Sang Cheon Lee

Polymeric micelles of poly(2-ethyl-2-oxazoline)-block-poly(ε-caprolactone) copolymer as a carrier for paclitaxel

Abstract Polymeric micelles based on amphiphilic block copolymers of poly(2-ethyl-2-oxazoline) (PEtOz) and poly(e-caprolactone) (PCL) were prepared in an aqueous phase. The loading of paclitaxel into PEtOz–PCL micelles was confirmed by 1 H-NMR spectra. Paclitaxel was efficiently loaded into PEtOz–PCL micelles using dialysis method, and the loading content of paclitaxel in micelles was in the range 0.5–7.6 wt.% depending on the block composition of block copolymers, organic solvent used in the dialysis, and feed weight ratio of paclitaxel to block copolymer. The higher the content of hydrophobic block in the block copolymers, the higher the loading efficiency of micelles for paclitaxel. When acetonitrile was used as solvent, a higher drug loading efficiency was obtained than with THF. The loading efficiency decreased with increasing feed weight ratio of paclitaxel to block copolymer from 0.1:1 to 0.2:1. The hydrodynamic diameters of paclitaxel-loaded micelles were in the range 18.3–23.4 nm with narrow size distribution. The hemolysis test of PEtOz–PCL performed in vitro indicated that the toxicity of PEtOz–PCLs to lipid membrane was not significant compared with Tween 80, and was comparable to that observed with Cremophore EL. The proliferation inhibition activity of paclitaxel-loaded micelles for KB human epidermoid carcinoma cells was also evaluated in vitro. Paclitaxel-entrapped polymeric micelles exhibited comparable activity to that observed with Cremophore EL-based paclitaxel formulations in inhibiting the growth of KB cells.

Phase-transition characteristics of amphiphilic poly(2-ethyl-2-oxazoline)/poly(ε-caprolactone) block copolymers in aqueous solutions

Amphiphilic diblock and triblock copolymers of various block compositions based on hydrophilic poly(2-ethyl-2-oxazoline) (PEtOz) and hydrophobic poly(e-caprolactone) were synthesized. The micelle formation of these block copolymers in aqueous media was confirmed by a fluorescence technique and dynamic light scattering. The critical micelle concentrations ranged from 35.5 to 4.6 mg/L for diblock copolymers and 4.7 to 9.0 mg/L for triblock copolymers, depending on the block composition. The phase-transition behaviors of the block copolymers in concentrated aqueous solutions were investigated. When the temperature was increased, aqueous solutions of diblock and triblock copolymers exhibited gel–sol transition and precipitation, both of which were thermally reversible. The gel–sol transition- and precipitation temperatures were manipulated by adjustment of the block composition. As the hydrophobic portion of block copolymers became higher, a larger gel region was generated. In the presence of sodium chloride, the phase transitions were shifted to a lower temperature level. Sodium thiocyanate displaced the gel region and precipitation temperatures to a higher temperature level. The low molecular weight saccharides, such as glucose and maltose, contributed to the shift of phase-transition temperatures to a lower temperature level, where glucose was more effective than maltose in lowering the gel–sol transition temperatures. The malonic acid that formed hydrogen bonds with the PEtOz shell of micelles was effective in lowering phase-transition temperatures to 1.0M, above which concentration the block copolymer solutions formed complex precipitates.

Hyperbranched poly(ether ketone) analogues with heterocyclic triazine moiety : Synthesis and peripheral functionalization

Hyperbranched poly(ether ketone) with 1,3-s-triazine moiety was prepared by a one-pot polymerization of an AB 2 type monomer, 2,4-bis(4-hydroxyphenyl)-6-(4-(4-(4-fluorobenzyl)phenoxy)phenyl)-1,3,5-s-triazine, which was synthesized from cyanuric chloride. The selective reactivity of three chlorine atoms on cyanuric chloride toward nucleophiles provides a very efficient route for the systematic synthesis of AB 2 type triazine monomers and their hyperbranched polymers. The resulting polymers exhibited a glass transition at 264°C without any indication of crystallinity. The modification of the peripheral hydroxyl groups on the hyperbranched polymers by methoxy, oligoethyleneoxy, or sterayl moieties brought about remarkablechanges in their solubility and glass transition temperatures. The amphiphilic nature of the 2-[2-(2-(2-methoxyethoxy)ethoxy)ethoxy)]ethoxy-terminated pmoly(ether ketone) analogue in an aqueous phase was investigated by using fluorescence techniques and dynamic light scattering. It was found that the analogue forms of self-aggregation at a critical aggregation concentration of 12.6 mg/L. The mean diameter of the aggregates was 320 nm. The steady-state fluorescence anisotropy value (r) of 1,6-diphenyl-1,3,5-hexatriene (DPH) in the hydrophobic domain was 0.240.

Bone morphogenic protein-2 (BMP-2) immobilized biodegradable scaffolds for bone tissue engineering

Recombinant human bone morphogenic protein-2 (rhBMP-2), which is known as one of the major local stimuli for osteogenic differentiation, was immobilized on the surface of hyaluronic acid (HA)-modified poly(ε-caprolactone) (PCL) (HA-PCL) scaffolds to improve the attachment, proliferation, and differentiation of human bone marrow stem cells (hBMSCs) for bone tissue engineering. The rhBMP-2 proteins were directly immobilized onto the HA-modified PCL scaffolds by the chemical grafting the amine groups of proteins to carboxylic acid groups of HA. The amount of covalently bounded rhBMP-2 was measured to 1.6 pg/mg (rhBMP/HA-PCL scaffold) by using a sandwich enzyme-linked immunosorbant assay. The rhBMP-2 immobilized HA-modified-PCL scaffold exhibited the good colonization, by the newly differentiated osteoblasts, with a statistically significant increase of the rhBMP-2 release and alkaline phosphatase activity as compared with the control groups both PCL and HA-PCL scaffolds. We also found enhanced mineralization and elevated osteocalcin detection for the rhBMP-2 immobilized HA-PCL scaffolds, in vitro.

A Covalently Interconnected Phosphazene-Silicate Network: Synthesis and Surface Functionalization

A sol-gel precursor was prepared by the reaction of poly[bis(2-(2-hydroxyethoxy)ethoxy)phosphazene] (1) with 3-isocyanatopropyltriethoxysilane. It was then sol-gel polymerized to produce a covalently interconnected phosphazene-silicate network with urethane functionalities. Isocyanato groups were introduced on the surface of the network through coupling by allophanate formation between hexamethylene diisocyanate and urethane functionalities on the gel surface. Heparin was immobilized on the surface of the network by reacting hydroxyl or amino groups of heparin with the surface isocyanato groups. The activity of the immobilized heparin was 4.0% that of free heparin.