Structural optimization of HPMA copolymer-based dexamethasone prodrug for improved treatment of inflammatory arthritis
摘要:
Despite their notorious adverse effects, glucocorticoids (GC, potent anti-inflammatory drugs) are used extensively in clinical management of rheumatoid arthritis (RA) and other chronic inflammatory diseases. To achieve a sustained therapeutic efficacy and reduced toxicities, macromolecular GC prodrugs have been developed with promising outcomes for the treatment of RA. Fine-tuning the activation kinetics of these prodrugs may further improve their therapeutic efficacy and minimize the off-target adverse effects. To assess the feasibility of this strategy, five different dexamethasone (Dex, a potent GC)-containing monomers with distinctively different linker chemistries were designed, synthesized, and copolymerized with N-(2-hydroxypropyl) methacrylamide (HPMA) to obtain 5 macromolecular Dex prodrugs. Their Dex releasing rates were analyzed in vitro and shown to display a wide spectrum of activation kinetics. Their therapeutic efficacy and preliminary toxicology profiles were assessed and compared in vivo in an adjuvant-induced arthritis (AA) rat model in order to identify the ideal prodrug design for the most effective and safe treatment of inflammatory arthritis. The in vivo data demonstrated that the C3 hydrazone linker-containing prodrug design was the most effective in preserving joint structural integrity. The results from this study suggest that the design and screening of different activation mechanisms may help to identify macromolecular prodrugs with the most potent therapeutic efficacy and safety for the management of inflammatory arthritis.
PRODUCTION OF OPHTHALMIC DEVICES BASED ON PHOTO-INDUCED STEP GROWTH POLYMERIZATION
申请人:Medina Arturo Norberto
公开号:US20110269869A1
公开(公告)日:2011-11-03
The invention provide a new lens curing method for making hydrogel contact lenses. The new lens curing method is based on actinically-induced step-growth polymerization. The invention also provides hydrogel contact lenses prepared from the method of the invention and fluid compositions for making hydrogel contact lenses based on the new lens curing method. In addition, the invention provide prepolymers capable of undergoing actinically-induced step-growth polymerization to form hydrogel contact lenses.
[EN] FORCE-RESPONSIVE POLYMERSOMES AND NANOREACTORS; PROCESSES UTILIZING THE SAME<br/>[FR] POLYMERSOMES ET NANORÉACTEURS SENSIBLES À LA FORCE; PROCÉDÉS LES UTILISANT
申请人:ADOLPHE MERKLE INSTITUTE UNIV OF FRIBOURG
公开号:WO2019034597A1
公开(公告)日:2019-02-21
The mechanically induced melting properties of DNA were employed to achieve force labile membranes is described. Nucleobase pairs were used as mechanophores. Adenine and thymine functionalized complementary amphiphilic block copolymers were self-assembled into polymersomes. The nucleobases formed hydrogen bonds which were disrupted upon force stimulation. The exposure of the disconnected nucleobases to the hydrophobic matrix of the membranes lead to a change of permeability which permitted the exchange of water-soluble molecules throughout the polymer matrix. Moreover, the encapsulation of horseradish peroxidase enabled the reaction of luminol with hydrogen peroxide to yield a luminescence producing species similar to the marine bioluminescence. Moreover, the same nano-reactors were employed to catalyze the formation of a polyacrylamide gel when force was applied. Insights into the change of permeability of supramolecular networks upon force are provided. These systems are useful for drug delivery, as nanoreactors and for the selective release of curing agents for 3D printing, or fragrances.
Process for preparing vinyl substituted beta-diketones
申请人:Southard E. Glen
公开号:US20060069288A1
公开(公告)日:2006-03-30
A process for preparing vinyl substituted beta-diketones includes reacting a halogen-containing beta-diketone with an olefin in a reaction zone under Heck coupling reaction conditions in the presence of a catalyst, a base, and an organic phosphine to provide a vinyl substituted beta-diketone product.
POLYMERIC SYSTEMS FOR THE DELIVERY OF ANTICANCER DRUGS
申请人:Lee Young B.
公开号:US20110086111A1
公开(公告)日:2011-04-14
The present invention relates to compositions for the treatment of cancerous tissues in warm-blooded animals containing one or two anticancer agents attached to polymeric carriers having monomer units derived from one or more of N-(2-carboxypropyl)methacrylamide (2-CPMA), N-(3-carboxypropyl)methacrylamide (3-CPMA), N-(2-aminopropyl)methacrylamide (2-APMA) and/or N-(3-aminopropyl)methacrylamide (3-APMA) are also included. Anticancer agents in compositions can be attached to said polymeric carrier by side-chains which can be susceptible to hydrolysis by lysosomal enzymes intracellularly. Compositions can also include a targeting ligand attached to the polymeric carrier, optionally through a second linker.
The present invention relates to a method for purifying nucleic acids using a nucleic acid-binding phase which is furnished with a deficit of nucleic acid-binding groups A having a pK of 8 to 13, or which has groups A and binding-inhibiting groups N which are neutrally charged during the binding, and preferably during the elution, and the method comprises the following steps: (a) binding the nucleic acids to the nucleic acid-binding phase at a pH which is below the pH of the pK of the nucleic acid-binding groups A (binding pH); (b) eluting the nucleic acids at a pH which is above the binding pH (elution pH). In addition, corresponding kits and also nucleic acid-binding phases which can be used for purifying nucleic acids are disclosed. The technology according to the invention permits the purification of nucleic acids and, in particular, elution, with use of low salt concentrations, and so the purified nucleic acids can be directly processed, for example used in a PCR.