Mario Carenza

Recent achievements in the use of radiation polymerization and grafting for biomedical applications

Abstract Papers mainly published in the last few years on radiation processing of polymeric systems for biomedical applications carried out in different laboratories are reviewed. Radiation-induced polymerization to obtain hydrogels as carriers for immobilization of bioactive agents and for controlled release of drugs is described. Radiation modification of polymers by graft copolymerization and/or crosslinking for the same purposes is also reported. The second part of the paper deals with the work recently carried out in the authors laboratory. Radiation-induced polymerization at low temperatures to obtain matrices susceptible to entrap drugs, including peptides and proteins, is discussed. Radiation grafting of hydrophilic monomers onto relatively new inorganic polymers, i.e. polyphosphazenes, and the properties of such modified polymeric materials, together with their biocompatibility, are summarized.

THE STATE OF WATER IN THERMORESPONSIVE POLY(ACRYLOYL-L-PROLINE METHYL ESTER) HYDROGELS OBSERVED BY DSC AND 1H-NMR RELAXOMETRY

Hydrogels that reversibly swell or shrink in water with decreasing or increasing temperature, respectively, were obtained by γ ray-induced polymerization of acryloyl-l-proline methyl ester in the presence of different amounts of a crosslinking agent. The role of water in the hydrated polymers was investigated by DSC and 1H-NMR relaxometry. From the curves of fusion of water determined by the former it was possible to ascertain that the amount of both freezing and non freezing water decreased with increasing the crosslinker percentage and/or swelling temperature. Moreover, at the temperatures higher than 37°C, the water absorbed by the different hydrogels is mostly present as non freezing water. The 1H-NMR relaxometry study enabled the spin–spin and spin–lattice relaxation curves to be analyzed. It was possible to distinguish three “populations” of protons and identify two of them with protons of freezing and non freezing water determined by DCS.

Pulse radiolysis of methacryloyl-l-proline methyl ester in dilute aqueous solution

ABSTRACT The reactions of hydroxyl radical, hydrogen atom and hydrated electron intermediates of water radiolysis with a hydrogel-forming monomer, methacryloyl-L-proline methyl ester (MA-ProOMe), were studied by pulse radiolysis in dilute aqueous solutions and compared with the reactions of the acrylic derivative (A-ProOMe). The spectral and kinetic characteristics of the first step of OH, H and eaq- reactions with the two monomers are very similar. There are considerable differences in the next steps. In neutral solutions, the electron adduct of A-ProOMe decays in slow radical-radical reactions. The adduct of MA-ProOMe, however undergoes a fast irreversible protonation resulting in α-carboxyalkyl radical. The oligomerization reactions occurring in MA-ProOMe solutions are slow, and under adopted pulse radiolytic conditions, they are observable only at high monomer concentrations. In A-ProOMe solutions the reaction is significantly faster.

Hydrogels obtained by radiation-induced polymerization as delivery systems for peptide and protein drugs

Abstract The controlled release of peptides and proteins from hydrogels obtained by radiation-induced polymerization of 2-hydroxyethyl methacrylate at a low temperature was studied. It was found that the extent of release progressively decreased as protein molecular weight increased until no further release occurred above a critical value of the latter. However, an increasing rate of protein release was found if the polymerization was carried out in the presence of poly(ethylene glycol), PEG. Moreover, only with high molecular weight PEGs were large proteins released. The release data as a function of swellability and porosity of polymer matrices were discussed.

Poly (acryloyl-l-proline methyl ester) hydrogels obtained by radiation polymerization for the controlled release of drugs

Abstract Thermosensitive hydrogels were obtained by radiation-induced polymerization of acryloyl- l -proline methyl ester in the presence of a crosslinking agent. The measurements of equilibrium water content in the temperature range between 0° and 60°C showed that the samples swelled at low temperatures while they shrank at high temperatures. These hydrogels were used as drug delivery systems for the controlled release of insulin. In vivo studies carried out on diabetic rats ascertained a significant reduction in the hyperglycemic level in the blood which continued for about 2 months.

Thermally reversible gels based on acryloyl-L-proline methyl ester as drug delivery systems

Abstract Thermally reversible hydrogels were synthesized by radiation-induced copolymerization of acryloyl- l -proline methyl ester with hydrophilic or hydrophobic monomers. The swelling behaviour was found to be affected by a proper balance of the latter. In particular, the transition temperature of the different hydrogels shifted to higher or lower values depending on the presence of hydrophilic or hydrophobic moieties in the polymer chain, respectively. Acetaminophen, an analgesic and antipyretic drug, was entrapped into some hydrogels and a wide range of release rates was obtained according to the nature of the comonomers. A novel thermoresponsive hydrogel was also prepared by radiation polymerization of acryloyl- l -proline methyl ester in the presence of 4-acryloyloxy acetanilide, an acrylic derivative of acetaminophen. Again, the swelling curves showed an inverse function of temperature. It was shown that with this hydrogel bearing the drug covalently attached to the polymer backbone, the hydrolysis process was the rate-determining process of the drug release.

Intelligent drug delivery systems obtained by radiation

Radiation-induced polymerization of acryloyl-L-proline methyl ester, an α-aminoacid-containing monomer, in the presence of a crosslinking agent and a hydrophilic monomer gave rise to polymer hydrogels whose water content at equilibrium was found to decrease as the swelling temperature increased. Some hydrogel samples were obtained with entrapped acetaminophen, an analgesic and antipyretic drug. It was ascertained that the release of the drug was controlled by both the hydrophilicity of the polymer matrices and the environmental temperature.

Hydrogels obtained by radiation-induced polymerization for yeast cells immobilization

Abstract Radiation-induced polymerizations of several acrylic and methacrylic esters at both room temperature and low temperature were carried out. The polymer matrices obtained under the latter conditions were examined as carriers for immobilization of yeast cells. The adhesion of the latter was found to be markedly influenced by both matrix hydrophilicity, determined by equilibrium water content measurements, and porosity, evaluated by optical microscopy and scanning electron microscopy. The ethanol productivity during batch fermentation as a function of these parameters is discussed.

Immobilization of yeast cells on hydrogel carriers obtained by radiation-induced polymerization

Abstract Polymer hydrogels were obtained by radiation-induced copolymerization at -78°C of aqueous solutions of acrylic and methacrylic esters. The matrices were characterized by equilibrium water content measurements, by optical microscopy observations and by scanning electron microscopy analysis. Yeast cells were immobilized on these hydrogels and the ethanol productivity by batch fermentation was determined. Matrix hydrophilicity and porosity were found to deeply influence the adhesion of yeast cells and, hence, the ethanol productivity. The latter as well as other physico-chemical properties were also affected by the presence of a crosslinking agent added in small amounts to the polymerizing mixture.

Activity dependence of immobilized yeast cells on the various natures of polymer carriers for immobilization produced with radiation polymerization at low temperatures

Abstract Yeast cells were immobilized with physical adsorption and multiplication method using kinds of polymer carriers produced with radiation polymerization at low temperatures. Dependence of activity of immobilized yeast cells was investigated on the some natures of polymer carriers such as hydrophilicity, water content, swellability, morphological factors observed with scanning electron microphotographic technique.