Polyethylenimine (PEI) is one of the most broadly used polycations for gene delivery due to its high transfection efficiency and commercial availability but materials are cytotoxic and often polydisperse. The goal of current work is to develop an alternative family of polycations based on controlled living radical polymerization (CLRP) and to optimize the polymer structure for efficient gene delivery. In this study, well-defined poly(glycidyl methacrylate)(P(GMA)) homopolymers were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization followed by decoration using three different types of oligoamines, i.e., tetraethylenepentamine (TEPA), pentaethylenehexamine (PEHA), and tris(2-aminoethyl)amine (TREN), respectively, to generate various P(GMA-oligoamine) homopolycations. The effect of P(GMA) backbone length and structure of oligoamine on gene transfer efficiency was then determined. The optimal polymer, P(GMA-TEPA)(50), provided comparable transfection efficiency but lower cytotoxicity than PEI. P(GMA-TEPA)(50) was then used as the cationic block in diblock copolymers containing hydrophilic N-(2-hydroxypropyl) methacrylamide (HPMA) and oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA). Polyplexes of block copolymers were stable against aggregation in physiological salt condition and in Opti-MEM due to the shielding effect of P(HPMA) and P(OEGMA). However, the presence of the HPMA/OEGMA block significantly decreased the transfection efficacy of P(GMA-TEPA)(50) homopolycation. To compensate for reduced cell uptake caused by the hydrophilic shell of polyplex, the integrin-binding peptide, RGD, was conjugated to the hydrophilic chain end of P(OEGMA)(15)-b-P(GMA-TEPA)(50) copolymer by Michael-type addition reaction. At low polymer to DNA ratios, the RGD-functionalized polymer showed increased gene delivery efficiency to HeLa cells compared to analogous polymers lacking RGD.
Magnetic paper were prepared via the in situ synthesis method with ferrites in the presence of polyethylenimine (PEI). In this work, the thermomechanical pulp (TMP) fibers were used due to low percentage of collapse lumen and the large lumen size for optimum loading degree. Four cycles of the reaction were performed on the TMP fibers with pH values of 4-10. It was found that variation of pH value played an important role in the loading degree of pulp during synthesis process. The magnetic, morphological and structural properties of the magnetic paper obtained were reported. At the
optimum pH of 6.0, saturation magnetization was found to be 3.08 emu/g, remainance magnetization was 0.11 emu/g and coercive force was 12.64 Oe. The optimum loading degree was found to be 23.25%.
Precipitated calcium carbonate fillers were loaded into the lumen of bleached mixed tropical hardwood pulp using polyethylenimine (PEI) and alum. Our results indicated that the addition of (PEI) increased the degree of loading of precipitated calcium carbonate (PCC) into the lumen of fibers. The degree of loading also increased with the addition of alum together with PEI. The mechanical strengths of the produced lumen loaded paper increased with the addition of PEI and alum. Meanwhile the mechanical strength without alum had slightly increased the mechanical strengths of the paper. Electron micrographs revealed that the PCC fillers were successfully loaded into the lumen of the fibers.
Covalently cross-linked nanogels were prepared via irradiation of inverse micelles that had been preparedfrom radiation crosslinkable polymer, water, oil and surfactant. A mixture of polymer, water, heptane andsodium dioctyl sulfosuccinate (AOT) at certain compositions forms inverse micelles with the size rangingfrom 2 to 8 nm. The hydrophilic head of the surfactant facilitates encapsulation of water soluble polymer.If the entrapped polymer is radiation crosslinkable, it is expected that upon irradiation, polymerizationshall take place in such small and confined space, leading to formation of nano-sized polymeric gel.Meanwhile, emulsion at 2 nm size was chosen for gamma irradiation process. The formation of thenano-sized discreet gel using irradiation of inverse micelles technique was proven at a dose as low as 5kGy to obtain nanogel sized ~ 95 nm.
Reverse genetics has been used to generate recombinant Newcastle disease virus with enhanced immunogenic properties for vaccine development. The system, which involves co-transfecting the viral antigenomic plasmid with three helper plasmids into a T7 RNA polymerase-expressing cell to produce viral progenies, poses a great challenge. We have modified the standard transfection method to improve the transfection efficiency of the plasmids, resulting in a higher titer of virus progeny production. Two transfection reagents (i.e., lipofectamine and polyethylenimine) were used to compare the transfection efficiency of the four plasmids. The virus progenies produced were quantitated with flow cytometry analysis of the infectious virus unit. The modified transfection method increased the titer of virus progenies compared with that of the standard transfection method.
Removal of Cr(VI) ions from aqueous solution was investigated using modified palm shell activated carbon. Low Molecular Weight Polyethyleneimine (LMW PEI) was used for impregnation purpose. The maximum amount of LMW PEI adsorbed on activated carbon was determined to be approximately 228.2mg/g carbon. The adsorption experiments were carried out in a batch system using potassium dichromate K(2)Cr(2)O(7) as the source of Cr(VI) in the synthetic waste water and modified palm shell activated carbon as the adsorbent. The effects of pH, concentration of Cr(VI) and PEI loaded on activated carbon were studied. The adsorption data were found to fit well with the Freundlich isotherm model. This modified Palm shell activated carbon showed high adsorption capacity for chromium ions.
The effects of polyethyleneimine (PEI) impregnation on the Pb(2+) adsorption kinetics of palm shell-activated carbon and pH profile of bulk solution were investigated. Adsorption data were fitted to four established adsorption kinetics models, namely, pseudo-first-order, pseudo-second-order, Elovich equation and intraparticle diffusion. It was found that PEI impregnation at 16.68 and 29.82 wt% PEI/AC increased the Pb(2+) uptake rate while the opposite was observed for PEI impregnation at 4.76 and 8.41 wt% PEI/AC. The increased uptake rates were due to higher concentration of PEI molecules on the surface of clogged pores as well as varying pore volumes. The adsorption kinetics data fitted the pseudo-second-order model better than the pseudo-first-order model, implying chemisorption was the rate-controlling step. The bulk solution pH generally showed an increasing trend from the use of virgin to PEI-impregnated activated carbon.
This study deals with the removal of chromium species from aqueous dilute solutions using polymer-enhanced ultrafiltration (PEUF) process. Three water soluble polymers, namely chitosan, polyethyleneimine (PEI) and pectin were selected for this study. The ultrafiltration studies were carried out using a laboratory scale ultrafiltration system equipped with 500,000 MWCO polysulfone hollow fiber membrane. The effects of pH and polymer composition on rejection coefficient and permeate flux at constant pressure have been investigated. For Cr(III), high rejections approaching 100% were obtained at pH higher than 7 for the three tested polymers. With chitosan and pectin, Cr(VI) retention showed a slight increase with solution pH and did not exceed a value of 50%. An interesting result was obtained with PEI. The retention of Cr(VI) approached 100% at low pH and decreased when the pH was increased. This behavior is opposite to what one can expect in the polymer-enhanced ultrafiltration of heavy metals. Furthermore, the concentration of polymer was found to have little effect on rejection. Permeate flux remained almost constant around 25% of pure water flux.
Aminoacylase I (E.C.3.5.1.14) was immobilized by entrapment in calcium alginate beads coated with polyethyleneimine for the production of L-phenylalanine by the hydrolysis of a racemic mixture of N-acetyl-DL-phenylalanine. The operational stability in terms of batch operation and continuous reaction in packed-bed bioreactor were studied. Kinetic constants, Km and Vmax values of free and immobilized enzymes were studied. Polyethyleneimine treatment was found to enhance the operational stability of the enzyme though its activity was substantially reduced. When polyethyleneimine-coated calcium alginate beads were packed into packed bed bioreactor, it was stable for at least 25 days under continuous operation without appreciable loss of activity.
Chitosan-polyethyleneimine with calcium chloride as ionic cross-linker (CsPC) was synthesized as a new kind of adsorbent using a simple, green and cost-effective technique. The adsorption properties of the adsorbent for Acid Red 88 (AR88) dye, as a model analyte, were investigated in a batch system as the function of solution pH (pH 3-12), initial AR88 concentration (50-500 mg L-1), contact time (0-24 h), and temperature (30-50 °C). Results showed that the adsorption process obeyed the pseudo-first order kinetic model and the adsorption rate was governed by both intra-particle and liquid-film mechanism. Equilibrium data were well correlated with the Freundlich isotherm model, with the calculated maximum adsorption capacity (qm) of 1000 mg g-1 at 30 °C. The findings underlined CsPC to be an effective and efficient adsorbent, which can be easily synthesized via one-step process with promising prospects for the removal of AR88 or any other similar dyes from the aqueous solutions.
Efficient delivery of adequate active ingredients to targeted malignant cells is critical, attributing to recurrent biophysical and biochemical challenges associated with conventional pharmaceutical delivery systems. These challenges include drug leakage, low targeting capability, high systemic cytotoxicity, and poor pharmacokinetics and pharmacodynamics. Targeted delivery system is a promising development to deliver sufficient amounts of drug molecules to target cells in a controlled release pattern mode. Aptameric ligands possess unique affinity targeting capabilities which can be exploited in the design of high pay-load drug formulations to navigate active molecules to the malignant sites. This study focuses on the development of a copolymeric and multifunctional drug-loaded aptamer-conjugated poly(lactide-co-glycolic acid)-polyethylenimine (PLGA-PEI) (DPAP) delivery system, via a layer-by-layer synthesis method, using a water-in-oil-in-water double emulsion approach. The binding characteristics, targeting capability, biophysical properties, encapsulation efficiency, and drug release profile of the DPAP system were investigated under varying conditions of ionic strength, polymer composition and molecular weight (MW), and degree of PEGylation of the synthetic core. Experimental results showed increased drug release rate with increasing buffer ionic strength. DPAP particulate system obtained the highest drug release of 50% at day 9 at 1 M NaCl ionic strength. DPAP formulation, using PLGA 65:35 and PEI MW of ∼800 Da, demonstrated an encapsulation efficiency of 78.93%, and a loading capacity of 0.1605 mg bovine serum albumin per mg PLGA. DPAP (PLGA 65:35, PEI MW∼25 kDa) formulation showed a high release rate with a biphasic release profile. Experimental data depicted a lower targeting power and reduced drug release rate for the PEGylated DPAP formulations. The outcomes from the present study lay the foundation to optimize the performance of DPAP system as an effective synthetic drug carrier for targeted delivery.
Recent advances and applications of biomolecule-responsive hydrogels, namely, glucose-responsive hydrogels, protein-responsive hydrogels, and nucleic-acid-responsive hydrogels are highlighted. However, achieving the ultimate purpose of using biomolecule-responsive hydrogels in preclinical and clinical areas is still at the very early stage and calls for more novel designing concepts and advance ideas. On the way toward the real/clinical application of biomolecule-responsive hydrogels, plenty of factors should be extensively studied and examined under both in vitro and in vivo conditions. For example, biocompatibility, biointegration, and toxicity of biomolecule-responsive hydrogels should be carefully evaluated. From the living body's point of view, biocompatibility is seriously depended on the interactions at the tissue/polymer interface. These interactions are influenced by physical nature, chemical structure, surface properties, and degradation of the materials. In addition, the developments of advanced hydrogels with tunable biological and mechanical properties which cause no/low side effects are of great importance.
We present an all-atom molecular dynamics study of the effect of a range of organic solvents (dichloromethane, diethyl ether, toluene, methanol, dimethyl sulfoxide, and tetrahydrofuran) on the conformations of a nanogel star polymeric nanoparticle with solvophobic and solvophilic structural elements. These nanoparticles are of particular interest for drug delivery applications. As drug loading generally takes place in an organic solvent, this work serves to provide insight into the factors controlling the early steps of that process. Our work suggests that nanoparticle conformational structure is highly sensitive to the choice of solvent, providing avenues for further study as well as predictions for both computational and experimental explorations of the drug-loading process. Our findings suggest that when used in the drug-loading process, dichloromethane, tetrahydrofuran, and toluene allow for a more extensive and increased drug-loading into the interior of nanogel star polymers of the composition studied here. In contrast, methanol is more likely to support shallow or surface loading and, consequently, faster drug release rates. Finally, diethyl ether should not work in a formulation process since none of the regions of the nanogel star polymer appear to be sufficiently solvated by it.
Organo-metal halide perovskite field-effect transistors present serious challenges in terms of device stability and hysteresis in the current-voltage characteristics. Migration of ions located at grain boundaries and surface defects in the perovskite film are the main reasons for instability and hysteresis issues. Here, we introduce a perovskite grain molecular cross-linking approach combined with amine-based surface passivation to address these issues. Molecular cross-linking was achieved through hydrogen bond interactions between perovskite halogens and dangling bonds present at grain boundaries and a hydrophobic cross-linker, namely diethyl-(12-phosphonododecyl)phosphonate, added to the precursor solution. With our approach, we obtained smooth and compact perovskite layers composed of tightly bound grains hence significantly suppressing the generation and migration of ions. Moreover, we achieved efficient surface passivation of the perovskite films upon surface treatment with an amine-bearing polymer, namely polyethylenimine ethoxylated. With our synergistic grain and surface passivation approach, we were able to demonstrate the first perovskite transistor with a complete lack of hysteresis and unprecedented stability upon continuous operation under ambient conditions. Added to the merits are its ambipolar transport of opposite carriers with balanced hole and electron mobilities of 4.02 and 3.35 cm2 V-1 s-1, respectively, its high Ion/Ioff ratio >104 and the lowest sub-threshold swing of 267 mV dec-1 reported to date for any perovskite transistor. These remarkable achievements obtained through a cost-effective molecular cross-linking of grains combined with amine-based surface passivation of the perovskite films open a new era and pave the way for the practical application of perovskite transistors in low-cost electronic circuits.
Overuse of antibiotics has led to the development of multi drug resistant strains. Antibiotic resistance is a major drawback in the biomedical field since medical implants are prone to infection by biofilms of antibiotic resistant strains of bacteria. With increasing prevalence of antibiotic resistant pathogenic bacteria, the search for alternative method is utmost importance. In this regard, magnetic nanoparticles are commonly used as a substitute for antibiotics that can circumvent the problem of biofilms growth on the surface of biomedical implants. Iron oxide nanoparticles (IONPs) have unique magnetic properties that can be exploited in various ways in the biomedical applications. IONPs are engineered employing different methods to induce surface functionalization that include the use of polyethyleneimine and oleic acid. IONPs have a mechanical effect on biofilms when in presence of an external magnet. In this review, a detailed description of surface engineered magnetic nanoparticles as ideal antibacterial agents is provided, accompanied by various methods of literature review. This article is protected by copyright. All rights reserved.
Many diseases are potential targets for gene therapy using either non-viral or viral vectors. Unlike nonviralmethods, viral vectors, such as lentiviruses, have the ability to integrate into the host chromosome,which can lead to long-term transgene expression. Lentiviruses have advantages over other types ofviruses due to their capacity to transduce non-dividing cells. An optimized generation of lentivirusescarrying green fluorescent protein (GFP) reporter gene driven by either UbC (LV/UbC/GFP) orCMV (LV/CMV/GFP) promoter is described in this paper. The lentiviruses were produced by cotransfectinglentiviral expression constructs and packaging mix into 293FT lentivirus producer cell lines.Lipofectamine was highly efficient in transfecting the cells compared to Transfast and Polyethyleneimine(PEI). Following cell transfection, syncytia were clearly visible at day 2. Lentiviruses were harvestedat days 1, 2 and 3 post-transfection. The highest transduction efficiency was read from LV/CMV/GFPharvested at day 2 post-transfection and LV/UbC/GFP harvested at day 3 post-transfection. Finally,the GFP expression in COS-7 cells was determined at day 2 and day 14 post-transduction for transientand stable GFP expression. It was found that the GFP expression declined overtime. However, thetransduction efficiency and duration of the transgene expression in COS-7 cells transduced with LV/CMV/GFP were higher compared to LV/UbC/GFP. In conclusion, we have successfully produced lentivirusescarrying GFP with different promoters and shown that the viruses were able to infect COS-7 cells atdifferent efficiencies. Meanwhile, the generation of the active lentiviruses will allow us to proceed to the subsequent analysis of the effect of regulatory elements in future study.
Haruan or Channa striatus is source of protein that is widely consumed in the region and its extract
is well known for having medical values. It is of great advantage if this product could be taken
orally rather than by injection because the oral route of drug delivery is still preferred by the vast
majority of patients. However protein and peptides can be denatured or degraded by the acidic pH
of the stomach and the presence of endogenous enzymes. In order to protect or prevent digestion
and degradation of the protein in the stomach and to ensure the protein reaches the gastro
intestinal (GI) tract, Carboxymethyl Starch (CMS) nanogel system was developed using electron
irradiation method. However stability of HTE during the irradiation process needed to be studied
before being developed further. In this study, the HTE was irradiated using electron beams. Its
stability was analysed in terms of physical and chemical changes by looking at colour difference,
melting point by using Differential Scanning Calorimetry (DSC) and molecular bonds by using
Fourier Transform Infrared (FTIR) respectively. The results of this study were that no apparent
colour difference was observed with HTE before and after irradiation. These observations were
supported by the FTIR and DSC results that showed that there were no changes in molecular bonds
and melting point, compared between no irradiation and irradiation HTE during electron
irradiation up to 10 kGy. Statistically the test showed no significant difference at p < 0.005 between
melting temperatures.
Commercial low-density polyethylene (LDPE) films were UV/ozone treated and coated using a layer-by-layer (LbL) technique by alternating the deposition of polyethyleneimine (PEI) and poly(acrylic acid) (PAA) polymer solutions and antimicrobial silver (Ag). The effects of the initial pH of the PEI/PAA polymer solutions alternating layers (pH 10.5/4 or 9/6.5) on the antimicrobial activity of the developed LbL coatings combined with Ag against Gram-negative and Gram-positive bacteria were investigated. The results from fourier transform infrared spectroscopy and toluidine blue O assay showed that LDPE LbL coated using PEI/PAA polymer solutions with initial pH of 10.5/4 significantly increased the presence of carboxylic acid groups and after Ag attachment the coating had higher antimicrobial activity against both Gram-negative and Gram-positive bacteria compared to the LDPE LbL coated using PEI/PAA polymer solutions with initial pH of 9/6.5. The LDPE LbL coated films using non-modified pH PEI/PAA polymer solutions decreased the water contact-angle indicating an increased hydrophilicity of the film, also increased the tensile strength and roughness of LDPE LbL coated films compared to uncoated LbL samples. The LDPE LbL coated films attached with Ag(+) were UV/ozone treated for 20 min to oxidise Ag(+) to Ag(0). The presence of Ag(0) (Ag nanoparticles (NPs)) on the LDPE LbL coated films was confirmed by XRD, UV-vis spectrophotometer and colour changes. The overall results demonstrated that the LbL technique has the potential to be used as a coating method containing antimicrobial Ag NPs and that the manufactured films could potentially be applied as antimicrobial packaging.
Doxorubicin-loaded micelles were prepared from a copolymer comprising cholic acid (CA) and polyethyleneimine (PEI) for the delivery of antitumor drugs. The CA-PEI copolymer was synthesized via pairing mediated by N,N'-dicyclohexylcarbodiimide and N-hydroxysuccinimide using dichloromethane as a solvent. Fourier transform infrared and nuclear magnetic resonance analyses were performed to verify the formation of an amide linkage between CA and PEI and doxorubicin localization into the copolymer. Dynamic light scattering and transmission electron microscopy studies revealed that the copolymer could self-assemble into micelles with a spherical morphology and an average diameter of <200 nm. The CA-PEI copolymer was also characterized by X-ray diffraction and differential scanning calorimetry. Doxorubicin-loaded micelles were prepared by dialysis method. A drug release study showed reduced drug release with escalating drug content. In a cytotoxicity assay using human colorectal adenocarcinoma (DLD-1) cells, the doxorubicin-loaded CA-PEI micelles exhibited better antitumor activity than that shown by doxorubicin. This is the first study on CA-PEI micelles as doxorubicin carriers, and this study demonstrated that they are promising candidates as carriers for sustained targeted antitumor drug delivery system.
Introduction: Insulin is given by injection, because when administered orally, it would be destroyed by enzymes in the digestive system, hence only about 0.1% reaches blood circulation. The purpose of the present study was to use pH sensitive polyelectrolyte methyl methacrylate (MMA)/itaconic acid (IA) nanogels as carriers in an attempt to improve absorption of insulin administered orally. Methods: Insulin (Ins) was incorporated into the MMA/IA nanogels (NGs) using the polyelectrolyte complexation (PEC) method to form Ins/NGs-PEC. Several parameters, including Ins:NGs ratio, pH, incubation time and stirring rate were optimized during preparation of InsNGs-PEC. The prepared formulations were characterized in terms of particle size (PS), polydispersity index (PdI), zeta potential (ZP) and percent entrapment efficiency (% EE). Results: The optimized InF12 nanogels had a PS, PdI, ZP and %EE of 190.43 nm, 0.186, -16.70 mV and 85.20%, respectively. The InF12 nanogels were lyophilized in the presence of different concentrations of trehalose as cryoprotectant. The lyophilized InF12 containing 2%w/v trahalose (InF12-Tre2 nanogels) was chosen as final formulation which had a PS, PdI, ZP and %EE of 430.50 nm, 0.588, -16.50 mv and 82.10, respectively. The in vitro release of insulin from InF12-Tre2 nanogels in the SGF and SIF were 28.71% and 96.53%, respectively. The stability study conducted at 5±3°C for 3 months showed that lnF12-Tre2 nanogels were stable. The SDS-PAGE assay indicated that the primary structure of insulin in the lnF12-Tre2 nanogels was intact. The in-vivo study in the diabetic rats following oral administration of InF12-Tre2 nanogels at a dose of 100 IU/kg body weight reduced blood glucose level significantly to 51.10% after 6 hours compared to the control groups. Conclusions: The pH sensitive MMA/IA nanogels are potential carriers for oral delivery of insulin as they enhanced the absorption of the drug.