Reduction-sensitive amphiphilic triblock copolymers self-assemble into stimuli-responsive micelles for drug delivery.

Polymeric nanostructures obtained through self-assembly of reduction-sensitive amphiphilic triblock copolymers were investigated as potential drug delivery systems. The characteristic feature of these polymers is their cleavable disulfide bond in the center of the hydrophobic block. Therefore, the triblock copolymers can be cleaved into amphiphilic diblock copolymers. A poly(2-hydroxyethyl methacrylate)-b-poly(butyl methacrylate)-S-S-poly(butyl methacrylate)-b-poly(2-hydroxyethyl methacrylate) (PHEMA-b-(PBMA-S-S-PBMA)-b-PHEMA) triblock copolymer was synthesized. It self-assembled into micelles which were used to encapsulate hydrophobic dye molecules (Nile Red, BodiPy 630/650) as model payloads. The self-assembled nanostructures disintegrated upon reduction of the disulfide bond, releasing their cargo and yielding larger particles that formed aggregates in solution after 24 h. A burst release of payload was shown within the first 15 min, followed by a constant release over several hours. As concentration gradients of reducing agents are commonly found in biological systems, the micelles could be used as redox-sensitive nanocarriers for the intracellular delivery of drugs.

Self-organization behavior of methacrylate-based amphiphilic di- and triblock copolymers.

Amphiphilic di- and triblock copolymers having different hydrophilic-to-hydrophobic block length ratio were synthesized using ATRP. The self-assembly behavior of these AB and ABA block copolymers consisting of poly(n-butyl methacrylate) (B) and poly(2,2-(dimethylaminoethyl methacrylate) (A) was investigated using a combination of dynamic light scattering, negative-stain transmission electron microscopy, cryoelectron microscopy, and atomic force microscopy. Two populations of self-organized structures in aqueous solution, micelles and compound micelles, were detected for diblock copolymers. Triblock copolymers assembled into vesicular structures of uniform sizes. Furthermore it was found that these vesicles tended to compensate the high curvature by additional organization of the polymer chains outside of the membrane. The chain hydrophilicity of the polymers appeared to have a critical impact on the self-assembly response toward temperature change. The self-reorganization of the polymers at different temperatures is discussed.

CO-alkene polymers are biocompatible scaffolds for primary urothelial cells in vitro and in vivo.

OBJECTIVE: To investigate CO-alkene polymers, novel synthetic nonbiodegradable polymers, as a potential biomaterial for urological applications. MATERIALS AND METHODS: Porcine urothelial cells were seeded on cover glasses (96 wells; 10 000 cells/well) coated with CO-alkene polymers [propylene/N-Acetyl-O'-(hex-5-enyl)-l-tyrosine ethyl ester/CO (PTCO) and hexene-CO (HxCO)]. The following conditions were investigated: cells seeded; (i) on PTCO, (ii) on HxCO, (iii) in PTCO-conditioned medium, (iv) in HxCO-conditioned medium, (v) on glass without polymers, (vi) on polystyrene, and (vii) on polystyrene treated with 1.25% NaCl (toxic control). Cell counts, cell death detection assay, and a cell activity assay (XTT, a tetrazolium-based colorimetric assay) were performed after 3, 6 and 9 days. Urothelial-cell seeded-PTCO films (0.5 x 10(6) cells/cm(2)) were implanted into the subcutaneous space of athymic mice for up to 12 weeks and unseeded PTCO polymers were implanted as a negative control. RESULTS: The urothelial cell adherence rates on the polymers were similar to those for glass and polystyrene. The cell activity (XTT assay) was higher in cells seeded on the polymers than in cells seeded on polystyrene and glass after 3 and 6 days. There were no significant differences between the apoptosis rates of all groups at the given sample times, except for the high levels in the toxic control. In vivo the urothelial cells survived on the polymers for 12 weeks with no adverse reactions in any of the mice. CONCLUSIONS: CO-alkene polymers are biocompatible materials for urothelial cells in vitro and in vivo, and thus are potential biomaterials for the urogenital tract.

Synthesis of functional poly(1,4-ketone)s bearing bioactive moieties by Pd-catalyzed insertion polymerization.

The synthesis of novel alternating polyketones bearing pendent bioactive moieties is presented. These materials were prepared by palladium catalyzed coordination polymerization of carbon monoxide and alpha-olefins substituted with protected tyrosine or with dipeptide sequences such as tyrosine-glycine, tyrosine-alanine, and tyrosine-valine. Copolymerization experiments of CO with monomers containing vitamin E or testosterone were also successfully performed under mild reaction conditions. The dicationic Pd (II) bis(phoshine) complex [Pd(dppp)(NCCH(3))(2)](BF(4))(2) was used as catalyst precursor giving rise to macromolecules with well-defined structures.