The synthesis of polymer nano hydrogels using pulsed electron beams

Complete text of publication follows. Nano-hydrogels made of bio-compatible hydrophilic polymers can be used in various medical applications such as drug delivery and imaging. Intravenously introduced hydrogel-drug conjugate (10 - 200 nm particles can be effectively accumulated in tissues/organs by prolonged circulation and can be selectively transported into tumor tissues by the EPR (enhanced permeability and retention) effect. We are investigating the radiation-induced synthesis of functionalized polymer nano-hydrogels that can serve as targeted nano-medicine carriers. The latest results on the synthesis and kinetic analysis of poly(vinyl pyrrolidone) (PVP) nanogels in dilute aqueous solutions using rays and electron beams, particularly at high temperature, will be presented. At temperatures above 60 deg C, PVP chains start to collapse decreasing its average hydrodynamic radius, Rh from 23 (at 20 deg C) to 15.6 nm (at 80 deg C) due to the disruption of polymer-water hydrogen bonds. The collapsed form of the PVP molecules enhances the intra-crosslinking reactions of the radiolytically produced free radicals leading to a further decrease in its average Rh to the value of 14 nm (γ-ray irradiation with 10 kGy). The nano-gel structure was also synthesized using pulsed electron beam irradiation at high repetition rates, which give rise to a high intra-chain yield of multiple free radicals. These free radicals enhance the intra-crosslinking reactions leading to the formation of smaller size nanogel molecules with average Rh value of 12 nm at 300 pulses per second. At high pulse repetition rates, the intramolecular crosslinking reactions of the carbon centered free radicals are preferred; this effect is enhanced at higher temperatures. While the high dose rate pulses enhance the intra-molecular crosslinking, low dose rate pulses and the extended shape of the PVP molecules favor inter-molecular crosslinking. From the pulse radiolysis, the second order reaction rate constants (2k) of PVP radical recombination are determined are 1.1 - 2.8 x 109 L mol-1 s-1 [(PVP-H)· ε390nm = 510 ± 30 L mol-1 cm-1] The activation energy (Ea) of this reaction is calculated from the Arrhenius plot of PVP radical decay rate constants at a series of temperatures and have a value of ca. 1.0 (below 60 deg C) and 6.8 kcal mol-1 (above 60 deg C). Two Ea can be explained by the different rate-determining mechanisms of PVP radical recombination reaction at the two temperature regions. Low Ea (at below 60 deg C) reflects the diffusion controlled polymer radical reaction in good solvent. But higher temperature above 60 deg C, polymer chains are segregated from the aqueous solution by micro-phase separation and collapse. The movement of the polymer radical chain is limited largely to within the region in which it is almost solid in character and so Ea for radical recombination at high temperature is higher than that obtained for lower temperature. The Rh of radiolytically produced hydrogel nanoparticles were measured by means of the dynamic light scattering (DLS) experiments.