Ren Xi Zhuo

In vitro release of 5-fluorouracil with cyclic core dendritic polymer

This paper describes the first synthesis of a series of dendritic polymers with a core of 1,4,7,10-tetraazacyclododecane. This core was allowed to react with methyl acrylate through a Michael addition and was then amidated with ethylenediamine. Repeating the two steps led to controlled molecular weight increasing and branching on the molecular level and produced four direction poly(amide-amine) dendrimers. We successfully synthesized dendrimers from generation 0. 5 to generation 5.5. Each generation was analyzed by Fourier- transform infrared (FT-IR) spectroscopy, 1H NMR and elemental analysis. Titrimetry was also used to determine the number of -NH2 of each full generation (2.0, 3.0, 4.0, 5.0). SEC (size exclusion chromatography) was performed to test the purity of G-3.0, G-4.0 and G-5.0. Parts of the outer layer -NH2 groups of the dendrimers generation 4 and generation 5 were acylated by acetic anhydride. The solubility in water of the dendrimer was thus greatly enhanced. The acetylated dendrimers were then reacted with 1-bromoacetyl-5-fluorouracil to form dendrimer-5FU conjugates. Hydrolysis of the conjugates in a phosphate buffer solution (pH 7.4) at 37 degreesC will release free 5FU. Different generation of dendrimer-5FU conjugates exert marking influence on the amount of 5FU released. The dendritic polymer seems to be a promising carrier for the controlled release of antitumor drugs.

Graphene-based anticancer nanosystem and its biosafety evaluation using a zebrafish model.

In this paper, a facile strategy to develop graphene-based delivery nanosystems for effective drug loading and sustained drug release was proposed and validated. Specifically, biocompatible naphthalene-terminated PEG (NP) and anticancer drugs (curcumin or doxorubicin (DOX)) were simultaneously integrated onto oxidized graphene (GO), leading to self-assembled, nanosized complexes. It was found that the oxidation degree of GO had a significant impact on the drug-loading efficiency and the structural stability of nanosystems. Interestingly, the nanoassemblies resulted in more effective cellular entry of DOX in comparison with free DOX or DOX-loaded PEG-polyester micelles at equivalent DOX dose, as demonstrated by confocal microscopy studies. Moreover, the nanoassemblies not only exhibited a sustained drug release pattern without an initial burst release, but also significantly improved the stability of formulations which were resistant to drug leaking even in the presence of strong surfactants such as aromatic sodium benzenesulfonate (SBen) and aliphatic sodium dodecylsulfonate (SDS). In addition, the nanoassemblies without DOX loading showed negligible in vitro cytotoxicity, whereas DOX-loaded counterparts led to considerable toxicity against HeLa cells. The DOX-mediated cytotoxicity of the graphene-based formulation was around 20 folds lower than that of free DOX, most likely due to the slow DOX release from complexes. A zebrafish model was established to assess the in vivo safety profile of curcumin-loaded nanosystems. The results showed they were able to excrete from the zebrafish body rapidly and had nearly no influence on the zebrafish upgrowth. Those encouraging results may prompt the advance of graphene-based nanotherapeutics for biomedical applications.

Self-assembled, thermoresponsive micelles based on triblock PMMA-b-PNIPAAm-b-PMMA copolymer for drug delivery

A novel thermosensitive amphiphilic ABA triblock poly(methyl methacrylate)-b-poly(N-isopropylacrylamide)-b-poly(methyl methacrylate) copolymer (PMMA-b-PNIPAAm-b-PMMA) comprised of two hydrophobic PMMA segments and one hydrophilic PNIPAAm segment was designed and synthesized. The structure of the copolymer was characterized by FT-IR, 1HNMR, and GPC analysis. The cytotoxicity study showed that the PMMA-b-PNIPAAm-b-PMMA copolymer exhibited low cytotoxicity. The copolymer was capable of self-assembling into micelles in water and demonstrated temperature sensitivity at around 34.5u2009°C. Transmission electron microscopy (TEM) showed that the micelles exhibit nanosized spherical morphology within a size range of 60xa0nm with a critical micellar concentration (CMC) at 10xa0mgxa0l−1. The drug-loading PMMA-b-PNIPAAm-b-PMMA micelles showed thermosensitive-controlled release which indicates the potential of PMMA-b-PNIPAAm-b-PMMA micelles as drug carriers.

A boronate-linked linear-hyperbranched polymeric nanovehicle for pH-dependent tumor-targeted drug delivery.

Advanced drug delivery systems, which possess post-functionalization feasibility to achieve targetability and traceability, favorable pharmacokinetics with dynamic but controllable stability, and preferable tumor accumulation with prolonged drug residence in disease sites, represent ideal nanomedicine paradigm for tumor therapy. To address this challenge, here we reported a dynamic module-assembly strategy based on reversible boronic acid/1,3-diol bioorthogonality. As a prototype, metastable hybrid nanoself-assembly between hydrophobic hyperbranched diol-enriched polycarbonate (HP-OH) and hydrophilic linear PEG terminated with phenylboronic acid (mPEG-PBA) is demonstrated in vitro and in vivo. The nanoconstruction maintained excellent stability with little leakage of loaded drugs under the simulated physiological conditions. Such a stable nanostructure enabled the effective in vivo tumor accumulation in tumor site as revealed by NIR imaging technique. More importantly, this nanoconstruction presented a pH-labile destruction profile in response to acidic microenvironment and simultaneously the fast liberation of loaded drugs. Accordingly at the cellular level, the intracellular structural dissociation was also proved in terms of the strong acidity in late endosome/lysosome, thus favoring the prolonged retention of remaining drug-loaded HP-OH aggregates within tumor cells. Hence, our delicate design open up a dynamical module-assembly path to develop site and time dual-controlled nanotherapeutics for tumor chemotherapy, allowing enhanced tumor selectivity through prolonged retention of delivery system in tumor cells followed by a timely drug release pattern.

Synthesis, Characterization and In Vitro Cytotoxicity of Poly[(5‐benzyloxy‐trimethylene carbonate)‐co‐(trimethylene carbonate)]

The ring-opening copolymerization of 5-benzyloxy-trimethylene carbonate (BTMC) with trimethylene carbonate (TMC) was described. The polymerization was carried out in bulk at 150 °C using stannous octanoate as initiator. The influence of reaction conditions such as polymerization time and initiator concentration on the yield and molecular weight of the copolymers were investigated. The poly(BTMC-co-TMC)s obtained were characterized by FT-IR, 1 H NMR, 13 C NMR, GPC and DSC. NMR results of copolymer showed no evidence for decarboxylation occurring during the propagation. The relation- ship between the copolymer glass transition temperature and composition was in agreement with the Fox equation. The in vitro cytotoxicity studies of the poly(BTMC-co- TMC) (50:50) using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay demonstrated that the copolymer has low cytotoxicity compared to poly[(lactic acid)-co-(glycolic acid)] (75:25).

Bioactive materials in gene therapy

Abstract: Gene therapy is a new form of molecular medicine to cure the inherited or acquired diseases through delivering therapeutic genes to targeted cells and replacing the disorder genes. Nowadays, large numbers of non-viral gene vectors, including cationic liposomes and polycations, have attracted much attention due to their lower immune response, simpler preparation and greater stability as compared with viral vectors. Based on the concise introduction of cell biology, this chapter reviews the most significant non-viral gene delivery systems, and introduces current strategies for non-viral gene delivery in vitro and in vivo .

PREPARATIONS AND PROPERTIES OF SOME PHOSPHORUS- CONTAINING DIALDEHYDES AND DIALCOHOLS

Abstract Di(4-formyl-2-methoxyphenyl)phosphates (DFMPP) were synthesized by the condensation of vanillin with phosphoryldichlorides. The di(4-hydroxymethyl-2-ethoxyphenyl)phosphates (DHMPP) were prepared by the reduction of DFMPP with potassium borohydride. The 31P-1H coupling in DFMPP (compounds 1a-h) was investigated and the splitting of the 31P signal by the 1H nuclei was observed only with the alkyl DFMPP (1a-e). In the non-decoupled 31P spectra a quartet at −11.3 ppm was seen for la (P-OCH 3) with JPH=11.4 Hz, and a triplet for 1b, 1c, 1d and 1e respectively (1b, P-OCH 2 δ= - 12.3 ppm, JPH=8.4 Hz; 1c, P-OCH 2CH2CH3, δ= - 12.6 ppm, JPH=7.1 Hz; 1d, P-OCH 2CH2CH2CH3, δ= - 12.9 ppm, JPH=8.4 Hz and le, P-OCH 2CH2Cl, δ= - 13.0 ppm, JPH = 8.1 Hz).