Piotr Ulanski

Synthesis of hydrogels by irradiation of polymers in aqueous solution

Abstract Radiation methods used to obtain hydrogels for biomedical applications are briefly discussed. The method based on the irradiation of polymers in aqueous solution is dealt with in some detail. The importance of basic studies on the involved processes is emphasized. Some aspects of the radiation chemistry of polymers in aqueous solutions are discussed (e.g. the factors influencing the competition between the intermolecular crosslinking and other reactions), basing mainly on the data obtained by the authors’ research group.

Radiation formation of hydrogels for biomedical purposes. Some remarks and comments

Abstract Formation of hydrogels by means of radiation technique is described and some differences connected with irradiation in solid state and solution are pointed out. Structures of primary macroeradicals of some hydrophillic polymers are given. Examples of applications of hydrogels as drug delivery systems, implants, injectable systems, stimuli-responsive systems, hybrid-type organs as well as general requirements for such systems are reviewed. Hydrogel wound dressings produced by radiation technology and marketed in the Central Europe are described.

Radiation formation of polymeric nanogels

Abstract An alternative method of synthesis of polymeric nanogels is proposed, based not on polymerization, but on intramolecular crosslinking of polymer chains, initiated by pulse irradiation in dilute aqueous solutions. Kinetic data show that for many water-soluble polymers irradiation under these conditions result in intramolecular crosslinking. Preliminary product studies on poly(vinyl alcohol) indicate that in fact internally crosslinked macromolecules can be obtained by this technique.

Synthesis of poly(acrylic acid) nanogels by preparative pulse radiolysis

Abstract Nanogels are sub-micron size, water-swellable crosslinked structures of hydrophilic polymers. In this work a radiation-based synthesis method that has been previously tested for neutral polymers is applied for production of nanogels of a synthetic polyelectrolyte—poly(acrylic acid) (PAA). In this technique dilute, deoxygenated PAA solution (pH 2) circulating in a closed loop is subjected to pulse irradiation with fast electrons. In each pulse many tens of radicals are instantaneously formed on every macromolecule. One of the major reaction paths of these radicals is intramolecular recombination leading to the formation of nanogels. It is demonstrated that radiation-induced reactions in our system show a typical feature of intramolecular crosslinking, i.e . a strong decrease in dimensions of a polymer coil without an accompanying decrease in molecular weight. In accordance with expectations based on earlier observations on non-polar polymers, intramolecular recombination of PAA-derived radicals proceeds according to non-classical kinetics. A model of non-homogeneous kinetics with time-dependent rate constant has been applied to describe this behaviour and the relationship between kinetic parameters and initial average number of radicals per chain is briefly discussed. The weight-average molecular weight of the products is influenced by side reactions, mainly degradation (chain breakage) and intermolecular crosslinking.

THE USE OF RADIATION TECHNIQUE IN THE SYNTHESIS OF POLYMERIC NANOGELS

Abstract Irradiation of dilute, deoxygenated aqueous solutions of hydrophilic polymers with high-dose pulses of fast electrons leads to the simultaneous formation of many radicals on each polymer chain. These radicals undergo mainly intramolecular recombination. In this way internally crosslinked macromolecules – nanogels – are formed. Current data on poly(vinyl pyrrolidone) show that during this process the weight-average molecular weight remains almost constant, but there is a pronounced decrease in the radius of gyration of macromolecules, an effect expected for the formation of compact, internally crosslinked structures.

Nano-, micro- and macroscopic hydrogels synthesized by radiation technique

Radiation techniques, due to the additive-free initiation and easy process control, are very suitable tools for synthesis of biomaterials, especially hydrogels. In our group, a number of techniques have been elaborated allowing for targeted synthesis of gels of various size ranges, from internally crosslinked individual macromolecules, via microgels to macroscopic hydrogels. An example of a mature technology of this kind are hydrogel wound dressings, being now produced on large scale in Poland and other countries. Current research projects include: hydrogel-based system for anticancer therapy due to local drug delivery, systems for encapsulation of living cells, new approach to the synthesis of polymeric material for intervertebral discs implant, temperature-sensitive membranes, hydrogel phantoms of 3D radiation dosimeter for radiotherapy, degradation-resistant nanogels and microgels for biomedical purposes (e.g. synovial fluid substitute), hydrogel-based dietary products and adjustment of the molecular weight of biopolymers.

Pulse radiolysis in model studies toward radiation processing

Abstract Using the pulse radiolysis technique, the OH-radical-induced reactions of poly(vinyl alcohol) PVAL, poly(acrylic acid) PAA, poly(methacrylic acid) PMA, and hyaluronic acid have been investigated in dilute aqueous solution. The reactions of the free-radical intermediates were followed by UV-spectroscopy and low-angle laser light-scattering; the scission of the charged polymers was also monitored by conductometry. For more detailed product studies, model systems such as 2,4-dihydroxypentane (for PVAL) and 2,4-dimethyl glutaric acid (for PAA) was also investigated. With PVA, OH-radicals react predominantly by abstraction of an H-atom in α-position to the hydroxyl group (70%). The observed bimolecular decay rate constant of the PVAL-radicals decreases with time. This has been interpreted as being due to an initially fast decay of proximate radicals and a decrease of the probability of such encounters with time. Intramolecular crosslinking (loop formation) predominates at high doses per pulse. In the presence of O2, peroxyl radicals are formed which in the case of the α-hydroxyperoxyl radicals can eliminate HO2-radicals in competition with bimolecular decay processes which lead to a fragmentation of the polymer. In PAA, radicals both in α-position (characterized by an absorption near 300 nm) and in β-position to the carboxylate groups are formed in an approximately 1:2 ratio. The lifetime of the radicals increases with increasing electrolytic dissociation of the polymer. The β-radicals undergo a slow (intra- as well as intermolecular) H-abstraction yielding α-radicals, in competition to crosslinking and scission reactions. In PMA only β-radicals are formed. Their fragmentation has been followed by conductometry. In hyaluronic acid, considerable fragmeentation is observed even in the absence of oxygen which, in fact, has some protective effect against this process. Thus free-radical attack on this important biopolymer makes it especially vulnerable with respect to a reduction of its viscosity, and in rheumatic diseases this effect may be the reason for their painfulnes.

Hydrogels for biomedical purposes

Abstract Medical advances that have prolonged the average life span have generated more needs for new materials that can be used as tissue and organ replacements, drug delivery systems or components of devices related to therapy and diagnosis. One of the most promising class of such materials seems to be hydrogels. Taking poly(ethylene oxide) — PEO as an example of hydrogel-forming polymers the mechanism of formation and decay of its macroradical in aqueous solution was discussed. The influence of scavengers as well as concentration of PEO solution on the formation of gel has been shown. Short description of technologies of some hydrogel biomaterials obtained by means of radiation technique was given.

Radiation-induced degradation and crosslinking of poly(ethylene oxide) in solid state

The effects of g-irradiation on solid poly(ethylene oxide) (PEO) of an initial weight-average molecular weight of 6.3.105 Da were investigated by gel permeation chromatography and viscometry. The parameters studied were changes in number- and weight-average molecular weight, molecular weight distribution and viscosity of PEO in aqueous solution. Irradiation of poly(ethylene oxide) powder in the presence of oxygen leads to the dominance of chain scission reactions. Their high radiation-chemical yield [G(scission) » 2.5.10-6 mol/J] indicates the occurrence of effective chain reactions. Upon irradiation in vacuum, crosslinking and scission occur side-by-side and the changes in molecular weight are less pronounced in the studied dose range (up to 20 kGy). Scission dominates for doses up to ca. 15 kGy, while for higher doses intermolecular crosslinking gains in importance. The competition between these processes seems to depend not only on the applied dose but also to be influenced by the inhomogenity of the material (molecular weight and/or possibly the crystallinity). Parallel occurrence of scission and crosslinking leads to the broadening of the molecular weight distribution.

Pulse radiolysis of poly(ethylene oxide) in aqueous solution. II. Decay of macroradicals

Abstract Pulse radiolysis studies on the decay of macroradicals derived from poly(ethylene oxide) in deaerated aqueous solution have shown that this process does not follow classical second-order kinetics. This is attributed to the nature of the dominating reaction, i.e. intramolecular recombination. The rate of decay depends mainly on the average initial number of radicals formed on one chain (ZRO). It is shown that the decay may be well described with the non-homogeneous kinetics with time-dependent rate constant in the form k = B tα-1. The influence of polymer concentration, molecular weight and ZRO on the parameter α (a measure of non-homogeneity) is discussed.