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Johan F.j. Engbersen - One of the best experts on this subject based on the ideXlab platform.
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Multilayered Thin Films from Boronic Acid-Functional Poly(Amido Amine)s
Pharmaceutical 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
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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.
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Physicochemical and Biological Evaluation of siRNA Polyplexes Based on PEGylated Poly(Amido Amine)s
Pharmaceutical Research, 2012Co-Authors: Pieter Vader, Gert Storm, Johan F.j. Engbersen, 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 .
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Optimization of poly(Amido Amine)s as vectors for siRNA delivery
Journal of controlled release : official journal of the Controlled Release Society, 2010Co-Authors: L.j. Van Der Aa, Pieter Vader, Gert Storm, Raymond M. Schiffelers, Johan F.j. EngbersenAbstract:By Michael addition polymerization of N,N'-cystAminebisacrylamide (CBA) with variable ratios of 4-amino-1-butanol (ABOL) and ethylene diAmine (EDA) or triethylenetetrAmine (TETA), poly(Amido Amine) copolymers could be obtained with tunable charge densities. The copolymers were optimized to serve as nonviral vectors in RNA interference (RNAi) to form stable, nanosized polyplexes with siRNA with maximum transfection efficacy. It was observed that at least 20–30% EDA or TETA amino units in the copolymers is necessary to encapsulate siRNA into small and stable polyplexes (< 200 nm). Incorporation of higher amounts of EDA or TETA in the copolymers did not further improve polyplex formation and stability, but the increased cationic charge in these copolymers resulted in increased cytotoxicity and hemolytic activity. Copolymers with 20% EDA showed excellent gene silencing properties in vitro (70% luciferase knockdown in H1299 cells) with negligible cytotoxicity
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Effect of chemical functionalities in poly(Amido Amine)s for non-viral gene transfection
Journal of controlled release : official journal of the Controlled Release Society, 2008Co-Authors: Chao Lin, Johan F.j. EngbersenAbstract:The development of safe and efficient gene delivery vectors is an essential prerequisite for successful gene therapy. As viral vectors suffer from inherent disadvantages, cationic polymers as non-viral vectors have great potential in gene delivery, but their practical application so far is seriously hampered due to their relatively low transfection efficiency caused by multiple extra- and intracellular gene delivery barriers. Therefore, it is important to provide cationic polymers with functionalities that can seriously influence polymeric properties which are important to overcome gene delivery barriers. In this paper, we aim to contribute to the understanding of the effect of functionalities in cationic polymers on their gene delivery properties and transfection activity. As poly(Amido Amine)s can be easily provided with a large variety of chemical functionalities, we have focused on this class of cationic polymers. It is shown that various structural characteristics in these peptidomimetic polymers such as charge density, rigidity, basicity, hydrophilicity/hydrophobicity, degradability and type of amino groups influence one or more gene delivery properties such as DNA binding capability, colloidal stability, endosomal escape (buffer capacity), vector unpacking, cytotoxicity, and eventual transfection efficiency. Optimal combination of the functionalities in the poly(Amido Amine)s may lead to significant increase of the level of gene expression. This indicates that multifunctionalized polymers like the poly(Amido Amine)s can evolve to the next generation of non-viral gene delivery system for gene therapy.
Jan Feijen - One of the best experts on this subject based on the ideXlab platform.
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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
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Bioreducible poly(Amido Amine)s for gene delivery to ovarian cancer cells
Journal 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).
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Poly(Amido Amine)s as Gene Delivery Vectors: Effects of Quaternary Nicotinamide Moieties in the Side Chains
ChemMedChem, 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.
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novel bioreducible poly Amido Amine s for highly efficient gene delivery
Bioconjugate Chemistry, 2007Co-Authors: Zhiyuan Zhong, Xulin Jiang, Wim E Hennink, Jan Feijen, Johan F.j. EngbersenAbstract:A series of novel bioreducible poly(Amido Amine)s containing multiple disulfide linkages (SS-PAAs) were synthesized and evaluated as nonviral gene vectors. These linear SS-PAAs could be easily obtained by Michael-type polyaddition of various primary Amines to the disulfide-containing cystAmine bisacrylamide. The SS-PAA polymers are relatively stable in medium mimicking physiological conditions (pH 7.4, 150 mM PBS, 37 °C), but are rapidly degraded in the presence of 2.5 mM DTT, mimicking the intracellular reductive environment (pH 7.4, [R−SH] = 5 mM, 37 °C). The polymers efficiently condense DNA into nanoscaled ( +20 mV) polyplexes that are stable under neutral conditions but are rapidly destabilized in a reductive environment, as was revealed by both dynamic light scatting measurement and agarose gel assays. Moreover, most of the poly(Amido Amine)s possess buffer capacities in the pH range pH 7.4−5.1 that are even higher than polyethylenimine (pEI), a property that may favorably contribute to the endosomal escape of the polyplexes. Polyplexes of four of the seven SS-PAAs studied were able to transfect COS-7 cells in vitro with transfection efficiencies significantly higher than those of branched pEI, being one of the most effective polymeric gene carriers reported to date. Importantly, also in the presence of serum, a high level of gene expression could be observed when the incubation time was elongated from 1 h to 4 h. XTT assays showed that SS-PAAs and their polyplexes possess essentially no or only very low cytotoxicity at concentrations where the highest transfection activity is observed. The results indicate that bioreducible poly(Amido Amine)s have excellent properties for the development of highly potent and nontoxic polymeric gene carriers.
Toyoko Imae - One of the best experts on this subject based on the ideXlab platform.
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Selective capture of CO2 by poly(Amido Amine) dendrimer-loaded organoclays
RSC 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.
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Network of sodium hyaluronate with nano-knots junction of poly(Amido Amine) dendrimer
Carbohydrate 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.
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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.
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Adsorption behaviors of poly(Amido Amine) dendrimers with an azacrown core and long alkyl chain spacers on solid substrates.
Journal of colloid and interface science, 2005Co-Authors: Masaki Ujihara, Toyoko ImaeAbstract:Abstract Adsorption behaviors of functional poly(Amido Amine) dendrimers with an azacrown core and long alkyl chain spacers were investigated on gold and self-assembled monolayer (SAM) by means of time course attenuated total reflection–surface enhanced infrared absorption and surface plasmon resonance spectroscopies. While 1.5th and 2.5th generation (G1.5 and G2.5) ester-terminated dendrimers were slightly adsorbed on all substrates exAmined, the adsorption of G2 Amine-terminated dendrimer increased in the order dodecanethiol SAM
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Synthesis and Assembly of Amphiphilic Tadpole-Shaped Block Copolymers Based on Poly(Amido Amine) Dendrimer
Polymer Journal, 1999Co-Authors: Keigo Aoi, Kaname Tsutsumiuchi, Masahiko Okada, Aki Motoda, Mayuko Ohno, Toyoko ImaeAbstract:A concept of “three-dimensional space architectures” by dendrimer-based nano-organized systems having “inter- and intradendrimer cavities” linked with each other through an peripheral array of tailor- made surface substituents with controlled permeability was presented from the standpoint of utilization of amphiphilic dendrimers. As a systematic study on macromolecular design of amphiphilic dendrimers, two tadpole-shaped block copolymers, AB-type linear polymer/dendrimer block copolymers, were synthesized by two different synthetic methodologies. A novel amphiphilic surface-N-hexylamide-type poly(Amido Amine) (PAMAM) dendrimer (generation 2.5) / polysarcosine (poly(N-methylglycine)) block copolymer 4 was synthesized by living ring-opening polymerization of sarcosine N-carboxyanhydride initiated with a core-monofunctional PAMAM dendrimer. An aqueous solution of poly(2-methyl-2-oxazoline)-block-poly(Amido Amine) dendrimer (9) (generation 3.5, 4.5, and 5.5), prepared by divergent dendrimer construction from ω-end-functionalized polyoxazoline, showed critical micelle concentrations (CMCs). The CMC values decrease as the generation of the dendrimer increases, which means that the large globular dendrimer with a strong hydrophilic polyoxazoline linear tail tends to gather on the air/water interface more efficiently than the copolymer having the small oblate dendritic block. Small angle neutron scattering (SANS) investigations of a D2O solution of the dendrimer-containing block copolymer 9 (G=5.5) suggested formation of a spherically assembled mesoscopic structure of 54 nm diameter with an aggregation number of ca. 2.4×103, while the diameter of the dendritic block was estimated to be 3.2 nm.
Jos M. J. Paulusse - One of the best experts on this subject based on the ideXlab platform.
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Multilayered Thin Films from Boronic Acid-Functional Poly(Amido Amine)s
Pharmaceutical 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
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Multilayered Thin Films from Boronic Acid-Functional Poly(Amido Amine)s As Drug-Releasing Surfaces.
Pharmaceutical research, 2015Co-Authors: Sry D. Hujaya, Johannes F.j. Engbersen, Jos M. J. PaulusseAbstract:Purpose To evaluate the potential of poly(Amido Amine)-based multilayered thin films in surface mediated drug release.
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Multilayered Thin Films from Boronic Acid-Functional Poly(Amido Amine)s.
Pharmaceutical research, 2015Co-Authors: Sry D. Hujaya, Johannes 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.
Johannes F.j. Engbersen - One of the best experts on this subject based on the ideXlab platform.
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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
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Multilayered Thin Films from Boronic Acid-Functional Poly(Amido Amine)s As Drug-Releasing Surfaces.
Pharmaceutical research, 2015Co-Authors: Sry D. Hujaya, Johannes F.j. Engbersen, Jos M. J. PaulusseAbstract:Purpose To evaluate the potential of poly(Amido Amine)-based multilayered thin films in surface mediated drug release.
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Multilayered Thin Films from Boronic Acid-Functional Poly(Amido Amine)s.
Pharmaceutical research, 2015Co-Authors: Sry D. Hujaya, Johannes 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.
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Bioreducible poly(Amido Amine)s for gene delivery to ovarian cancer cells
Journal 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).