Fu Xi

Synthesis and thermal properties of novel star-shaped poly(l-lactide)s with starburst PAMAM–OH dendrimer macroinitiator

Abstract The starburst PAMAM–OH dendrimer (generation 3) as macroinitiator for the synthesis of star-shaped polylactides in the presence of stannous octoate was investigated. Effects of molar ratios of monomer to initiator, monomer to catalyst, monomer conversion, and reaction temperature on polymerization were studied. It is found that 16–21 polylactide arms can be attached to the surface of dendrimer initiator, and the molecular weight of polylactides can be controlled by variation of molar ratios of monomer to initiator and polymerization time. Thermal analysis indicates that the star-shaped polylactides possess lower glass transition temperature, melting point, crystallinity, and maximum decomposition temperature than those of linear polylactide.

Supramolecular Hydrogels from Cisplatin-Loaded Block Copolymer Nanoparticles and α-Cyclodextrins with a Stepwise Delivery Property

A stepwise anticancer drug delivery system based on an injectable supramolecular hydrogel was presented. In this system, poly(ethylene glycol)-b-poly(acrylic acid) (PEG-b-PAA) block copolymer nanoparticles containing cisplatin were released by erosion of the hydrogels and then the cisplatin was released from the nanoparticles by exchanging with chloride ions. By mixing α-cyclodextrins (α-CDs) and the PEG-b-PAA micelles with their PAA cores loaded with the cisplatin in water, the novel supramolecular hydrogels were generated by threading α-CDs onto the PEG segments and forming physical cross-links of molecular necklaces. The gelation properties could be tuned by changing concentrations of the polymers and cisplatin, their feeds, and by adding PEG homopolymers or Pluronic copolymers as additives. Structures and properties of the supramolecular hydrogels containing cisplatin were studied by wide-angle X-ray diffraction (XRD) and rheology measurements, respectively. The thixotropic effect of the hydrogels and their reversible sol-gel transition were confirmed. In vitro hydrogel erosion experiments were conducted and cisplatin release in saline and pure water was quantified. Hydrogel erosion produced discrete nanoparticles from which cisplatin was released completely in saline. In contrast, the hydrogels were eroded into nanoparticles in pure water, but no cisplatin could be released. In vitro cytotoxicity studies showed that the cisplatin-loaded hydrogels inhibited the growth of human bladder carcinoma EJ cells with a similar potency as that of the free cisplatin, whereas the hydrogels without cisplatin showed no cytotoxicity. These results suggested that the cisplatin-coordinated PEG-b-PAA/α-CD supramolecular hydrogels hold great potential as an injectable system for sustained delivery of cisplatin in cancer therapy.

Supramolecular hydrogels as a universal scaffold for stepwise delivering Dox and Dox/cisplatin loaded block copolymer micelles

A general and simple method was presented for preparing supramolecular hydrogels to deliver anticancer drugs. In this system, hydrophobic anticancer drug doxorubicin (Dox) was loaded into poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) amphiphilic block copolymer micelles by hydrophobic interaction. The drug loaded micelles were then mixed with α-cyclodextrin (α-CD) solution to generate the hydrogel. The α-CDs were threaded onto the PEG coronae of the micelles, and formed physical crosslinks of the molecular necklaces. Moreover, by mixing solutions of cisplatin complexed poly(ethylene glycol)-b-poly(acrylic acid) (PEG-b-PAA) micelles, Dox loaded PEG-b-PCL micelles and α-CDs together, a dual-drug loaded supramolecular hydrogel was generated. The gelation properties could be tuned by changing concentrations and polymerization degree of the polymers, and by adding PEG homopolymers or Pluronic copolymers as additives. Structures and properties of the drug loaded hydrogels were studied by wide-angle X-ray diffraction (XRD) and rheology measurement, respectively. In vitro drug release in PBS with different pH values was quantified. The erosion of hydrogels produced discrete micelles, from which the free drugs were released. In vitro cytotoxicity studies showed that the Dox loaded hydrogel inhibited the growth of human bladder carcinoma EJ cells, and the dual-drug loaded hydrogel showed even higher cytotoxicity.

Biamphiphilic triblock copolymer micelles as a multifunctional platform for anticancer drug delivery.

Novel micelles from biamphiphilic triblock copolymer poly(ethylene glycol)-b-poly(ε-caprolactone)-b-poly(acrylic acid) (PEG-b-PCL-b-PAA) as new multifunctional nanocarriers to delivery anticancer drugs were evaluated. The well-defined triblock copolymers prepared by controlled polymerizations self-assembled into micelles in aqueous solution with a hydrodynamic radius of 13 nm as obtained by dynamic light scattering (DLS) and a low critical micellization concentration of 2.9 × 10(-4) g/L. The hydrophobic PCL cores of micelles were applied to load hydrophobic drug doxorubicin and the functional PAA subcoronas clung to the micellar core were used to carry cisplatin through covalent interaction. The results indicated that two anticancer drugs had been loaded by different mechanism either separately or simultaneously. Drug loading content and efficiency as well as release profiles were evaluated. Furthermore, internalization and cytotoxicity of the anticancer nanoparticles against human bladder carcinoma EJ cells were studied. The biamphiphilic triblock copolymer micelles provided not only biocompatibility and biodegradability, but also abilities for loading single and dual anticancer drugs, indicating that this was a useful multifunctional platform for anticancer drug delivery.

Synthesis of optically active 1,1′-binaphthyl-phthalocyanines linked via a crown ether unit

Abstract Novel optically active metal and metal-free phthalocyanines, substituted with 1,1′-binaphthyl crown ether units, have been synthesized and characterized.

Chiral dendrimers with axial chirality

The synthesis and optical activity of novel chiral dendrimers with axial chirality are reported. The dendrimers were constructed by coupling of the polyether dendritic bromides with (R)-(+)-1,1′-bi-2-naphthol (1). The uniform (2, 3, 4) and non-uniform double-O-alkylated (8, 9, 10) as well as mono-O-alkylated (5, 6, 7) products were thus obtained. These chiral molecules were characterized by 1H- and 13C-NMR, elemental analysis, optical rotation, adsorption spectra, and circular dichroism. It was found that the specific rotation decreases with the increase of the number of generation for each group of dendrimers (2–4, 5–7, and 8–10, respectively). In terms of the molar rotation, it was quite different; the molar rotation increased sharply for dendrimers, 2–4, but only slightly for dendrimers 5–7. The dihedral angle change of bi-naphthyl in the synthesized dendrimers was discussed based on the CD spectra. Chirality 10:661–666, 1998.

Dendrigraft polystyrene initiated by poly(p‐chloromethyl styrene): synthesis and properties

Dendrigraft polystyrene was prepared using poly(p-chloromethyl styrene) as the multicentre initiator by atom transfer radical polymerization (ATRP). The resulting polymer was characterized with light scattering, intrinsic viscosity, thermal analysis and atomic force microscopy (AFM) imaging. The AFM image showed there were two kinds of different structural dendrigraft polystyrenes in the product, ie the ‘coupling’ dendrigraft polystyrene and ‘free’ dendrigraft polystyrene. The ‘coupling’ structure might result from the coupling reaction of growing radical chain ends. The second virial coefficient A2 and intrinsic viscosity of the dendrigraft polystyrene were smaller than those of the relative linear and twelve-arm star polystyrene, and the thermal analysis showed that the initial decomposition temperature was a little higher than that of linear polystyrene. © 1999 Society of Chemical Industry

Optically active cyclic poly(ether sulfone)s based on chiral 1,1′-bi-2-naphthol

Abstract Optically active cyclic poly(ether sulfone)s are prepared from 4-fluorophenyl sulfone and ( R )- or ( S )-1,1′-bi-2-naphthol. The measurement of MALDI-TOF MS shows that the product is composed of a series of cyclic and linear oligomers where the repeating unit number ( n ) is from 2 to 12, from which the cyclic dimers ( n =2), and cyclic trimer ( n =3) have been separated from their homologous compounds by TLC successfully. Specific optical rotation [α] D 25 is −583.0 for ( R )-cyclic dimer, +588.0 for ( S )-cyclic dimer, +22.7 for ( R )-cyclic trimer, and −20.3 for ( S )-cyclic trimer. Their properties are also determined by other methods, such as 1 H NMR and CD etc.

Simple, clean preparation method for cross-linked α-cyclodextrin nanoparticles via inclusion complexation.

A simple, clean method was presented in this letter to prepare cross-linked α-cyclodextrin (α-CD) nanoparticles with a low dispersion. The nanoparticles were synthesized in water by cross-linking the inclusion complex of α-CDs and poly(ethylene glycol) (PEG). The structure of the nanoparticles was characterized by (1)H NMR, nuclear overhauser enhancement spectroscopy (NOESY), and wide-angle X-ray diffraction (XRD). Spherical morphology was observed by scanning electron microscopy (SEM) for these nanoparticles. Their average hydrodynamic radius was determined to be 67 nm by dynamic light scattering (DLS). Small guest molecules could be included in the cross-linked α-CD nanoparticles, and anticancer drug cisplatin was used to evaluate the drug release behavior.

Optically active cyclic and linear poly(aryl esters) based on chiral 1,1′-bi-2-naphthol

Abstract Three optically active poly(aryl esters)—poly(terephthalyl esters) (PTEs), poly(isophthalyl esters) (PIEs) and o -phthaloyl ester (OPE)—were prepared from chiral 1,1-bi-2-naphthol reacted with terephthaloyl chloride (TPC), isophthaloyl chloride (IPC) and o -phthaloyl chloride (OPC), respectively, by condensation reactions. The ring-forming properties of 1,1′-bi-2-naphthol with the three biacid chlorides have been studied. It is found that the products formed by the optically active binaphthol and TPC are mainly linear poly(terephthalyl esters) (PTEs), while the polycondensates of the chiral binaphthol and IPC consist of both cyclic and linear PIEs, and the product formed by optically active binaphthol and OPC is a wholly monocyclic o -phthaloyl ester (OPE), i.e. 1,1-bi-2-naphthyl o -phthalate. The pure optically active cyclic dimer, trimer and tetramer of PIEs were successfully separated from their product mixture by preparative TLC. The specific rotations [α] D 25 were +210 and −214.8 for the cyclic ( R )- and ( S )-dimer of PIEs, +177.2 and −179.1 for the cyclic ( R )- and ( S )-trimer of PIEs and +80.3 and −80.8 for the ( R )- and ( S )-tetramer of PIEs, respectively. Their characterizations were carried out by MALDI-TOF MS, GPC, CD, etc.