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Johan F.j. Engbersen – One of the best experts on this subject based on the ideXlab platform.
Multilayered Thin Films from Boronic Acid-Functional Poly(Amido Amine)sPharmaceutical Research, 2015Co-Authors: Sry D. Hujaya, Johan F.j. Engbersen, Jos M. J. PaulusseAbstract:
Purpose To investigate the properties of phenylboronic acid-functional poly(Amido Amine) polymers (BA-PAA) in forming multilayered thin films with poly(vinyl alcohol) (PVA) and chondroitin sulfate (ChS), and to evaluate their compatibility with COS-7 cells. Methods Copolymers of phenylboronic acid-functional poly(Amido Amine)s, differing in the content of primary Amine (DAB-BA-PAA) or alcohol (ABOL-BA-PAA) side groups, were synthesized and applied in the formation of multilayers with PVA and ChS. Biocompatibility of the resulting films was evaluated through cell culture experiments with COS-7 cells grown on the films. Results PVA-based multilayers were thin, reaching ~100 nm at 10 bilayers, whereas ChS-based multilayers were thick, reaching ~600 nm at the same number of bilayers. All of the multilayers are stable under physiological conditions in vitro and are responsive to reducing agents, owing to the presence of disulfide bonds in the polymers. PVA-based films were demonstrated to be responsive to glucose at physiological pH at the investigated glucose concentrations (10–100 mM). The multilayered films displayed biocompatibility in cell culture experiments, promoting attachment and proliferation of COS-7 cells. Conclusions Responsive thin films based on boronic acid functional poly(Amido Amine)s are promising biocompatible materials for biomedical applications, such as drug releasing surfaces on stents or implants. Graphical Abstract Layer-by-Layer Assembly
Intercalating quaternary nicotinamide-based poly(Amido Amine)s for gene delivery.Journal of Controlled Release, 2014Co-Authors: L.j. Van Der Aa, Pieter Vader, Gert Storm, Raymond M. Schiffelers, Johan F.j. EngbersenAbstract:
In the development of potent polymeric gene carriers for gene therapy, a good interaction between the polymer and the nucleotide is indispensable to form small and stable polyplexes. Polymers with relatively high cationic charge density are frequently used to provide these interactions, but high cationic charge is usually associated with severe cytotoxicity. In this study an alternative, nucleotide specific binding interaction based on intercalation was investigated to improve polymer/pDNA complex formation. For this purpose bioreducible poly(Amido Amine) copolymers (p(CBA-ABOL/Nic)) were synthesized with different degrees of intercalating quaternary nicotinamide (Nic) groups and amide-substituted derivatives in their side chains. The quaternary nicotinamide group was chosen as intercalating moiety because this group is part of the naturally occurring NAD+ coenzyme and is therefore expected to be non-toxic and non-carcinogenic. The presence of the quaternary nicotinamide moieties in the poly(Amido Amine) copolymers showed to effectively promote self-assembled polyplex formation already at low polymer/DNA ratios and results in decreased polyplex size and increased stability of the polyplexes. Furthermore, in contrast to the primary Amine functionalized analogs the quaternary nicotinamide polymers showed to be non-hemolytic, indicating their compatibility with cell membranes. Polymers with 25% of Nic in the side chains induced GFP expressions of about 4–5 times that of linear PEI, which is comparable with p(CBA-ABOL), the parent PAA without Nic, but at a two- to fourfold lower required polymer dose. N-phenylation of the nicotinamide functionality even further reduces the required polymer dose to form stable polyplexes, which is a major improvement for these kinds of cationic polymers.
Physicochemical and Biological Evaluation of siRNA Polyplexes Based on PEGylated Poly(Amido Amine)sPharmaceutical Research, 2012Co-Authors: Pieter Vader, Johan F.j. Engbersen, Gert Storm, Raymond M. SchiffelersAbstract:
Purpose Use of RNA interference as novel therapeutic strategy is hampered by inefficient delivery of its mediator, siRNA, to target cells. Cationic polymers have been thoroughly investigated for this purpose but often display unfavorable characteristics for systemic administration, such as interactions with serum and/or toxicity. Methods We report the synthesis of a new PEGylated polymer based on biodegradable poly(Amido Amine)s with disulfide linkages in the backbone. Various amounts of PEGylated polymers were mixed with their unPEGylated counterparts prior to polyplex formation to alter PEG content in the final complex. Results PEGylation effectively decreased polyplex surface charge, salt- or serum-induced aggregation and interaction with erythrocytes. Increasing amount of PEG in formulation also reduced its stability against heparin displacement, cellular uptake and subsequent silencing efficiency. Yet, for polyplexes with high PEG content, significant gene silencing efficacy was found, which was combined with almost no toxicity. Conclusions PEGylated poly(Amido Amine)s are promising carriers for systemic siRNA delivery in vivo .
Jan Feijen – One of the best experts on this subject based on the ideXlab platform.
Poly(Amido Amine)s Containing Agmatine and Butanol Side Chains as Efficient Gene Carriers.Macromolecular bioscience, 2015Co-Authors: Young-wook Won, Johannes F.j. Engbersen, Jan Feijen, Martinus J.k. Ankone, Sung Wan KimAbstract:
A new type of bioreducible poly(Amido Amine) copolymer is synthesized by the Michael addition polymerization of cystAmine bisacrylamide (CBA) with 4-aminobutylguanidine (agmatine, AGM) and 4-aminobutanol (ABOL). Since the positively charged guanidinium groups of AGM and the hydroxybutyl groups of ABOL in the side chains have shown to improve the overall transfection efficiency of poly(Amido Amine)s, it is hypothesized that poly(CBA-ABOL/AGM) synthesized at the optimal ratio of both components would result in high transfection efficiency and minimal toxicity. In this study, a series of the poly(CBA-ABOL/AGM) copolymers is synthesized as gene carriers. The polymers are characterized and luciferase transfection efficiencies of the polymers in various cell lines are investigated to select the ideal ratio between AGM and ABOL. The poly(CBA-ABOL/AGM) containing 80% AGM and 20% ABOL has shown the best transfection efficiency with the lowest cytotoxicity, indicating that this polymer is very promising as a potent and nontoxic gene carrier
Bioreducible poly(Amido Amine)s for gene delivery to ovarian cancer cellsJournal of Controlled Release, 2008Co-Authors: Chao Lin, Zhiyuan Zhong, Jan Feijen, Martin C. Lok, Holger K. De Wolf, W.e. Hennink, Johannes F.j. EngbersenAbstract:
Bioreducible poly(Amido Amine)s (SS-PAAs) with different groups in the side chain were evaluated for gene delivery to ovarian cancer cells, both in vitro and in vivo after intraperitoneal administration in mice bearing an ovarian cancer xenograft. Polyplexes of SS-PAAs with e.g. hydroxybutyl or hydroxypentyl side groups induce much higher transfection in vitro than polyplexes of branched pEI (25 kDa) as a positive control. The in vivo transfection efficiency of polyplexes of SS-PAA with hydroxybutyl side groups is similar to that of linear pEI (22 kDa).
Poly(Amido Amine)s as Gene Delivery Vectors: Effects of Quaternary Nicotinamide Moieties in the Side ChainsChemMedChem, 2008Co-Authors: Miguel A. Mateos-timoneda, Jan Feijen, Wim E Hennink, Martin C. Lok, Johan F.j. EngbersenAbstract:
To evaluate the effect of quaternary nicotinamide pendant groups on gene delivery properties, a series of poly(Amido Amine) (co)polymers were synthesized by Michael addition polymerization of N, N-cystAminebisacrylamide with variable ratios of 1-(4-aminobutyl)-3-carbamoylpyridinium (Nic-BuNH2), and tert-butyl-4-aminobutyl carbamate (BocNH-BuNH2), yielding poly(Amido Amine)s (NicX-NHBoc) with X=0, 10, 30, and 50 % of quaternary nicotinamide groups in the polymer side chains. Deprotection of the pendant Boc-NH groups afforded an analogous series of polymers (NicX-NH2) with higher charge density (due to the presence of protonated primary amino groups in the side chains) and subsequent acetylation yielded a series of polymers (NicX-NHAc) of lower hydrophobicity than the Boc-protected polymers. The polymers with the Boc-protected or the acetylated amino groups showed high buffer capacity in the range pH 5.1-7.4, which is a property that can contribute to endosomal escape of polyplexes. The presence of quaternary nicotinamide groups has distinct beneficial effects on the gene vector properties of these polymers. The polymers containing 30 % of quaternary nicotinamide groups in their side chains condense DNA into small, nanosized particles (200 nm) with positive surface charge (+15 mV). Fluorescence experiments using ethidium bromide as a competitor showed that the quaternary nicotinamide groups intercalate with DNA, contributing to a more intimate polymer-DNA binding and shielding. Polyplexes of nicotinamide-functionalized poly(Amido Amine)s NicX-NHBoc and NicX-NHAc, formed at 12/1 polymerDNA mass ratio, efficiently transfect COS-7 cells with efficacies up to four times higher than that of PEI (Exgen 500), and with essentially absence of cytotoxicity. NicX-NH2 polymers, possessing protonated primary amino groups in their side chains, have a higher cytotoxicity profile under these conditions, but at lower 3/1 polymer-DNA mass ratio also these polymers are capable of efficient transfection, while retaining full cell viability.
Toyoko Imae – One of the best experts on this subject based on the ideXlab platform.
Selective capture of CO2 by poly(Amido Amine) dendrimer-loaded organoclaysRSC Advances, 2015Co-Authors: Kinjal J. Shah, Toyoko Imae, Atindra D. ShuklaAbstract:
Clay loaded poly(Amido Amine) dendrimers were explored for capture and storage of CO2. The loading of dendrimer was promotive in the order of laponite > hydrotalcite > sericite and depended on the surface area of the clays. The CO2 adsorption on organoclays of laponite and sericite with cationic dendrimer increased with the amount of loaded dendrimer. While CO2 on pristine laponite was completely released in the desorption process, CO2 on organo laponite remained in part after the desorption equilibrium. Since the removal of CO2 from organo laponite was almost comparable to that from pristine clay, it can be mentioned that CO2 adsorbed on the binding site of laponite is almost desorbed but CO2 on the binding site of dendrimer is conserved in organoclay. In contrast, in the case of the CO2 adsorption on the organoclay of hydrotalcite with an anionic dendrimer, the diminution of adsorption sites on hydrotalcite owing to the occupation by dendrimer was observed. It can be mentioned that the cation-exchanged organo laponite loaded Amine-terminated dendrimer is a valuable solid adsorbent with a highly selective capture capacity for CO2.
Network of sodium hyaluronate with nano-knots junction of poly(Amido Amine) dendrimerCarbohydrate Polymers, 2012Co-Authors: Toyoko Imae, Shin-ichi HamaguchiAbstract:
Abstract Amine-terminated poly(Amido Amine) (PAMAM) dendrimers have been attached to sodium hyaluronates (NaHAs) by a coupling reaction. The morphology of NaHAs was varied from the common network to the bead & string network, which gave rise to the decrease in viscosity of NaHAs. The bead & string network was more abundant for the covalent network complex than the noncovalent one. The beads, that is, the nano-knots of the network consist of the covalent-bonded NaHA/dendrimer composites, and the strings are NaHA chains. Beads became small and strings decreased in number with decreasing a molecular weight of NaHA. The complexation of sodium poly- l -glutamates (NaPGAs) with PAMAM dendrimers was different in the manner from that of NaHAs with dendrimers. Flexible NaPGAs produced globular composites with dendrimers.
Self-assembled monolayer of carboxyl-terminated poly(Amido Amine) dendrimer.Journal of nanoscience and nanotechnology, 2006Co-Authors: Masahiro Ito, Toyoko ImaeAbstract:
Adlayer formation and adsorption structure of 2.5th-generation poly(Amido Amine) dendrimer with carboxyl-terminated groups on solid substrates were investigated by atomic force microscopy, surface plasmon resonance spectroscopy, and surface enhanced infrared absorption spectroscopy. Dendrimer molecules are not uniformly adsorbed on solid surface but form aggregates with a width of approximately 100 nm and a height less than 1 nm. Adsorption reaches in equilibrium at 100-1000 sec, depending on the dendrimer concentration. The adsorption-desorption process is considerably reproducible and repeatable. Although the adsorption at equilibrium increases with dendrimer concentration and reaches maximum at neutral pH, monolayer is always maintained after the desorption with solvent. This indicates the formation of self-assembled monolayer. Such monolayer is preserved even at the variation of pH. Although most carboxylates are protonated at acidic pH, small amount of carboxylate remains even at acidic pH. The adsorption structure of dendrimer was illustrated.