Preparation and physicochemical properties of konjac glucomannan ibuprofen ester as a polysaccharide-drug conjugate

Abstract

A novel drug-polysaccharide conjugate with konjac glucomannan (KGM) as a drug carrier was fabricated through the esterification of ibuprofen (IBU), an anti-inflammatory drug, with KGM. The influences of the reaction conditions, such as the amount of ibuprofen acryl chloride, reaction time, reaction temperature, and the amount of catalyst, on the degree of substitution were investigated. KGM ibuprofen ester (KGM-IBU) was characterized by Fourier transform infrared spectrometry (FTIR), X-ray diffraction (XRD), solid-state ¹³C NMR, scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic mechanical analysis (DMA). The hydrophobic structure of IBU in KGM-IBU was proven by the fluorescence emission spectra of pyrene. In addition, by using commercially available ibuprofen sustained-release capsules (IBU-SRC) as a control, the in vitro controlled release performance of KGM-IBU was evaluated. The cumulative release of IBU-SRC within 36?h was 94%, while that of KGM-IBU within 36?h was 77%. The results showed that KGM-IBU had better sustained-release performance without a burst release effect. The obtained products could be used as a potential biocompatible sustained-release drug delivery system.     

Preparation of a multitopic glycopeptide-oligonucleotide conjugate

[structure: see text] A novel strategy to prepare glycopeptide-oligonucleotide conjugates bearing a glycocluster is reported. The strategy utilizes a cyclodecapeptide scaffold as a key intermediate to anchor the carbohydrate cluster and the oligonucleotide through sequential oxime bond formation. The oligonucleotide glycocluster retains the binding affinity and recognition specificity for the target sequence. Furthermore, the conjugate shows enhanced binding to the specific lectins due to the cooperative effect produced by the carbohydrate cluster.     

Synthesis and properties of a surfactant-cyclodextrin conjugate

A surfactant-cyclodextrin conjugate. in which an ion-terminated chain is attached to each of the seven cyclodextrin sugars, has been synthesized and examined by a variety of physical methods.     

Macromolecular conjugate based particulates: Preparation, characterisation and evaluation of controlled release properties

A new particulate delivery matrix based on macromolecular conjugate, chitosan-whey protein isolate ([Ch-WPI]) was found to exhibit controlled release properties. Fourier-Transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) demonstrated the formation of the conjugate. Particle formation of the conjugate was carried out by the ionic crosslinking technique using sodium tripolyphospate (STP). Catechin entrapped particles were prepared by varying the weight ratios of STP to conjugate [Ch-WPI]. Both the placebo and catechin-entrapped particles were found to be positively charged below pH 7.2, indicating their stability to aggregation and their suitability for bioadhesion in the gastrointestinal tract (GIT). The entrapment efficiencies of the particles ranged between 29% and 42% for particles prepared using different weight ratios of the conjugate to STP. There was 34-56% of catechin release in simulated GIT conditions depending on the entrapment efficiencies and the degree of crosslinking of the particles.     

Photochemical properties of a myoglobin-CdTe quantum dot conjugate

A myoglobin-cadmium telluride quantum dot conjugate was constructed using an artificial heme modified with a thiol moiety as a linker. Irradiation of the myoglobin-cadmium telluride conjugate generated the photoreduced ferrous myoglobin via an electron transfer from the photoexcited quantum dot, leading to the formation of CO-bound myoglobin under a CO atmosphere.     

Synthesis and properties of PI polyamide-SAHA conjugate

We have designed and synthesized new types of pyrrole (P)-imidazole (I) polyamide conjugates 1 and 2 possessing a suberoylanilide hydroxamic acid (SAHA) moiety that is a strong inhibitor of histone deacetylase (HDAC). SAHA conjugate 2 was designed to target the promoter region of the p16 tumor suppressor gene. The DNA binding affinity of SAHA conjugate 2 to its target sequence was examined using surface plasmon resonance. HDAC inhibition activity of conjugates 1 and 2 was evaluated using a colorimetric assay. The results demonstrated that even though it possesses the relatively large SAHA moiety, conjugate 2 has high DNA sequence-specific binding properties and moderate HDAC inhibitory activity in vitro. SAHA conjugate 2 was found to cause morphological changes in HeLa cells and to induce selective Histone H3 lysine 9 acetylation.     

Synthesis and antitumor activities of mitomycin C (1----3)-beta-D-glucan conjugate.

The conjugate of mitomycin C (MMC) with linear (1----3)-beta-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 was synthesized and its antitumor activities investigated. The conjugate (MMC-carboxymethylated linear (1----3)-beta-D-glucan (CMPS)) was obtained by treatment of CMPS with MMC in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. In vitro cytotoxicity of MMC-CMPS against L1210 leukemia cells was similar to that of MMC. In i.p.-i.p. system in vivo against P388 leukemia in mice, the maximum increase of MMC-CMPS conjugate in life span (ILSmax) was higher than that of MMC but the therapeutic index was reduced. However, the antitumor activity of MMC-CMPS conjugate against subcutaneously implanted sarcoma 180 solid tumor in mice by i.p. administration was similar to that of MMC at a dose of 1.5 mg eq MMC/kg/d x 7 and the reduction of the number of leukocytes caused by MMC was suppressed by attaching MMC to CMPS. In addition, on assay using serum of sarcoma 180 solid tumor-bearing mice with injection of MMC-CMPS conjugate, a drastic loss of tumor cells and an increase in polymorphonuclear leukocytes (PMN) were observed. This result suggested that MMC-CMPS conjugate induced tumor-regressing factor similar to CMPS.     

Synthesis, characterization, and supramolecular properties of a hydrophilic porphyrin--beta-cyclodextrin conjugate

Reductive amination of 6-deoxy-6-formyl-beta-cyclodextrin with 5-(p-aminophenyl)-10,15,20-tris(p-sulfonatophenyl)porphyrin in the presence of an excess of sodium cyanoborohydride affords the hydrophilic cyclodextrin-porphyrin conjugate 3 in 23% yield. The structure of 3 was confirmed by NMR spectroscopy and mass spectrometry techniques. Compound 3 showed a marked tendency to dimerize in aqueous conditions via the formation of intermolecular porphyrin-cyclodextrin inclusion complexes and/or through electrostatic interactions. Information on the structure of these aggregates has been obtained by the use of circular dichroism and UV-vis spectroscopy. Aggregation can be avoided by the use of heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TM beta CD) that forms a 1:1 inclusion complex with compound 3.     

Synthesis and cholera toxin binding properties of a lactose-2-aminothiazoline conjugate

[structure: see text] During the search for improved monovalent ligands for cholera toxin (CT), a new lactose-2-aminothiazoline conjugate was discovered. In a fluorescence binding assay the compound was found to be one of the strongest relatively simple CT ligands to date with a K(d) of 23 microM.     

Preparation and properties of a thermo-sensitive latex film

Polymer particles with hydrophobic core and hydrophilic shell were prepared via a three-step method. First, poly(butyl methacrylate-co-methyl methacrylate) (p-(BMA-MMA)) latex was prepared through emulsion polymerization. Then, a shell of poly(glycidyl methacrylate) (p-GMA) was introduced around the p-(BMA-MMA) particles by using a redox initiation system under kinetically controlled conditions. Finally, part of the epoxy groups existing in the shell were converted into quaternary ammonium salts, resulting in an ionic hydrophilic shell. The core-shell particles could be redispersed in water to form a stable emulsion. The contact angle of the core-shell latex film with water was around 16° at 25 °C, which became larger than 90° after the film was heated at 150 °C for a short period of time. This showed that the latex film was completely switched from hydrophilicity to hydrophobicity by the action of heat. Additionally, the latex film before heat treatment could be easily washed away from the substrate with neutral water, but it could no longer be removed after the heat treatment. When an IR dye with the maximum absorption at 830 nm was incorporated into the film, it became sensitive to LD laser emitting at 830 nm and gave negative image after exposed by LD laser and developed with neutral water. This showed that the latex film might find uses in chemical-free thermal laser imaging applications.     

A new ferrocene conjugate of a tyrosine PNA monomer: synthesis and electrochemical properties

A new chiral ferrocene-labelled tyrosine PNA monomer 1 has been synthesised in good yield in both racemic and enantiomerically pure forms. It is suitable for insertion in various positions of PNA oligomers, a possibility that has been preliminarily demonstrated by synthesising the dimer 16. Moreover, in view of possible applications to nucleic acid detection, a preliminary voltammetric investigation on the electrochemical activity of monomer 1 and its synthetic precursors has been carried out in DMF. It appears that, despite the bulkiness of the PNA monomer backbone, its insertion on the ferrocene group only moderately lowers the latter’s diffusion coefficients and peak currents, thus affording voltammetric detection limits in the order of 10⁻⁶-10⁻⁷ M.     

A photochromic porphyrin-perinaphthothioindigo conjugate and its two-photon absorption properties

A porphyrin-perinaphthothioindigo conjugate having two-photon absorption cross-sections of approximately 2000 GM and approximately 700 GM for trans- and cis-isomers, respectively, was synthesized and exhibited clear photochromic behavior upon one-photon and two-photon excitation.     

The chemical synthesis and antiviral properties of an acyclovir-phospholipid conjugate

The synthesis of acyclovir-phospholipid conjugate (2) is reported through an unambiguous one-step preparation of L-alpha-dimyristoyl phosphatidic acid triethylammonium salt (5). The biological activity of 2 as an antiviral drug has also been investigated.     

Preparation and properties of borosilicates with a zeolite structure

The dependence of the state of boron atoms on the preparation conditions of borosilicates and the effect of this state on their catalytic properties in methanol conversion have been studied.

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