- Synthesis and chemical degradation of branched vinyl polymers prepared via ATRP: Use of a cleavable disulfide-based branching agent
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Highly branched poly(2-hydroxypropyl methacrylate) has been prepared by atom transfer radical polymerization (ATRP) in methanol at 20°C using a disulfide-based dimethacrylate (DSDMA) branching agent. The mean degree of polymerization of the primary chains was fixed at 50; since ATRP has reasonably good living character, the molecular weight distribution of these primary chains is relatively narrow, which allows significantly better control than conventional radical polymerization. Varying the proportion of the DSDMA produced a series of soluble branched polymers, provided that there was on average less than one branching agent per primary chain. However, higher levels of DSDMA lead to macrogelation, as expected. The soluble branched polymers were characterized using triple detector gel permeation chromatography (GPC). The most highly branched copolymers had weight-average molecular weights of up to 540 000, with polydispersities of around 8.0 and Mark-Houwink a parameters as low as 0.21 being obtained. 1H NMR spectroscopy confirmed that very high monomer conversions were obtained (>99%), and the final branched copolymers contained little or no unreacted pendent vinyl groups. The disulfide bond in the DSDMA branching agent was readily cleaved using either dithiothreitol or benzoyl peroxide. GPC studies confirmed the progressive decrease in molecular weight and polydispersity during the chemical degradation of one of the branched copolymers with reaction time. Eventually, the final polydispersity of this degraded branched copolymer was comparable to that of linear poly(2-hydroxypropyl methacrylate) prepared in the absence of any disulfide-based dimethacrylate branching agent. Thus, all the disulfide bonds had been cleaved, reducing the branched copolymer to its near-monodisperse primary chains.
- Li, Yuting,Armes, Steven P.
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- Synthesis of degradable miktoarm star copolymers via atom transfer radical polymerization
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Both nondegradable and degradable miktoarm star copolymers were synthesized via ATRP using the "in-out" method. The synthesis consisted of three steps: synthesis of a linear macroinitiator (MI) using the first monomer, a core-forming reaction with a divinyl compound, and then further chain extension with the second monomer. Various characterization methods, including GPC, NMR, and GC, were used to analyze the initial star polymers and to identify the optimal experimental conditions for the synthesis of the multifunctional star initiators and the miktoarm star copolymers. During the synthesis of miktoarm star copolymers, both interstar and intrastar arm-arm couplings were observed. The initiating efficiency of the alkyl bromide sites in the core of the star polymers was determined by analysis of the linear block copolymers, obtained after cleavage of the degradable star and miktoarm star copolymers. The results confirmed that the initiation efficiency was reduced by the highly cross-linked star core. In the case of degradable miktoarm star copolymers, only 19% of the total Br functionality incorporated into the first star copolymer initiated the polymerization of the second monomer.
- Gao, Haifeng,Tsarevsky, Nicolay V.,Matyjaszewski, Krzysztof
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- DNA polyplexes formed using PEGylated biodegradable hyperbranched polymers
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A novel PEGylated biodegradable hyperbranched PEG-b-PDMAEMA has been synthesized. The low toxicity, small molecular weight PDMAEMA chains were crosslinked using a biodegradable disulfide-based dimethacrylate (DSDMA) agent to yield higher molecular weight hyperbranched polymers. PEG chains were linked onto the polymer surface, masking the positive charge (as shown by Zeta potential measurements) and reducing the toxicity of the polymer. The hyperbranched structures were also cleaved under reducing conditions and analyzed, confirming the expected component structures. The hyperbranched polymer was mixed with DNA and efficient binding was shown to occur through electrostatic interactions. The hyperbranched structures could be reduced easily, generating lower toxicity oligomer chains. (Chemical Presented).
- Tao, Lei,Chou, William C.,Tan, Beng H.,Davis, Thomas P.
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- Combining atom transfer radical polymerization and disulfide/thiol redox chemistry: A route to well-defined (bio)degradable polymeric materials
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Linear well-defined degradable polymethacrylates with internal disulfide link were prepared by atom transfer radical polymerization (ATRP) of methyl, terf-butyl, and benzyl methacrylate using bis[2-(2-bromoisobutyryloxy)ethyl] disulfide as the initiator and CuBr/2,2'-bipyridine as the catalyst at 50°C. The disulfide bond was cleaved to thiol by reduction with tributylphosphine, yielding polymers of half the molecular weight of the starting materials. Degradable gels were prepared by the copolymerization of methyl methacrylate and a disulfide-containing difunctional methacrylate, bis(2-methacryloyloxyethyl) disulfide, using similar reaction conditions. The produced gels were reduced with tributylphosphine to form soluble, low molecular weight linear polydnethyl methacrylate) fragments containing thiol groups at the chain end and along the backbone, originating from the disulfide difunctional initiator and monomer, respectively. The disulfide-cross-linked gels were further used as "supennacroinitiators" for the bulk ATRP of styrene at 90°C, employing CuBr/N,N,N'N'',N''-pentamethyldiethylenetriamine as the catalyst. The length of the polystyrene pendant chains could be controlled by varying the reaction time. The prepared gels with segmented structure swelled more than the starting polymethacrylate gels in both THF and toluene. Degradation experiments confirmed the high degree of chain-end bromine functionalization of the "supermacroinitiators".
- Tsarevsky, Nicolay V.,Matyjaszewski, Krzysztof
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- Cytoplasmic delivery of functional siRNA using pH-Responsive nanoscale hydrogels
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The progress of short interfering RNA (siRNA) technologies has unlocked the development of novel alternatives for the treatment of a myriad of diseases, including viral infections, autoimmune disorders, or cancer. Nevertheless, the clinical use of these therapies faces significant challenges, mainly overcoming the charged and large nature of these molecules to effectively enter the cell. In this work, we developed a cationic polymer nanoparticle system that is able to load siRNA due to electrostatic interactions. The pH-responsiveness and membrane-disrupting ability of these carriers make them suitable intracellular delivery vehicles. In the work presented herein we synthesized, characterized, and evaluated the properties of nanoparticles based on 2-diethylaminoethyl methacrylate and tert-butyl methacrylate copolymers. A disulfide crosslinker was incorporated in the nanogels to enable the degradation of the nanoparticles in reductive environments, showing no significant changes on their physicochemical properties. The capability of the developed nanogels to be internalized, deliver siRNA, and induce gene knockdown were demonstrated using a human epithelial colorectal adenocarcinoma cell line. Overall, these findings suggest that this platform exhibits desirable characteristics as a potential siRNA-delivery platform.
- Liechty, William B.,Scheuerle, Rebekah L.,Vela Ramirez, Julia E.,Peppas, Nicholas A.
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- Novel redox-responsive nanogels based on poly(ionic liquid)s for the triggered loading and release of cargos
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The unique disulfide chemistry has been widely explored for novel and versatile delivery systems addressing both intracellular and extracellular barriers. In this study, novel redox-responsive nanogels were fabricated by radical copolymerization of ionic liquid (IL)-based monomers, 1,n-butanediyl-3,3′-bis-1-vinylimidazolium dibromide ([CnVIm]Br, n = 4, 6), and disulphide dimethacrylate (DSDMA) in selective solvents. The as-synthesized nanogels were characterized using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analyses (TG), dynamic laser scattering (DLS) and zeta (ζ)-potential measurements. The results demonstrated that the sizes of poly(ionic liquid) (PIL)-based nanogels can be tuned by the feed ratio of the monomers and DSDMA. Moreover, the redox-response performances of these nanogels were evaluated through the size variation in the presence of dithiothreitol (DTT) and benzoyl peroxide (BPO). The capability of PIL-based nanogels for controlled release was also investigated by using rhodamine B (RhB) as prototype model drug. It was found that DTT-triggered release of RhB could be achieved. Therefore, a redox-triggered loading and release matrix can be conveniently fabricated via PIL-based nanogels. And it can also be potentially used as a controlled carrier in biological medicine.
- Miao, Congcong,Li, Feng,Zuo, Yong,Wang, Rongmin,Xiong, Yubing
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- DELIVERY OF SMALL INTERFERING RNA AND MICRO RNA THROUGH MEMBRANE-DISRUPTIVE, RESPONSIVE NANOSCALLE HYDROGELS
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Nanoscale, pH-responsive polycationic networks useful for the delivery of anionic biologic therapeutics and associated methods.
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Paragraph 156 - 159
(2014/05/07)
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- The reverse of polymer degradation: In situ crosslinked gel formation through disulfide cleavage
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In contrast to the usual inclusion of disulfide bonds within a polymer structure to facilitate bio-degradation, we have designed a self-curing "one pot" hyperbranched polymer capable of forming crosslinked gels under reducing conditions abundant in tumoural tissue.
- Saeed, Aram O.,Newland, Ben,Pandit, Abhay,Wang, Wenxin
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supporting information; experimental part
p. 585 - 587
(2012/02/05)
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- Functional, star polymeric molecular carriers, built from biodegradable microgel/nanogel cores
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Acid and disulfide biodegradable cross-linkers have been employed to generate microgel star polymers, using RAFT-polymer arms. RAFT end-groups were then exploited to attach functional compounds via both thiol-ene and thiol-pyridyl disulfide exchange reactions.
- Syrett, Jay A.,Haddleton, David M.,Whittaker, Michael R.,Davis, Thomas P.,Boyer, Cyrille
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supporting information; experimental part
p. 1449 - 1451
(2011/03/19)
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- HOLLOW MICROPARTICLES
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The invention provides a process for making hollow microparticles. The process comprises providing a dispersion having a continuous aqueous phase and a discontinuous organic phase and polymerising a monomer in the dispersion to form hollow polymeric microparticles. The continuous aqueous phase of the dispersion comprises a stabiliser and the discontinuous organic phase of the dispersion comprises the monomer and an organic liquid. The monomer has two or more polymerisable groups per molecule. Prior to the step of polymerising the monomer, the discontinuous organic phase does not contain a polymer.
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- NANOPARTICLE COMPOSITIONS FOR CONTROLLED DELIVERY OF NUCLEIC ACIDS
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Micro- and nano-particles are molded in micro- and nano-scale molds fabricated from non-wetting, low surface energy polymeric materials. The micro- and nano-particles can include pharmaceutical compositions, biologic drugs, drug compositions, organic materials, RNA, DNA, oligonucleotides, and the like.
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Page/Page column 49-50; 66-67
(2008/06/13)
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