Ion Adsorption Characteristics of Poly(N,N Dimethylamino Ethylmethacrylate) Hydrogels

Abstract In this study, Poly(N,N dimethyl‐amino ethylmethacrylate) (Poly(DMAEMA)) hydrogels with varying compositions were prepared in the form of rods by irradiating ternary mixtures of N,N‐dimethylamino ethylmethacrylate/ethyleneglycoldimethacrylate/water with gamma rays at ambient temperature. Swelling studies of poly (DMAEMA) hydrogels were performed at different pH values and maximum swelling values reached at pH 2. The adsorption characteristics of Pb(II), Cd(II), Ni(II), Zn(II), Cu(II), and Co(II) ions to poly(N,N dimethylamino ethylmethacrylate) hydrogels were investigated by a batch process. The order of affinity based on amount of metal ion uptake was found as follows: Cu(II)>Zn(II)≅Co(II)>Pb(II) >> Ni(II)>Cd(II). In the adsorption studies of Cu(II), Zn(II), Co(II), Pb(II), Ni(II), and Cd(II) ions the Langmuir type adsorption isotherms were observed for all gel systems.

Radiation synthesis of poly(N-vinyl 2-pyrrolidone/itaconic acid) hydrogels and their controlled release behaviours

Abstract N-vinyl 2-pyrrolidone/itaconic acid copolymeric hydrogels were prepared by irradiating the ternary mixtures of N -vinyl 2-pyrrolidone/itaconic acid/water by γ-rays at ambient temperature. For the characterization of network structure of these hydrogels, swelling properties in phosphate buffer solutions and molecular weight between crosslinks were investigated. Methylene Blue was used as a model drug for the investigation of controlled release behaviour of hydrogels. Specific Methylene Blue adsorption capacity of hydrogels are found to increase from 0.36 to 47.7 (mg MB/g gel) with increasing amount of itaconic acid in the gel system. The influence of molecular weight between cross-links, the concentration of ionizable groups, ionization and concentration of MB in the hydrogel were examined. The release studies show that one of the basic parameters affecting the drug release behaviour of hydrogels is the pH of the solution.