Poly Propylene Imine Research Articles

Hyperbranched dendritic nano-carriers for topical delivery of dithranol

The purpose of the current investigation was to explore the potential of polypropylene imine (PPI) dendrimers to deliver dithranol (DIT) topically and to evaluate its encapsulation, permeation and skin irritation potential. PPI (5.0 generation, 5.0 G) dendrimers and DIT-loaded PPI (DIT–PPI) were prepared and characterized by spectroscopy and transmission electron microscopy. DIT encapsulation, in vitro skin permeation study, skin irritation studies, fluorescent studies and tape stripping studies were performed. Loading of DIT was found to be pH dependent with maximum encapsulation at acidic pH (1.0 ± 0.02, 17.2 ± 0.56 and 57.1 ± 1.32% at 7.4, 5.5 and 1.2 pH, respectively). DIT–PPI showed significantly enhanced permeation rate constant and lesser skin irritation (11.61 ± 1.80 μg/cm2/h and 1.0, respectively) when compared with the plain DIT solution (2.72 ± 0.31 μg/cm2/h and 2.3, respectively). Skin separation studies and confocal laser scanning microscope images showed that the dye-loaded dendrimers exhibits deposition of dye in pilosebaceous compartment. These studies demonstrate that PPI can be exploited to improve the topical bioavailability of the molecules in a controlled pattern. The enhanced accumulation of DIT via dendrimer carrier within the skin might help optimize targeting of this drug to the epidermal and dermal sites, thus creating new opportunities for well-controlled, modern topical application of DIT for the treatment of psoriasis.

ChemInform Abstract: Intramolecular Cyclization of γ‐Acetylenic Acids Using Dendrimer‐Encapsulated Pd2+ Catalysts.

AbstractThe polypropylene imine dendrimer (Gx‐TEBA)‐encapsulated Pd catalysts are prepared by complexation of PdCl2 with internal tertiary amino groups and can be applied to induce the intramolecular cyclization of acetylenic acids.

Nanomechanical properties of hydroxyapatite (HAP) with DAB dendrimers (poly-propylene imine) coatings onto titanium surfaces

Abstract Coatings of hydroxyapatite (HAP) nanorods onto titanium surfaces were synthesized with the aim to improve coatings’ mechanical properties and adhesion to the substrate. The coatings are consisting of HAP nanorods synthesized in the presence of a cationic fourth generation diaminobutane poly(propylene imine) dendrimer (DAB) bearing 32 amine end groups employing varying calcium: dendrimer ratios and varying hydrothermal treatments. The quality, surface morphology and structure of the coatings were characterized with X-ray diffraction, thermogravimetric analysis, scanning electron microscopy and energy dispersive microanalysis. Wear resistance and adhesion properties of the coatings onto titanium substrates were studied through nanoindentation analysis. The experimental conditions, namely the calcium: dendrimer molar ratio and the hydrothermal treatment temperature were carefully selected; thus, it was possible to produce coatings of high hardness and elastic modulus values (ranging between 1–4.5 GPa and 40–150 GPa, respectively) and/or high wear resistance and plastic deformation values.

Molecular weight and architectural dependence of well-defined star-shaped poly(lysine) as a gene delivery vector.

A series of well-defined star-shaped polypeptides were successfully synthesised by the ring opening polymerisation (ROP) of the N-carboxyanhydride (NCA) of ε-carbobenzyloxy-l-lysine (ZLL) using a range of generations of polypropylene imine (PPI) dendrimers as multifunctional initiators. The monomer feed ratio and dendrimer generation were varied to afford a series of polypeptide dendrimer hybrids with superior structural versatility and functionality. Subsequent protecting group removal yielded star-shaped poly(lysine) of controlled variation in polypeptide chain length and arm multiplicity. Star-shaped PLL polymers were used to prepare pDNA and siRNA to form "polyplexes" to determine their ability to complex different nucleic acid cargoes and were compared with linear PLL polyplex controls. Significant differences in size and surface charge were seen between star-shaped PLL polyplexes and linear PLL polyplexes for both cargoes. The star-shaped polypeptides were capable of more effective complexation of both nucleic acids at low N/P ratios compared to linear PLL as evidenced by zeta potential and electrophoretic data. This was particularly evident in siRNA polyplexes as linear PLL failed to completely complex siRNA into nanocomplexes of appropriate size for cell transfection i.e. <200 nm in size, while star poly(lysine) formed siRNA polyplexes <100 nm at certain N/P ratios, albeit strongly dependent on the particular molecular weight and architecture, as analysed by dynamic light scattering (DLS). Atomic force microscopy (AFM) identified discrete spherically shaped polyplexes for all star-shaped polypeptide-based polyplexes while linear PLL formed elongated irregular shaped complexes. This difference in morphology may go some way towards explaining the 300-fold increase in luciferase expression seen for star-shaped PLL polyplexes G5(64)-PLL40 compared to linear PLL pGLuc polyplexes in epithelial cells. Each of the PPI-PLL polymers appeared to be capable of protecting the nucleic acid cargoes from degradation by the relevant nuclease enzyme as effectively as the positive control polyethyleneimine (PEI) polyplexes. Overall the promising nucleic acid complexation, sizing, morphology and protection capacity of two different genetic "cargoes" highlight the potential of polypeptide dendrimer hybrids as gene delivery vectors.

Synthesis and characterization of dendritic salicylaldimine complexes of copper and cobalt and their use as catalyst precursors in the aerobic hydroxylation of phenol

A series of generation 1 (G1) and generation 2 (G2) salicylaldimine functionalized polypropylene imine dendrimers were used to prepare a range of new copper and cobalt metallodendrimers. These were found to be efficient catalysts in the aerobic hydroxylation of phenol using H2O2 and molecular oxygen as oxidants. The major products obtained were catechol and hydroquinone. The selectivity to these two products was greatly influenced by the nature of the metallodendrimer as well as by the pH of the reaction medium.

Star polypeptides by NCA polymerisation from dendritic initiators: synthesis and enzyme controlled payload release

Well-defined star polypeptides were successfully synthesised by initiation of γ-benzyl-L-glutamate N-carboxyanhydride (NCA) from polypropylene imine (PPI) dendrimers. The dendrimer generation and the dendrimer to NCA ratio were systematically varied to afford a range of star shaped architectures with a maximum of 8 to 64 poly(γ-benzyl-L-glutamate) (PBLG) arms. High molar masses up to 500 000 g mol−1 were achieved that were otherwise unobtainable for the analogous linear polypeptides in the absence of the dendrimer core. By deprotection the PBLG star polypeptides were converted into poly(L-glutamic acid) (PGA) star polypeptides. Various concentrations of rhodamine B could be loaded into the polypeptide star architectures dependent on the number of PGA arms and the length of the grafted polypeptide chain produced. Furthermore, the polypeptidic nature of PGA-grafted dendrimers ensures their responsiveness, through controlled degradation, to the target enzyme thermolysin. An enzyme-responsive release mechanism was devised and demonstrated in which rhodamine B payload was released upon incubation with thermolysin but not the control enzyme chymotrypsin. The rate and extent of rhodamine B release was dependent on the composition of the hybrid material, which can be readily tuned to provide highly specific temporal and spatial controlled release.

Nanostructured Macromolecular Metal Containing Materials in Catalysis

AbstractSummary: Nanostructured regular materials based on cross‐linked polypropylene imine (PPI) dendrimers and silica‐gel polyamine composites were used as a support for the synthesis of Pd nanoparticles. The materials were tested as catalysts and displayed a high activity and selectivity for the hydrogenation of conjugated double bonds.

Characterization of complexes formed by polypropylene imine dendrimers and anti-HIV oligonucleotides

Current anti-HIV therapies are capable of controlling viral infection but do not represent a definitive cure. They rely on the administration of antiretroviral nucleoside analogues, either alone or in combination with vectors. Dendrimers are branched, synthetic polymers with layered architectures, promising non-viral vectors in gene therapy. The aim of the paper was to study the interactions between three anti-HIV antisense oligonucleotides (ODNs): SREV, ANTI TAR, GEM91 and different generation polypropylene imine dendrimers (PPI) by monitoring changes in the fluorescence polarization of fluorescein attached to the ends of the ODNs when increasing concentrations of dendrimers were added. Laser Doppler electrophoresis, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to characterize, respectively, zeta potential, particle size and morphology of dendriplexes formed in different molar ratios. Antisense oligonucleotides interacted with polypropylene imine dendrimers in different molar ratios depending on generation. Zeta potential of dendriplexes varied from (−25 to −21)mV to −5mV (for PPIG3 and PPIG4 complexes) and to zero (for PPIG2 complexes). The structures presented a polydisperse size from about 50nm to even 700–800nm by TEM and about 250nm by DLS. It means that besides single dendriplexes, aggregates were also present.

Influence of Surface Functionality of Poly(propylene imine) Dendrimers on Protease Resistance and Propagation of the Scrapie Prion Protein

Accumulation of PrP(Sc), an insoluble and protease-resistant pathogenic isoform of the cellular prion protein (PrP(C)), is a hallmark in prion diseases. Branched polyamines, including PPI (poly(propylene imine)) dendrimers, are able to remove protease resistant PrP(Sc) and abolish infectivity, offering possible applications for therapy. These dendrimer types are thought to act through their positively charged amino surface groups. In the present study, the molecular basis of the antiprion activity of dendrimers was further investigated, employing modified PPI dendrimers in which the positively charged amino surface groups were substituted with neutral carbohydrate units of maltose (mPPI) or maltotriose (m3PPI). Modification of surface groups greatly reduced the toxicity associated with unmodified PPI but did not abolish its antiprion activity, suggesting that the presence of cationic surface groups is not essential for dendrimer action. PPI and mPPI dendrimers of generation 5 were equally effective in reducing levels of protease-resistant PrP(Sc) (PrP(res)) in a dose- and time-dependent manner in ScN2a cells and in pre-existing aggregates in homogenates from infected brain. Solubility assays revealed that total levels of PrP(Sc) in scrapie-infected mouse neuroblastoma (ScN2a) cells were reduced by mPPI. Coupled with the known ability of polyamino dendrimers to render protease-resistant PrP(Sc) in pre-existing aggregates of PrP(Sc) susceptible to proteolysis, these findings strongly suggest that within infected cells dendrimers reduce total amounts of PrP(Sc) by mediating its denaturation and subsequent elimination.

Ligand anchored dendrimers based nanoconstructs for effective targeting to cancer cells

Dendrimers are considered versatile carriers especially for the treatment of diseases like cancer, AIDS, malaria etc. Cancer is a worldwide threat particularly in developing countries. A breakthrough research in this regard is a prime requirement. In the present study, folic acid was conjugated to fifth generation polypropylene imine (PPI) dendrimers and characterized through IR, NMR ( 13C and 1H), ESI mass spectroscopy as well as electron microscopic studies. Doxorubicin (DOX), an effective anticancer drug, was used in the present study to develop and explore the anticancer potential of the dendrimer based formulations. DOX was loaded (approximately 26 and 65%) to the PPI dendrimers as well as folate conjugated PPI (PPI–FA) dendrimers, respectively. These ligand conjugated dendrimers displayed very less (approximately 3 and 4%, respectively, for PPI–FA and PPI–FA–DOX) hemolysis. The developed formulation PPI–FA–DOX was stable enough. In vitro drug release of the formulation was found to be faster in the acidic media than at the higher pH. The prepared formulation displayed a higher cell uptake in MCF-7 cancer cell lines as evidenced by fluorescence studies. The results suggested that, in future, folic acid conjugated PPI dendrimers may emerge as a better choice for anticancer drug targeting.

Nanocatalysts based on dendrimers

Nanostructured regular materials based on dendrimers bound by covalent or coordination bonds between surface functional groups were synthesized. Bimetallic Cu(II) and Pd(II) metal complexes with nitrile-based dendrimers demonstrated high activity in Wacker oxidation of terminal alkenes along with good selectivity for methylketone formation. New heterogeneous catalysts based on Pd nanoparticles and cross-linked polypropylene imine (PPI) and polyamidoamine (PAMAM) dendrimers were prepared and examined for selective hydrogenation of unsaturated compounds.

Dextran conjugated dendritic nanoconstructs as potential vectors for anti-cancer agent

The purpose of the present investigation was to evaluate the potential of surface engineered polypropylene imine (PPI) dendrimers as nanoscale drug delivery units for site-specific delivery of a model anti-cancer agent, doxorubicin·hydrochloride (DOX). Dextran conjugated PPI dendrimers were synthesized, characterized and further loaded with DOX. The developed formulation was characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) and transmission electron microscopic (TEM) studies. Dendrimer formulation was evaluated for in vitro drug release and haemolytic studies under various pH conditions. Cell uptake and cytotoxicity studies were performed on A549 cell lines using MTT cell proliferation assay. In vivo studies were conducted for evaluation of various pharmacokinetic parameters and tissue distribution pattern. In vitro, formulation displayed initial rapid release of the drug followed by rather slow release. Further, the dextran conjugated dendrimer formulation was found to be least haemolytic but more cytotoxic as compared to free drug. Cell uptake studies depicted that the formulation was preferably taken up by the tumor cells when compared to free drug. The conjugation of oxidized polyaldehyde dextran imparts macromolecular nature to the dendritic carrier, consequently the formulation was found to selectively enter highly porous mass of tumor cells at the same time precluding normal tissues. Thus it was concluded that the drug loaded dendrimer formulation would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.

Functional Group Density and Recognition in Polymer Nanotubes

Branching out: The use of polypropylene–imine dendrimers as scaffolds leads to the precise control of the pore size of functionalized nanoporous membranes, which can be used for molecular recognition. The nanopores show a finite transition in generation-dependent molecular discrimination capabilities, which arises not only from the size of the final pores, but also from the functional group density of the dendrimers (see picture).

Glycopeptide dendrimers. Part I

Glycopeptide dendrimers are branched structures containing both carbohydrates and peptides. Various classes of these compounds differing in composition and structure are mentioned, together with their practical use spanning from catalysis, transport vehicles to synthetic vaccines. The main stress is given to glycopeptide dendrimers, namely multiple antigen glycopeptides (MAGs). In MAGs, the core, branches or both are composed of amino acids or peptides. Other classes of glycodendrimers (PAMAM, polypropylene imine, cyclodextrin, calixarene, etc.) are mentioned too, but to a smaller extent. Their syntheses, physicochemical properties and biological activities are given with many examples. Glycopeptide dendrimers can be used as inhibitors of cell surface protein-carbohydrate interactions, intervention with bacterial adhesion, for studying of recognition processes, diagnostics, imaging and contrast agents, mimetics, for complexation of different cationts, as site-specific molecular delivery systems, for therapeutic purposes, as immunodiagnostics and in drug design. Biomedical applications of glycopeptide dendrimers as drug and gene delivery systems are also given.

An electrochemical DNA biosensor developed on novel multinuclear nickel(II) salicylaldimine metallodendrimer platform

An electrochemical DNA biosensor (EDB) was prepared using an oligonucleotide of 21 bases with sequence NH 2-5′-GAGGAGTTGGGGGAGCACATT-3′ (probe DNA) immobilized on a novel multinuclear nickel(II) salicylaldimine metallodendrimer on glassy carbon electrode (GCE). The metallodendrimer was synthesized from amino functionalized polypropylene imine dendrimer, DAB-(NH 2) 8. The EDB was prepared by depositing probe DNA on a dendrimer-modified GCE surface and left to immobilize for 1 h. Voltammetric and electrochemical impedance spectroscopic (EIS) studies were carried out to characterize the novel metallodendrimer, the EDB and its hybridization response in PBS using [Fe(CN) 6] 3−/4− as a redox probe at pH 7.2. The metallodendrimer was electroactive in PBS with two reversible redox couples at E°′ = +200 mV and E°′ = +434 mV; catalytic by reducing the E pa of [Fe(CN) 6] 3−/4− by 22 mV; conducting and has diffusion coefficient of 8.597 × 10 −8 cm 2 s −1. From the EIS circuit fitting results, the EDB responded to 5 nM target DNA by exhibiting a decrease in charge transfer resistance ( R ct) in PBS and increase in R ct in [Fe(CN) 6] 3−/4− redox probe; while in voltammetry, increase in peak anodic current was observed in PBS after hybridization, thus giving the EDB a dual probe advantage.

Glycoconjugated peptide dendrimers-based nanoparticulate system for the delivery of chloroquine phosphate

Dendrimers consisting of different molecules of metabolic pathways such as amino acids can greatly reduce the toxicity associated with amine-terminated dendrimers e.g. polyamidoamine (PAMAM) and polypropylene imine (PPI) dendrimers. In the present study, poly- l-lysine dendrimers having polyethyleneglycol (PEG-1000) as core, were synthesized upto fourth generation. Dendrimers were synthesized by alternating protection and deprotection steps of l-lysine by di-BOC (di-tertiary butyl pyrocarbonate) till the formation of 4.0G peptide dendrimer took place. d-galactose was selected as model sugar for peripheral conjugation (coating) of these peptide dendrimer. The complete formation of uncoated and galactose-coated poly- l-lysine dendrimers was characterized by transmission electron microscopy (TEM), IR, NMR and MALDI TOF mass spectroscopic studies. Chloroquine phosphate (CP)-loaded uncoated and coated dendrimers were evaluated for in vitro drug release rate, hemolytic toxicity and stability studies. Ex vivo cellular uptake studies of uncoated and coated drug dendrimer formulations in macrophages revealed almost 5 times reduced phagocytosis due to galactose coating ( p<0.0001). In vitro–in vivo release behavior indicated possibilities of galactose-coated drug dendrimers formulation in controlled drug delivery of CP. Galactose coated formulations drastically reduced hemolytic toxicity compared to uncoated poly- l-lysine formulation as well as plain drug. Hematological data suggests that galactose-coated formulations are less immunogenic compared to uncoated formulations. Finally, it can be concluded that galactose-coated polylysine dendrimers can be utilized for controlled delivery of CP more safely compared to its uncoated formulation both in vitro and in vivo.

Solubilization and Release Properties of Dendrimers. Evaluation as Prospective Drug Delivery Systems

The polarity and accessibility to the interior of several dendrimers using phenanthrene, anthracene and tetrabenzonaphtalene as probe molecules have been investigated. In addition the prospective application of the dendrimers as drug carriers was evaluated by incorporating 5(6)-methylbenzo[1,2-c]1,2,5-oxadiazole N 1-oxide] (1) and 2′-(benzo[1,2-c] 1,2,5-oxadiazol-5(6)-yl(N1-oxide) methylidene]-1-methoxy methane hydrazide (2). These compounds have antichagasic therapeutic activity but very low water solubility, which limits their application. Polypropylene imine dendrimers with amine terminal groups (DAB-16AT and DAB-32AT) and polyamide amine (PAMAM) dendrimers with carboxylate terminal groups (PAMAM-32CT), with amine terminal groups, (PAMAM-8AT and PAMAM-32AT) and with hydroxyl terminal groups (PAMAM-32OHT) were chosen for this study. Approximately one molecule of phenanthrene or anthracene was encapsulated in PAMAM-32CT, PAMAM-32AT, PAMAM-32OHT and DAB-32AT dendrimers. However, slight encapsulation was observed working with PAMAM-8AT and DAB-16AT. The studies with tetrabenzonaphtalene show that the guest molecule might only be partially caged within the dendrimer host. However, for relatively insoluble solutes the efficiency to encapsulate can be dictated by the saturation in the aqueous phase besides the dendrimer capacity to dissolve it. These dendrimers are also able to encapsulate and consequently solubilize 1 and 2 oxadiazol. However, PAMAM dendrimers are better for encapsulation and retention due to guest-host specific interactions. These interactions can be diminished by lowering the pH to allow a controlled deliverance of the drug.

New Liquid Phases for the Gas Chromatographic Separation of Strong Bases on Capillary Columns

The current practice of pretreating the solid support with free alkali to increase separation efficiency for basic compounds proved to be unsuitable for capillary columns. Instead of this, homogenous organic materials of high base strength are required. We found polyethylene imine (PEI) and polypropylene imine (PPI) to be very efficient as liquid phases of capillary columns for the separation of bases. The preparation of polymers is mentioned. Silanization or acetylation of the free hydroxyl groups of carbowax-type substrate makes them more suitable for use as liquid phases in capillary columns