Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advances in tissue engineering require biofunctional scaffolds that can provide not only physical support for cells but also chemical and biological cues needed in forming functional tissues. To achieve this goal, a novel RGD peptide grafted poly(ethylene glycol)-b-poly(L-lactide)-b-poly(L-glutamic acid) (PEG-PLA-PGL/RGD) was synthesized in four steps (1) to prepare diblock copolymer PEG-PLA-OH and to convert its -OH end group into -NH(2) (to obtain PEG-PLA-NH(2)), (2) to prepare triblock copolymer PEG-PLA-PBGL by ring-opening polymerization of NCA (N-carboxyanhydride) derived from benzyl glutamate with diblock copolymer PEG-PLA-NH(2) as macroinitiator, (3) to remove the protective benzyl groups by catalytic hydrogenation of PEG-PLA-PBGL to obtain PEG-PLA-PGL, and (4) to react RGD (arginine-glycine-(aspartic amide)) with the carboxyl groups of the PEG-PLA-PGL. The structures of PEG-PLA-PGL/RGD and its precursors were confirmed by (1)H NMR, FT-IR, amino acid analysis, and XPS analysis. Addition of 5 wt % PEG-PLA-PGL/RGD into a PLGA matrix significantly improved the surface wettability of the blend films and the adhesion and proliferation behavior of human chondrocytes and 3T3 cells on the blend films. Therefore, the novel RGD-grafted triblock copolymer is expected to find application in cell or tissue engineering.
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PMID:Synthesis and characterization of RGD peptide grafted poly(ethylene glycol)-b-poly(L-lactide)-b-poly(L-glutamic acid) triblock copolymer. 1647 35

Paclitaxel is one of the most effective antineoplastic drugs. Its current clinical administration is formulated in Cremophor EL, which causes serious side effects. Nanoparticle (NP) technology may provide a solution for such poisonous adjuvant problems and promote a sustained chemotherapy, in which biodegradable polymers play a key role. Our group has successfully synthesized novel poly(lactide)-tocopheryl polyethylene glycol succinate (TPGS) (PLA-TPGS) copolymers of desired hydrophobic-hydrophilic balance for NP formulation of anticancer drugs. The present work is focused on effects of the PLA:TPGS composition ratio on drug encapsulation efficiency, in vitro drug release, in vitro cellular uptake and viability of the PLA-TPGS NP formulation of paclitaxel. The PLA-TPGS copolymers of various PLA:TPGS ratios were synthesized by the ring-opening polymerization method and characterized by GPC and (1)H NMR for their molecular structure. Paclitaxel-loaded PLA-TPGS NPs were prepared by a modified solvent extraction/evaporation method and characterized by laser light scattering for size and size distribution, scanning electron microscopy for surface morphology and zeta potential for surface charge. High performance liquid chromatography was used to measure the drug encapsulation efficiency and in vitro drug release profile. Cancer cell lines HT-29 and Caco-2 were used to image and measure the cellular uptake of fluorescent PLA-TPGS NPs. Cancer cell viability of the drug-loaded PLA-TPGS was measured by MTT assay. It was found that the PLA:TPGS composition ratio has little effects on the particle size and size distribution. However, the PLA-TPGS NPs of 89:11 PLA:TPGS ratio achieved the best effects on the drug encapsulation efficiency, the cellular uptake and the cancer cell mortality of the drug-loaded PLA-TPGS NPs. This research was also carried out in close comparison with the drug-loaded PLGA NPs.
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PMID:The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly(lactide)-tocopheryl polyethylene glycol succinate nanoparticles. 1656 85

Polysorbate 80 (Tween 80) has been widely used as an emulsifier with excellent effects in nanoparticles technology for biomedical applications. This work was thus triggered to synthesize poly(lactide)/Tween 80 copolymers with various copolymer blend ratio, which were synthesized by ring-opening polymerization and characterized by 1H NMR and TGA. Nanoparticles of poly(lactide)/Tween 80 copolymers were prepared by the dialysis method without surfactants/emulsifiers involved. Paclitaxel was chosen as a prototype anticancer drug due to its excellent therapeutic effects against a wide spectrum of cancers. The drug-loaded nanoparticles of poly(lactide)/Tween 80 copolymers were then characterized by various state-of-the-art techniques, including laser light scattering for particles size and size distribution, field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) for surface morphology; laser Doppler anemometry for zeta potential; differential scanning calorimetry (DSC) for the physical status of the drug encapsulated in the polymeric matrix; X-ray photoelectron spectrometer (XPS) for surface chemistry; high performance liquid chromatography (HPLC) for drug encapsulation efficiency; and in vitro drug release kinetics. HT-29 cells and Glioma C6 cells were used as an in vitro model of the GI barrier for oral chemotherapy and a brain cancer model to evaluate in vitro cytotoxicity of the paclitaxel-loaded nanoparticles. The viability of C6 cells was decreased from 37.4 +/- 4.0% for poly(D,L-lactide-co-glycolic acid) (PLGA) nanoparticles to 17.8 +/- 4.2% for PLA-Tween 80-10 and 12.0 +/- 5.4% for PLA-Tween 80-20 copolymer nanoparticles, which was comparable with that for Taxol at the same 50 microg/mL drug concentration.
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PMID:In vitro investigation on poly(lactide)-Tween 80 copolymer nanoparticles fabricated by dialysis method for chemotherapy. 1660 31

Some biodegradable amphiphilic copolymers were synthesized by conjugating poly(DL-lactic acid) (PLA) onto ethylenediamino or diethylenetriamino bridged bis(beta-cyclodextrin)s (bis-CDs). Double emulsion (DE) and nanoprecipitation (NP) methods were used to fabricate the nanoparticles of these copolymers entrapping bovine serum albumin (BSA) as a model protein. Effects of the experimental parameters, such as copolymer composition, BSA concentration, copolymer concentration and poly(vinyl alcohol) concentration, on particular size and encapsulation efficiency (EE) were investigated. Their EE to BSA could reach 83.5% at an optimized condition owing to the cooperative binding effect of the CD moiety with BSA. The core-corona structure of copolymer micelles fabricated from the nanoprecipitation was studied on the basis of 1H NMR and other measurements at various temperatures. The results showed that the core-corona structure kept stable below 50 degrees C (lower than Tg). And increase of the micelle association number occurred above the Tg because the size of the NPs became larger and proton signals of the liquid-like PLA cores could be observed in 1H NMR in D2O at 60 degrees C. The release profiles of NPs showed a burst effect followed by a continuous release. Sodium dodecyl sulfate polyacrylamide gel electrophoresis, circular dichroic and fluorescence spectra were further used to identify the stability of BSA released from the NPs. The nanoparticles from the conjugates have a promising potential in nasal delivery system.
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PMID:Conjugates of poly(DL-lactic acid) with ethylenediamino or diethylenetriamino bridged bis(beta-cyclodextrin)s and their nanoparticles as protein delivery systems. 1661 67

Novel amphiphilic methoxy-poly(ethylene glycol)-poly(hexyl-substituted lactides) block copolymers were synthesized by ring-opening polymerization (ROP) of mono and dihexyl-substituted lactide (mHLA and diHLA) in bulk at 100 degrees C in the presence of tin(II) 2-ethylhexanoate (Sn(Oct)(2)) as catalyst and methoxy-poly(ethylene glycol) (MPEG) as initiator. MPEG-PmHLA and MPEG-PdiHLA copolymers of predictable molecular weights and narrow polydispersities were obtained, as shown by (1)H NMR and GPC. DSC experiments showed that the MPEG-PHLA block-copolymer presents a bulk microstructure containing MPEG domains segregated from the PHLA domains. Micelles were successfully prepared from these block copolymers, with sizes ranging from 30 to 80 nm. The critical micellar concentration (CMC) was found to decrease with the increasing number of hexyl groups on the polyester block (MPEG-PLA > MPEG-PmHLA > MPEG-PdiHLA) for copolymers of the same composition and molecular weight. The hydrophobicity of the micelle core in dependence of the number of hexyl groups along the PLA chain was evidenced by absorbance experiments with the incorporation of the dye Nile Red. These novel amphiphilic copolymers are interesting for micellar drug delivery and especially in regard to optimized hydrophobic drug loadings, as it was shown for griseofulvin as a model drug.
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PMID:Novel polymeric micelles for hydrophobic drug delivery based on biodegradable poly(hexyl-substituted lactides). 1671 91

The functions of the serpin PAI-1 (plasminogen activator inhibitor-1) are based on molecular interactions with its target proteases uPA and tPA (urokinase-type and tissue-type plasminogen activator respectively), with vitronectin and with endocytosis receptors of the low-density-lipoprotein family. Understanding the significance of these interactions would be facilitated by the ability to block them individually. Using phage display, we have identified the disulfide-constrained peptide motif CFGWC with affinity for natural human PAI-1. The three-dimensional structure of a peptide containing this motif (DVPCFGWCQDA) was determined by liquid-state NMR spectroscopy. A binding site in the so-called flexible joint region of PAI-1 was suggested by molecular modelling and validated through binding studies with various competitors and site-directed mutagenesis of PAI-1. The peptide with an N-terminal biotin inhibited the binding of the uPA-PAI-1 complex to the endocytosis receptors low-density-lipoprotein-receptor-related protein 1A (LRP-1A) and very-low-density-lipoprotein receptor (VLDLR) in vitro and inhibited endocytosis of the uPA-PAI-1 complex in U937 cells. We conclude that the isolated peptide represents a novel approach to pharmacological interference with the functions of PAI-1 based on inhibition of one specific molecular interaction.
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PMID:Inhibition of plasminogen activator inhibitor-1 binding to endocytosis receptors of the low-density-lipoprotein receptor family by a peptide isolated from a phage display library. 1681 66

Ring-opening polymerization of D,L-lactide was carried out in the presence of monohydroxylated poly(ethylene glycol) (PEG) with Mn of 2000 and 5000, using zinc powder as catalyst. The resulting PEG-b-polylactide (PEG-PLA) diblocks with various ethylene oxide/lactyl (EO/LA) ratios were coupled with adipoyl chloride to yield PEG-PLA-PEG triblock copolymers. N-Dimethylaminopyridine (DMAP) was used as catalyst. The obtained PEG-PLA-PEG triblock copolymers were characterized by various analytical techniques such as IR, 1H NMR, size exclusion chromatography, X-ray diffraction, and differential scanning calorimetry. Data showed that all the copolymers were semicrystalline with the PEG-type crystalline structure, the crystallinity decreasing with increasing PLA block length. Bioresorbable hydrogels were prepared from the water-soluble triblock copolymers. Rheological measurements showed a gel-sol transition with increasing temperature and gelation was found to be thermoreversible. The copolymer solution behaves like a viscoelastic liquid above the gel point and like a viscoelastic solid below the gel point. The critical gelation concentration, the gel-sol transition temperature at a given concentration, and corresponding moduli depend on both the EO/LA ratio and the molecular weight of the copolymers. It is assumed that gelation results from interactions between PEG blocks at low temperatures and that these interactions are disrupted as the temperature is elevated. The shrinking of PEG blocks with increasing temperature seems to be in agreement with the variation of the gel-sol transition temperatures.
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PMID:Synthesis and gelation properties of PEG-PLA-PEG triblock copolymers obtained by coupling monohydroxylated PEG-PLA with adipoyl chloride. 1724 42

We reported previously that the methanolic root extract of the Indian medicinal plant Pluchea indica Less. (Asteraceae) could neutralize viper venom-induced action [Alam, M.I., Auddy, B., Gomes, A., 1996. Viper venom neutralization by Indian medicinal plant (Hemidesmus indicus and P. indica) root extracts. Phytother. Res. 10, 58-61]. The present study reports the neutralization of viper and cobra venom by beta-sitosterol and stigmasterol isolated from the root extract of P. indica Less. (Asteraceae). The active fraction (containing the major compound beta-sitosterol and the minor compound stigmasterol) was isolated and purified by silica gel column chromatography and the structure was determined using spectroscopic analysis (EIMS, (1)H NMR, (13)C NMR). Anti-snake venom activity was studied in experimental animals. The active fraction was found to significantly neutralize viper venom-induced lethal, hemorrhagic, defibrinogenation, edema and PLA(2) activity. Cobra venom-induced lethality, cardiotoxicity, neurotoxicity, respiratory changes and PLA(2) activity were also antagonized by the active component. It potentiated commercial snake venom antiserum action against venom-induced lethality in male albino mice. The active fraction could antagonize venom-induced changes in lipid peroxidation and superoxide dismutase activity. This study suggests that beta-sitosterol and stigmasterol may play an important role, along with antiserum, in neutralizing snake venom-induced actions.
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PMID:Viper and cobra venom neutralization by beta-sitosterol and stigmasterol isolated from the root extract of Pluchea indica Less. (Asteraceae). 1729 96

To design novel bioinspired polymeric material, poly(D,L-lactic acid) (DL-PLA) was on the base and modified in the bulk. Firstly, maleic anhydride (MA) groups were introduced to the side chain of DL-PLA by the way of melting free radical copolymerization using benzoyl peroxide as an initiator. Then, to neutralize the acid generated during DL-PLA degradation, aliphatic diamine was immobilized by the N-acylation of anhydrides with butanediamine. As the following stage, adhesive peptides Arg-Gly-Asp-Ser (RGDS) were grafted into the backbone of DL-PLA by using carbodiimide as a coupling agent, in order to endow DL-PLA with bioactivity and biospecificity. The characterizations of the obtained polymers were by the means of GPC-MALLS, FTIR, (13)C NMR and XPS to explore the structures and rhodamine-carboxyl interaction method, ninhydrin reaction and amino acid analyzer to determine the content of MA, butanediamine, and RGDS, respectively, followed the test of pH changes during degradation in distilled water (pH = 6.45). Finally, the osteoblast behavior on different DL-PLA based films was investigated and the results indicated that the introduction of diamine could promote cell attachment and viability, and the incorporation of RGDS further improved its cytocompatibility. The synthetic DL-PLA based bioinspired material may have potentials for tissue engineering and other biomedical applications.
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PMID:Design of bioinspired polymeric materials based on poly(D,L-lactic acid) modifications towards improving its cytocompatibility. 1764 23

A biodegradable Copolymer of poly(lactic acid-co-lysine)(PLA-PLL) was synthesized by a modified method and novel Arginine-Glycine-Aspartic (RGD) peptides were chemical conjugated to the primary epsilon-amine groups of lysine components in four steps: I to prepare the monomer of 3-(Nepsilon-benzoxycarbonyl-L-lysine)-6-L-methyl-2,5-morpholinedione; II to prepare diblock copolymer poly(lactic acid-co-(Z)-L-lysine) (PLA-PLL(Z)) by ring-opening polymerization of monomer and L,L-lactide with stannous octoate as initiator; III to prepare diblock copolymer PLA-PLL by deprotected the copolymer PLA-PLL(Z) in HBr/HoAc solution; IV the reaction between RGD and the primary epsilon-amine groups of the PLA-PLL. The structure of PLA-PLL-RGD and its precursors were conformed by FTIR-Raman and 1H NMR. Low weight average molecular weight (9,200 g/mol) of the PLA-PLL was obtained and its PDI is 1.33 determined by GPC. The PLA-PLL contained 2.1 mol% lysine groups as determined by 1H NMR using the lysine protecting group's phenyl protons. Therefore, the novel RGD-grafted diblock copolymer is expected to find application in drug carriers for tumor therapy or non-viral DNA carriers for gene therapy.
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PMID:Synthesis and characterization of arginine-glycine-aspartic peptides conjugated poly(lactic acid-co-L-lysine) diblock copolymer. 1770 54


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