Poly Propylene Imine Dendrimers Research Articles

A cleaner and eco-benign process for wool dyeing with madder, Rubia tinctorum L., root natural dye

In this study, an alternative cleaner process over traditional metallic mordanting process for wool dyeing with madder, Rubia tinctorum L., root natural dye was presented. Wool surface was modified with novel eco-friendly and biocompatible cationizing agent having numerous free amine groups, namely chitosan–polypropylene imine dendrimer hybrid (CS-PPI). Modified wool demonstrated remarkable increase in dye uptake as compared to raw wool. Optimal dyeing results were obtained when CS-PPI 7 %, madder dye 20 % and dyeing pH 7 were employed. Dyeing results such as percent dye exhaustion and color depth emphasized auxiliary agents, i.e., metallic mordant and acid could be eliminated from wool dyeing process with madder dye. Saturation point shifted to lower dye concentrations in the treated wool suggested the same color depth could be obtained using lower amount of crude dye material. Wool modification with CS-PPI demonstrated no adverse impact on other properties such as colorfastness and color shade characteristics. In addition, treated wool exhibited excellent antimicrobial activity (nearly 100 % microbial reduction) against two common pathogenic microorganisms, Escherichia coli and Staphylococcus aureus which were almost durable after dyeing and subsequent repeated washes. In general, the results of this investigation showed that CS-PPI can be employed as an alternative eco-friendly “bio-mordant” as well as effective antimicrobial finishing material in wool dyeing with madder dye.

Differences in toxicity of anionic and cationic PAMAM and PPI dendrimers in zebrafish embryos and cancer cell lines

Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96h and human cancer cell lines for 24h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, with EC50 values ranging from 0.16 to just below 1.7μM at 24 and 48hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values≥402μM (PAMAMs) and ≤240μM (PPIs) for HepG2 and ≤13.24μM (PAMAMs) and ≤12.84μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos.

Development and characterization of surface engineered PPI dendrimers for targeted drug delivery

In this study, we reported folate-conjugated polypropylene imine dendrimers (FA–PPI) as efficient carrier for model anticancer drug, methotrexate (MTX), for pH-sensitive drug release, selective targeting to cancer cells, and anticancer activity. In the in vitro drug release studies this nanoconjugate of MTX showed initial rapid release followed by gradual slow release, and the drug release was found to be pH sensitive with greater release at acidic pH. The ex vivo investigations with human breast cancer cell lines, MCF-7, showed enhanced cytotoxicity of MTX–FA–PPI with significantly enhanced intracellular uptake. The biofate of nanoconjugate was determined in Wistar rat where MTX–FA–PPI showed 37.79-fold increase in the concentration of MTX in liver after 24 h in comparison with free MTX formulation.

Structural effects on cosolubilization of dendrimer and propofol in water dilutable microemulsions as delivery vehicle

In this study we characterized a new and improved transport vehicle for 2,6-diisopropylphenol (propofol), a hydrophobic anesthesia drug, in the absence and presence of dendrimers being a transporting agents across cells, polypropylenimine (PPI) dendrimer generation 2 (PPI-G2) into a microemulsion (ME). Three unique systems of water-dilutable compositions capable of inverting from W/O to bicontinuous and to O/W structures upon water dilutions were studied by means of electrical conductivity, electron paramagnetic resonance (EPR), and self-diffusion nuclear magnetic resonance (SD-NMR). The microviscosity, as well as the order parameter (from EPR results) increase with the increase in the dendrimer content, while inverting the structures from W/O to bicontinuous ME. Inversion from the bicontinuous mesophase to the O/W nanodroplets caused a very minor increase in the order parameter. Self-diffusion NMR measurements provided information on the diffusivity and the interactions of the different components of the ME. It was found that propofol has no effect on the diffusivity of the components since it is embedded within the core of the ME droplets. However, the dendrimer increases the diffusivity of water. In addition, we learned that at high dendrimer content, it remains solubilized; however its location at the ME/water interface moves to the water continuous phase. The study demonstrates the ability of water dilutable MEs to act as drug carriers hosting both propofol and dendrimer.

One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell.

Gene therapies represent a promising therapeutic route for liver cancers, but major challenges remain in the design of safe and efficient gene-targeting delivery systems. For example, cationic polymers show good transfection efficiency as gene carriers, but are hindered by cytotoxicity and non-specific targeting. Here we report a versatile method of one-step conjugation of glycyrrhetinic acid (GA) to reduce cytotoxicity and improve the cultured liver cell -targeting capability of cationic polymers. We have explored a series of cationic polymer derivatives by coupling different ratios of GA to polypropylenimine (PPI) dendrimer. These new gene carriers (GA-PPI dendrimer) were systematically characterized by UV-vis,1H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, confocal microscopy and flow cytometry. We demonstrate that GA-PPI dendrimers can efficiently load and protect pDNA, via formation of nanostructured GA-PPI/pDNA polyplexes. With optimal GA substitution degree (6.31%), GA-PPI dendrimers deliver higher liver cell transfection efficiency (43.5% vs 22.3%) and lower cytotoxicity (94.3% vs 62.5%, cell viability) than the commercial bench-mark DNA carrier bPEI (25kDa) with cultured liver model cells (HepG2). There results suggest that our new GA-PPI dendrimer are a promising candidate gene carrier for targeted liver cancer therapy.

A study of dendritic ionic liquid crystals: Using (S)-4-citronellyloxybenzoic acid and polypropylene imine dendrimers

In order to investigate the relationship between macromolecular structures and mesomorphic properties; dendritic ionic liquid crystals have been synthesized either by conventional method or microwave assisted synthesis technique and characterized by spectroscopic methods (FT-IR, 1H-NMR, 13C-NMR). Polypropylene-imine (PPI) dendrimers based on diaminobutane (DAB) having increasing number of amino terminal groups (DABn; n=4, 8, 16, 32) were interacted with (S)-4-citronellyloxybenzoic acid (S-CBA) which already possessed liquid crystal property. These interactions were accomplished either by sonification to obtain quaternary ammonium salt or covalently linked by using appropriate coupling reagent. The liquid crystalline properties of the dendritic molecules were investigated by differential scanning calorimetry (DSC) and polarizing optical microscopy (POM). Thermal stability was studied by Thermal Gravimetric Analysis (TGA). Synthesized ion complexes showed a non-tilted smectic mesophase with wider mesomorphic range than that of single mesogenic unit, whereas those derivatives generated by covalent linkage exhibited no mesomorphism.

Antimicrobial Activities of the Polypropylene Imine Dendrimer Aginst Bacteria Isolated From Rural Water Resources

Background: Dendrimers are a new class of polymeric materials with the well-defined structure, composition and architecture. Owing to antibacterial properties of dendrimers, they can be used as alternative water and wastewater disinfection with the minimum adverse side effects. Objectives: The aim of the present study was to evaluate the antibacterial activity of second generation poly propylene imine (PPI- G2) dendrimer on predominant bacteria in drinking water resources. Materials and Methods: In this qualitative and interventional study, a total of 764 water samples were collected from rural areas in Qom Province, Iran, and bacteria were isolated and identified using standard procedures. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against gram-positive and gram-negative bacteria were determined according to clinical and laboratory standards institute (CLSI) guideline. Standard discs were prepared using different concentrations of dendrimer on Mueller- Hinton agar plates. Results: The most important isolated bacteria were Escherichia coli 37 (48.7%), Klebsiella oxytoca 12 (15.8%), Proteus mirabilis 3 (4%), Entrobacter aerogenes 8 (10.5%), Citrobacter freundii 4 (5.2%), Pseudomonas aeruginosa 5 (6.6%), Staphylococcus aureus 2 (2.6%), and Bacillus subtilis 5 (6.6%). Moreover, it was found that PPI-G2 showed more potent activity towards the gram-positive bacteria than the gram-negative ones. Conclusions: The PPI-G2 dendrimer with end amine groups exhibited a positive impact on the removal of dominant bacterial isolated strains. Therefore, it is possible to use these nanodendrimers as a safe and effective material for water disinfection in the future.

Enhanced gene expression in the brain following intravenous administration of lactoferrin-bearing polypropylenimine dendriplex

The possibility of using gene therapy for the treatment of brain diseases such as brain cancer, Alzheimer's and Parkinson's diseases, is currently hampered by the lack of gene delivery systems able to cross the blood–brain barrier and deliver DNA to the brain following intravenous administration.On the basis that lactoferrin can effectively reach the brain by using specific receptors for crossing the blood–brain barrier, we propose to investigate if a lactoferrin-bearing generation 3-diaminobutyric polypropylenimine (DAB) dendrimer would allow the transport of plasmid DNA to the brain after intravenous administration.In this work, we demonstrated that the conjugation of lactoferrin to the dendrimer led to an enhanced DNA uptake by 2.1-fold in bEnd.3 murine brain capillary endothelial cells compared to the unmodified dendriplex in vitro. In vivo, the intravenous administration of lactoferrin-bearing DAB dendriplex resulted in a significantly increased gene expression in the brain, by more than 6.4-fold compared to that of DAB dendriplex, while decreasing gene expression in the lung and the kidneys. Gene expression in the brain was significantly higher than in any other major organs of the body.Lactoferrin-bearing generation 3 polypropylenimine dendrimer is therefore a highly promising delivery system for systemic gene delivery to the brain.

Activation Effect of Fullerene C60 on the Carbon Dioxide Absorption Performance of Amine-Rich Polypropylenimine Dendrimers.

Converting amine-rich compounds into highly effective carbon dioxide (CO2 ) sorbents requires a better understanding and control of their properties. The reaction of fullerene C60 with polyethyleneimine converts the polymer into a high-performance CO2 sorbent. In this study, experimental evidence is reported for the activation effect of C60 on the amine moieties of the polymer. To do so, polypropylenimine (PPI) dendrimers that allowed for a systematic comparison of molecular composition and CO2 absorption were used. The addition of C60 to PPI to form PPI-C60 results in a reduction of the energy barrier of CO2 absorption, but also in a parallel decrease in the frequency of successful collisions between CO2 and PPI-C60 due to a possible disruption of the hydrogen-bonding network of amino groups and bound water in PPI. This finding supports the existence of a non-affinity "repulsive" effect between hydrophobic C60 and hydrophilic amines that forces them to be actively exposed to CO2.

PEGylation of Polypropylenimine Dendrimer with Alkylcarboxylate Chain Linkage to Improve DNA Delivery and Cytotoxicity.

One of the major limitations of effective nonviral gene carriers is their potential high cytotoxicity. Conjugation of polyethylene glycol (PEG) to polymers is a common approach to decrease toxicity and improve biodistribution. The aim of this study was to evaluate the effect of PEGylation on generation 5 polypropylenimine (PPI) dendrimer by using PEG moieties or alkyl-PEG groups. Polymers were synthesized by grafting of 5 and 10 % primary amines of PPI to NH2-PEG-COOH or Br-(CH2)9-CO-NH-PEG-COOH through Amide bond formation or nucleophilic substitution, respectively. Transfection efficiency and cytotoxicity were analyzed after 4 and 24 h exposure of neuroblastoma cell line (Neuro-2a) with synthesized vectors. Among all of the PEG-PPI derivatives, 5 % PEG-conjugated G5 PPI with alkyl chain (PPI-alkyl-PEG 5 %) resulted in the most efficient gene expression. This vector also significantly decreased the in vitro cytotoxicity and sub-G1 peak in flow cytometry histogram after 24 h incubation. Our results indicate that modification of 5 % primary amines of G5 PPI with PEG using alkyl chain as linker produces a promising vector combining low cytotoxicity, appropriate biodegradability, and high gene transfection efficiency.

Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes

The possibility of using gene therapy for the treatment of cancer is limited by the lack of safe, intravenously administered delivery systems able to selectively deliver therapeutic genes to tumors. In this study, we investigated if the conjugation of the polypropylenimine dendrimer to lactoferrin and lactoferricin, whose receptors are overexpressed on cancer cells, could result in a selective gene delivery to tumors and a subsequently enhanced therapeutic efficacy. The conjugation of lactoferrin and lactoferricin to the dendrimer significantly increased the gene expression in the tumor while decreasing the non-specific gene expression in the liver. Consequently, the intravenous administration of the targeted dendriplexes encoding TNFα led to the complete suppression of 60% of A431 tumors and up to 50% of B16-F10 tumors over one month. The treatment was well tolerated by the animals. These results suggest that these novel lactoferrin- and lactoferricin-bearing dendrimers are promising gene delivery systems for cancer therapy. From the Clinical EditorSpecific targeting of cancer cells should enhance the delivery of chemotherapeutic agents. This is especially true for gene delivery. In this article, the authors utilized a dendrimer-based system and conjugated this with lactoferrin and lactoferricin to deliver anti-tumor genes. The positive findings in animal studies should provide the basis for further clinical studies.

UV-Induced Stable Planar Alignment of Nematic Liquid Crystals Using a Polypropyleneimine Dendrimer Having a Mesogen Consisting of Cinnamate and Azobenzene Moieties

A liquid crystalline dendrimer having a cinnamate mesogen containing an azobenzene moiety (D-6AC2) was prepared as an alignment agent of nematic liquid crystals for a planar homogeneous alignment. D-6AC2 is a thermotropic liquid crystal showing smectic phases. A mixture of ZLI-4792 with 1wt% of D-6AC2 exhibited a homeotropic alignment. After UV irradiation of the same sample, the schlieren texture due to a planar orientation was observed, and the texture was maintained even after 133 days. Thus D-6AC2 can induce the stable planar alignment of NLC upon UV irradiation. Furthermore, D-6AC2 could induce a planar homogeneous alignment by polarized UV light irradiation.

Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy.

We report a novel cancer-targeted nanomedicine platform for imaging and prospect for future treatment of unresected ovarian cancer tumors by intraoperative multimodal phototherapy. To develop the required theranostic system, novel low-oxygen graphene nanosheets were chemically modified with polypropylenimine dendrimers loaded with phthalocyanine (Pc) as a photosensitizer. Such a molecular design prevents fluorescence quenching of the Pc by graphene nanosheets, providing the possibility of fluorescence imaging. Furthermore, the developed nanoplatform was conjugated with poly(ethylene glycol), to improve biocompatibility, and with luteinizing hormone-releasing hormone (LHRH) peptide, for tumor-targeted delivery. Notably, a low-power near-infrared (NIR) irradiation of single wavelength was used for both heat generation by the graphene nanosheets (photothermal therapy [PTT]) and for reactive oxygen species (ROS)-production by Pc (photodynamic therapy [PDT]). The combinatorial phototherapy resulted in an enhanced destruction of ovarian cancer cells, with a killing efficacy of 90%–95% at low Pc and low-oxygen graphene dosages, presumably conferring cytotoxicity to the synergistic effects of generated ROS and mild hyperthermia. An animal study confirmed that Pc loaded into the nanoplatform can be employed as a NIR fluorescence agent for imaging-guided drug delivery. Hence, the newly developed Pc-graphene nanoplatform has the significant potential as an effective NIR theranostic probe for imaging and combinatorial phototherapy.

Preparation of Effective and Safe Gene Carriers by Grafting Alkyl Chains to Generation 5 Polypropyleneimine.

Gene therapy is a novel method to treat a variety of diseases including genetic disorders and cancer. Nonviral gene carriers have now gained considerable attention as gene carrier systems. Polyamidoamine (PAMAM) and polypropyleneimine (PPI) are the two most widely used denderimers in gene delivery studies. The aim of the current study was to investigate the effects of modification of generation 5 polypropyleneimine (G5 PPI) dendrimers with alkanoate groups as hydrophobic moieties on DNA transfection and cytotoxicity. Six, 10, and 16 carbon derivatives of bromoalkanoic acids were conjugated onto PPI with 10%, 30%, and 50% of surface amine grafting. Ethidium bromide exclusion assay results proved the ability of modified carriers to condense DNA. Transfection assay showed higher DNA delivery potential for 30% and 50% grafting with decanoate moieties compared to native G5 PPI and Superfect(TM). 3-(4,5-Dimethylthiazol-2-yl)-2,5-di phenyltetrazolium bromide (MTT) and apoptosis experiments showed lower toxicity for modified carriers compared to unmodified PPI. The hemolytic effect of grafted carriers was not significantly different from G5 PPI. Size and zeta potential measurements revealed that polyplex size was less than 200 nm and electrical charges were in the range 14-25 mV. The hydrophobic modifications improved transfection activity and toxicity of G5 PPI without negatively affecting hemocompatibility. These modified carriers are therefore promising candidates for further in vivo investigations.

Reversal of P-glycoprotein-mediated multidrug resistance by CD44 antibody-targeted nanocomplexes for short hairpin RNA-encoding plasmid DNA delivery

Multidrug resistance (MDR) remains one of the major reasons for the reductions in efficacy of many chemotherapeutic agents in cancer therapy. As a classical MDR phenotype of human malignancies, the adenosine triphosphate binding cassette (ABC)-transporter P-glycoprotein (MDR1/P-gp) is an efflux protein with aberrant activity that has been linked to multidrug resistance in cancer. For the reversal of MDR by RNA interference (RNAi) technology, an U6-RNA gene promoter-driven expression vector encoding anti-MDR1/P-gp short hairpin RNA (shRNA) molecules was constructed (abbreviated pDNA-iMDR1-shRNA). This study explored the feasibility of using Pluronic P123-conjugated polypropylenimine (PPI) dendrimer (P123-PPI) as a carrier for pDNA-iMDR1-shRNA to overcome tumor drug resistance in breast cancer cells. P123-PPI functionalized with anti-CD44 monoclonal antibody (CD44 receptor targeting ligand) (anti-CD44-P123-PPI) can efficiently condense pDNA into nanocomplexes to achieve efficient delivery of pDNA, tumor specificity and long circulation. The in vitro studies methodically evaluated the effect of P123-PPI and anti-CD44-P123-PPI on pDNA-iMDR1-shRNA delivery and P-gp downregulation. Our in vitro results indicated that the P123-PPI/pDNA and anti-CD44-P123-PPI/pDNA nanocomplexes with low cytotoxicity revealed higher transfection efficiency compared with the PPI/pDNA nanocomplexes and Lipofectamine™ 2000 in the presence of serum. The nanocomplexes loaded with pDNA-iMDR1-shRNA against P-gp could reverse MDR accompanied by the suppression of MDR1/P-gp expression at the mRNA and protein levels and improve the internalization and cytotoxicity of Adriamycin (ADR) in the MCF-7/ADR multidrug-resistant cell line. BALB/c nude mice bearing MCF-7/ADR tumor were utilized as a xenograft model to assess antitumor efficacy in vivo. The results demonstrated that the administration of anti-CD44-P123-PPI/pDNA-iMDR1-shRNA nanocomplexes combined with ADR could inhibit tumor growth more efficiently than ADR alone. The enhanced therapeutic efficacy of ADR may be correlated with increased accumulation of ADR in drug-resistant tumor cells. Consequently, these results suggested that the use of pDNA-iMDR1-shRNA-loaded nanocomplexes may be a promising gene delivery strategy to reverse MDR and improve the effectiveness of chemotherapy.

Nano polypropylenimine dendrimer (DAB-PPI-G1): as a novel nano basic-polymer catalyst for one-pot synthesis of 2-amino-2-chromene derivatives

For the first time, a novel nano basic-polymer catalyst for the green synthesis of new 2-amino-2-chromene derivatives, avoiding the use of any metal or acid catalysts, is proposed.

Urea and thiourea modified polypropyleneimine dendrimers clear intracellular α-synuclein aggregates in a human cell line.

Synucleinopathies are neurodegenerative pathologies in which disease progression is closely correlated to brain accumulation of insoluble α-synuclein, a small protein abundantly expressed in neural tissue. Here, two types of modified polypropyleneimine (PPI) dendrimers having either urea or methylthiourea (MTU) surface functional groups were investigated in a cellular model of synucleinopathy. Dendrimers are synthetic macromolecules that may be produced in a range of well-defined molecular sizes. Using cellomics array scan high-content screening, we show that both types of dendrimers are able to significantly reduce intracellular levels of α-synuclein aggregates dependent on the concentration, the type and molecular size of the dendrimer with the bigger size MTU-dendrimers having the highest potency. The intracellular clearance of α-synuclein aggregates by dendrimers was achieved at noncytotoxic concentrations.

Dendrimer functionalized polysilane: An efficient and recyclable organocatalyst

ABSTRACTPolysilane supported dendrimer was efficiently utilized as an organocatalyst for Knoevenagel condensation reaction. Polysilane support was synthesized by the polymerization of trichloromethylsilane. The polypropyleneimine (PPI) dendrimer was grafted on the polymer support by divergent method. The dendrimer was synthesized up to three generations (G3). The dendrimer functionalized polysilane (PS‐PPIG3) was found to contain high concentration of terminal amino groups. The catalytic activity of the PS‐PPIG3 dendrimer was generalized by conducting the Knoevenagel condensation reaction with diverse sets of substrates, and was found to be an efficient organocatalyst. The condensation product could be easily separated from the reaction medium because of the heterogeneous nature of the polymer support. The reaction conditions were optimized, and the catalyst was found to be reusable. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41593.

Combined EPR and Molecular Modeling Study of PPI Dendrimers Interacting with Copper Ions: Effect of Generation and Maltose Decoration

Understanding the early onset of neurodegeneration is crucial to deploy specific treatments for patients before the process becomes irreversible. Copper has been proposed as a biomarker for many neurodegenerative disorders, being the ion released by pathologically unfolded proteins involved in many biochemical pathways. Dendrimers are macromolecules that bind metal ions with a large ion/ligand ratio, thus, allowing a massive collection of copper. This work provides structural information, obtained via molecular modeling and EPR, for the binding sites of copper in polypropyleneimine (PPI) dendrimers, especially in the maltose decorated form that has potential applications in diagnosis and therapies for various types of neurodegenerations. The analysis of the EPR spectra showed that, at the lowest Cu concentrations, the results are well supported by the calculations. Moreover, EPR analysis at increasing Cu(II) concentration allowed us to follow the saturation behavior of the interacting sites identified by the modeling study.

Novel Super Adsorbent Molecules, Carbon Nanotubes Modified by Dendrimer Miniature Structure, for the Removal of Trace Organic Dyes

In this study, multiwalled carbon nanotubes were successfully modified using poly propyleneimine dendrimer. Structural characterization of the newly synthesized adsorbent confirmed the modification of nanotubes by dendrimer molecules. In order to evaluate the performance of this novel adsorbent for the removal of two direct dyes from textile wastewaters, the effect of important parameters including pH, initial dye concentration, adsorbent dosage, and inorganic salts was investigated in single and binary dye solutions. Response surface methodology was employed to find the relation between the effective parameters and dye removal efficiency. The adsorption process was optimized to reach the dye removal of 95% using response optimizer. The prepared adsorbent showed excellent adsorption behavior toward the anionic dye molecules, and the dye removal efficiencies of nanotubes were significantly improved from 17.7% to 99.9% after their modification with dendrimer. Also, the desorption tests revealed the maximum dye release of 44.01%.