Tricarbonyl-rhenium complexes of a thiol-functionalized amphoteric poly(amidoamine).

An amphoteric thiol-functionalized poly(amidoamine) nicknamed ISA23SH(10%) was synthesized. Rhenium complexes 1 and 2, containing 0.5 and 0.8 equiv of rhenium, respectively, were easily obtained by reacting ISA23SH(10%) with [Re(CO)(3)(H(2)O)(3)](CF(3)SO(3)) in aqueous solution at pH 5.5. Both ISA23SH(10%), and its rhenium complexes were soluble in water under physiological conditions. The resultant solutions were stable, even in the presence of cysteine. Rhenium chelation occurred through the S and N atoms of the cysteamine moiety, as demonstrated by (1)H, (13)C, and (15)N NMR spectroscopy. The diffusion coefficients and the hydrodynamic radii of ISA23SH(10%) and complex 1 were determined by pulsed gradient spin echo (PGSE) NMR experiments. The radius of the rhenium complexes 1 and 2 was always slightly larger than that of the parent polymer. TEM analysis showed that both complexes form spherical nanoparticles with narrow size distributions. Consistent results were obtained by dynamic light scattering. The observed sizes were in good agreement with those evaluated by PGSE. Preliminary in vitro and in vivo biological studies have been performed on complexes 1 and 2 as well as on the parent ISA23SH(10%). Neither hemolytic activity of the two rhenium complexes and the parent polymer, up to a concentration of 5 mg/mL, nor cytotoxic effects were observed on Hela cell after 48 h at a concentration of 100 ng/mL. In vivo toxicological tests showed that ISA23SH(10%) is highly biocompatible, with a maximum tolerated dose (MTD) of 500 mg/kg. No toxic side effects were apparent after the intravenous injection in mice of the two rhenium complexes in doses up to 20 mg/kg.

Enhanced antiviral activity of acyclovir loaded into nanoparticles.

The activity of antivirals can be enhanced by their incorporation in nanoparticulate delivery systems. Peculiar polymeric nanoparticles, based on a ß-cyclodextrin-poly(4-acryloylmorpholine) monoconjugate (ß-CD-PACM), are proposed as acyclovir carriers. The experimental procedure necessary to obtain the acyclovir-loaded nanoparticles using the solvent displacement preparation method will be described in this chapter. Fluorescent labeled nanoparticles are prepared using the same method for cellular trafficking studies. The biocompatibility assays necessary to obtain safe nanoparticles are reported. Section 4 of this chapter describes the assessment of the antiviral activity of the acyclovir-loaded nanoparticles.

Heat enhances gas delivery and acoustic attenuation in CO(2) filled microbubbles.

Thermo-responsive chitosan microbubbles were developed as new therapeutic device for vehiculating gases to tissues concomitantly to hyperthermic treatments. Aiming at applications to non-invasive temperature monitoring, microbubbles were characterized for acoustic attenuation properties in the 1-15 MHz range both by direct methods and by B-mode Ultrasound imaging up to 43 degrees C, which is the temperature used in clinical hyperthermia. The chitosan microbubbles showed a mean diameter of 1 microm at room temperature, which slightly decreases after heating, enhancing gas delivery. Acoustic attenuation monotonically increases with temperature, being the extent of such variation larger than that observed in tissues. Both the physico-chemical and the acoustic profiles showed reversible variations of microbubbles approaching 43 degrees C, which might be of interest for applications in hyperthermic therapies.