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Four leather substrates from different animals were treated by dispersions containing hydrophilic composite silica-hyperbranched poly(ethylene imine) xerogels. Antimicrobial activity was introduced by incorporating silver nanoparticles and/or benzalkonium chloride. The gel precursor solutions were also infused before gelation to titanium oxide powders typically employed for induction of self-cleaning properties. The dispersions from these biomimetically premade xerogels integrate environmentally friendly materials with short coating times. Scanning electron microscopy (SEM) provided information on the powder distribution onto the leathers. Substrate and coating composition were estimated by infrared spectroscopy (IR) and energy-dispersive X-ray spectroscopy (EDS). Surface hydrophilicity and water permeability were assessed by water-contact angle experiments. The diffusion of the leather's initial components and xerogel additives into the water were measured by Ultraviolet-Visible (UV-Vis) spectroscopy. Protection against GRAM- bacteria was tested for Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae against GRAM+ bacteria for Staphylococcus aureus and Enterococcus faecalis and against fungi for Candida albicans. Antibiofilm capacity experiments were performed against Staphylococcus aureus, Klebsiella pneumoniae, Enterococcus faecalis, and Candida albicans. The application of xerogel dispersions proved an adequate and economically feasible alternative to the direct gel formation into the substrate's pores for the preparation of leathers intended for medical uses.

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In this work, polyethyleneimine (PEI)-grafted chitosan (Chi-g-PEI) was prepared for the fabrication of layer-by-layer (LBL) films for use in sustained-drug-delivery applications. Chi-g-PEI and polyacrylic acid (PAA) multilayer films were formed using the LBL technique. Methylene blue (MB) was used as a model drug for the investigation of loading and release capabilities of the LBL films. Characterizations of the synthesized copolymer were performed using Fourier-transform infrared spectroscopy (FTIR), Nuclear magnetic resonance spectroscopy (NMR), Thermogravimetric analysis (TGA), and X-ray Powder Diffraction (XRD) techniques, and the thickness of the LBL films was measured using Atomic force microscopy (AFM). The drug-loading and -release behaviors of the LBL films were assessed using a UV-visible spectrophotometer. The results showed that the loading capacity and release rate of MB were affected by ionic strength and pH. In addition, it was demonstrated that PEI-grafted chitosan is a good candidate for the assembling of LBL films for drug-delivery applications.

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Cationic polymers endowed with a flexible system for condensing DNA, are regarded as effective materials for gene delivery. The synthesis of poly(ß-amino esters) (pBAEs) based on 1,4-butanediol diacrylate-ethanolamine monomer (1.2:1 molar ratio) and 1,4-butanediol diacrylate-ethylene diamine (1:2 molar ratio) was carried out and modification with 1800 Da polyethyleneimine (PEI) at different weight ratios (3 and 1) as well as conjugation with pullulan in various weight ratios of (0.0625, 0.125, 0.25, and 1) was performed. Gel-retardation assay demonstrated that the synthesized polymers were able to condense DNA at low carrier/plasmid (C/P) ratios. The polyplexes with ratio 3 of PEI (pß1/PEI3) were restricted in all C/P ratios and the polyplexes of pß1/PEI3/pull0.125 were condensed at C/P ratios higher than 0.5. The particle size at C/P was approximately about 200 nm with a positive surface charge. The presence of the pullulan in the structure of the synthesized pBAEs could be effective in reducing toxicity of the base polymer. Highest metabolic activity was dedicated to C/P2 of pß2/PEI3/pull0.125 with 80.6% viability. Furthermore, the most efficient gene reporter delivery was seen at C/P ratio of 6 in pß2/PEI3/pull0.125 nanoparticles. Therefore, pullulan grafting could enhance the cellular response of cells in terms of cytotoxicity and transfection efficiency.

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In hemodialysis process, membrane serves as a barrier between blood and the dialysate. The barrier when contacted by blood accompanied activation of coagulation, immunity, and cellular passageways. In the recent years, hemodialysis membrane's biocompatibility has become a issue which leads to reduce the performance during the separation process. In previous work, we developed and evaluated a cellulose-based membrane blended with polyaziridine or polyetyleneimine in formic acid for hydrophilicity, pure water flux, surface morphology, and permeation efficiency. Biocompatibility was accessed, by conducting cellular viability and cellular attachments tests. In this study, the membrane compared to a non-treated control, and cell viability revealed active and growing cell cultures after 14 days. During the cellular attachment experiment, cell cultures attached to the fabricated membrane simulated the formation of cell junctions, proving that the membrane is non-toxic and biocompatible. CA + PEI + FA membrane tested with a blood mimic fluid having density identical to renal patient's blood. The BSA concentration in the feed solution was the same as that in the blood of the renal patient. The results revealed that the CA + PEI + FA membrane was able to reject 99% bovine serum albumin (BSA) and 69.6% urea. Therefore, from biocompatibility and blood mimic fluid testing, it is confirmed that the CA + PEI + FA membrane is the finest implant for dialysis applications.

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The main objective of this study was to investigate polyethylene imine (PEI) based stereocomplexed nanomiceles for intracellular delivery of rifampicin against Mycobacterium bovis (M. bovis) and their in vitro-in vivo evaluation. The formation of Rifampicin (Rif) loaded isotactic (PEI-g-PLLA and PEI-g-PDLA) and stereocomplexed nanomicelles (StM) of PEI conjugated poly l- and poly d-lactic acid via self-assembly was thoroughly explored. Synthesis of polymer graft was confirmed via FTIR and NMR. A 2-fold reduction in CMC of StM was observed along with decreased particle size in comparison to isotactic nanomicelles. In vitro, StM exhibited a higher encapsulation efficiency and 84 % of drug release in 48 h. at pH 5 with minimal initial burst release in comparison to isotactic nanomicelles. Minimum inhibitory concentration (MIC) of StM was found to be four folds lower in contrast to isotactic nanomicelles. Ex vivo studies exhibited a better uptake of StM and minimum cytotoxicity in murine alveolar macrophages. Following oral administration in mice, drug loaded StM exhibited highest distribution in macrophage rich organs, longer half-life, AUC, AUMC and MRT in comparison to isotactic nanomicelles indicating maximum bioavailability and efficacy of StM. In vivo antimycobacterial activity also demonstrated a higher reduction (2.38fold) in M. bovis CFU at reduced dosing frequency by drug loaded StM in comparison to control group. Thus, StM can be regarded as a simple, stable, efficient, and biocompatible carrier system for delivery of rifampicin to intracellular M. bovis with added advantage of reduced dosing frequency and improved patient compliance.

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Silicon nanowires (SiNWs) are attractive functional nanomaterials for biomedical applications. The ability to easily tune their size and density, potential biocompatibility, and knowledge of the chemical activation of SiNWs surface make them natural tools to interact with biological materials. We evaluated the possibility of exploiting SiNWs as carriers to introduce organic compounds into cells. The cellular toxicity and the internalization capacity of free-standing and label-free SiNWs were tested on Buffalo Green Monkey cells (BGM). Confocal fluorescent observation of SiNWs conjugated with fluorescein-polyethylene imine (PEI) confirmed the internalization of the NWs into the Buffalo Green Monkey Cells (BGM).

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In past decades, alginate-based multilayer microcapsules have been given important attention in various pharmaceutical investigations. Alginate-poly l lysine-alginate (APA) is studied the most. Due to the similarity between the structure of polyethyleneimine (PEI) and poly-L-lysine (PLL) and also lower price of PEI than PLL, this study was conducted to compare the efficacy of linear (LPEI) and branch (BPEI) forms of PEI with PLL as covering layers in fabrication of microcapsules. The microcapsules were fabricated using electrostatic bead generator and their shape/size, surface roughness, mechanical strength, and interlayer interactions were also investigated using optical microscopy, AFM, explosion test and FTIR, respectively. Furthermore, cytotoxicity was evaluated by comparing the two anionic final covering layers alginate (Alg) and sodium cellulose sulphate (NCS) using MTT test. BPEI was excluded from the rest of the study due to its less capacity to strengthen the microcapsules and also the aggregation of the resultant alginate-BPEI-alginate microcapsules, while LPEI showed properties similar to PLL. MTT test also showed that NCS has no superiority over Alg as final covering layer. Therefore, it is concluded that, LPEI could be considered as a more cost effective alternative to PLL and a promising subject for future studies.

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Aim: To encapsulate amphotericin B (AmB) with reduced toxicity and comparable activity. Results & methodology: The α-linolenic acid (ALA)-modified monomethoxy polyethylene glycol-g-PEI-g-ALA conjugate was employed to prepare AmB-loaded micelles (AmB-M). In vitro activity and release behavior of AmB-M were investigated. AmB-M enhanced AmB's water-solubility to 1.2 mg/ml, showing good storage stability. AmB-M could achieve a sustained and slow release of AmB, low hemolysis activity and negligible kidney toxicity when compared with commercial AmB injection. Antifungal activity and biofilm inhibition experiments confirmed that the antifungal activity of AmB-M against Candida albicans was similar to that of AmB injection. Conclusion: Monomethoxy polyethylene glycol-g-PEI-g-ALA micelles could be a preferable choice to treat systemic fungal infections as an efficient drug delivery system.

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We investigated the possibility of improving the performance of polysulfone (PSf) membranes to be used in carbon dioxide capture devices by blending PSf with a commercial polyethylene imine, Lupasol G20, previously modified with benzoyl chloride (mG20). Additive amount ranged between 2 and 20 wt %. Membranes based on these blends were prepared by phase inversion precipitation and exhibited different morphologies with respect to neat PSf. Surface roughness, water contact angles, and water uptake increased with mG20 content. Mass transfer coefficient was also increased for both N2 and CO2; however, this effect was more evident for carbon dioxide. Carbon dioxide absorption performance of composite membranes was evaluated for potassium hydroxide solution in a flat sheet membrane contactor (FSMC) in cross flow module at different liquid flow rates. We found that, at the lowest flow rate, membranes exhibit a very similar behaviour to neat PSf; nevertheless, significant differences can be found at higher flow rates. In particular, the membranes with 2 and 5 wt % additive behave more efficiently than neat PSf. In contrast, 10 and 20 wt % additive content has an adverse effect on CO2 capture when compared with neat PSf. In the former case, a combination of additive chemical affinity to CO2 and membrane porosity can be claimed; in the latter case, the remarkably higher wettability and water uptake could determine membrane clogging and consequent loss of efficiency in the capture device.

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The aim of the present study was to develop zeta potential-changing polyphosphate nanoparticles (pp-NPs) in order to overcome the diffusion barrier of the mucus gel layer and to provide an enhanced cellular uptake. pp-NPs were obtained by in situ gelation between cationic polyethylene imine and anionic polyphosphate. The resulting pp-NPs were characterized with regard to size and zeta potential. Phosphate release studies were carried out by incubation of pp-NPs with isolated as well as cell-associated intestinal alkaline phosphatase (IAP) and quantified by malachite green assay. Correspondingly, change in the zeta potential was measured, and pp-NPs were analyzed by scanning electron microscopy studies. Mucus permeation studies were performed with porcine intestinal mucus via the transwell insert method and rotating tube method. Furthermore, cell viability and cellular uptake were investigated on Caco-2 cells. The resulting pp-NPs displayed a mean size of 269.16 ± 1.12 nm and a zeta potential between -9 and -10 mV in the characterization studies. Within 4 h, a remarkable amount of phosphate was released from pp-NPs incubated with isolated IAP as well as cell-associated IAP and zeta potential raised up from -9.14 ± 0.45 to -1.75 ± 0.46 mV. Compared with dephosphorylated polyphosphate nanoparticles (de-pp-NPs), a significantly enhanced mucus permeation of pp-NPs was observed. Moreover, pp-NPs did not exhibit cytotoxicity. Cellular uptake increased 2.6-fold by conversion of pp-NPs to de-pp-NPs following enzymatic cleavage. Taking the comparatively simple preparation method and the high mucus-permeating properties of pp-NPs and high cellular uptake properties of de-pp-NPs into account, these nanocarriers might be promising novel tools for mucosal drug delivery.

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Since its first harnessing in gene editing in 2012 and successful application in mammalian gene editing in 2013, the CRISPR-Cas9 system exerted magnificent power in all gene-editing-related applications, indicating a sharp thrive of this novel technology. However, there are still some critical drawbacks of the CRISPR-Cas9 system that hampered its broad application in gene editing. Efficient delivery of the Cas9 protein and its partner small guide RNA (sgRNA) to the target cells or tissue is one of the technical bottlenecks. CRISPR-Cas9 delivery via DNA plasmids still plays the big role in gene editing methods. With regard to the disadvantages of CRISPR-Cas9 plasmids, the most acute barrier lies in its large size (>10 kb) and the subsequent low transfection efficiency by conventional transfection method. In this chapter, what we present is an easy method by fabricating CRISPR-Cas9 plasmids into nanoparticle system and efficiently delivered into target cells to achieve gene editing.

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Anticancer immunotherapy is emerging as a promising tumor treatment that can replace the conventional tumor treatment such as surgery, radiation and chemo drug, but its therapeutic effect against solid tumor is limited due to the tumor microenvironment (TME). Herein, to overcome this limitation, the biocompatibility controllable immuno-sensitizer (BCI) based on polyethylene imine that can be applied to solid tumors is developed. BCI accumulates in the tumors by EPR effect and induces in situ tumor destruction that convert tumors into antigen source by biocompatibility change through surface charge switching in response to the acidic TME. Generated tumor antigens promote the maturation of dendritic cells and recruitment of cytotoxic T cells in tumors. Results from in vitro and in vivo experiments reveal that the BCI effectively induces tumor destruction and antitumor immune response. In consequence, the synergic effect of in situ tumor destruction and antitumor immune response induced by BCI's biocompatibility conversion remarkably enhances immunotherapeutic effect. This study may provide a way to improve immunotherapeutic effect on solid tumors by demonstrating the therapeutic effect of BCI against solid tumor and suggest a platform to control the toxicity of cationic polymer for the its extended biomedical application.

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An adsorbent hydrochar was synthesized from corn cobs and modified with polyethylene imine (PEI). The hydrochars before and after modification were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis. FTIR and XPS revealed that the PEI was grafted onto the hydrochar via ether and imine bonds formed with glutaraldehyde. The maximum adsorption capacities for Cr(VI) (33.663mg/g) and Ni(II) (29.059mg/g) on the modified hydrochars were 365% and 43.7% higher, respectively, than those on the unmodified hydrochar. A pseudo-second-order model described the adsorption of Ni(II) and Cr(VI) on all the adsorbents. The adsorption of Cr(VI) was endothermic, spontaneous, increased disorder, and obeyed the Langmuir model. By contrast, the adsorption of Ni(II) was exothermic, spontaneous, decreased disorder, and obeyed the Freundlich model. XPS confirmed that the adsorption sites and mechanisms for Ni(II) and Cr(VI) on the modified hydrochars were different.

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Electrostatic polymer-DNA complexes (polyplexes) have been widely investigated for DNA delivery, and remarkable differences in transfection efficacy have been seen among the materials. For example, polyethyleneimine (PEI) mediates DNA transfection more effectively than poly(l-lysine) (PLL). Biophysical properties of the polyplexes may explain their different properties in gene delivery. We investigated the structural dynamics in DNA polyplexes, especially the material exchange between the core and shell regions of the PEI and PLL polyplexes. Steady-state fluorescence spectroscopy and double labeling based fluorescence resonance energy transfer (FRET) techniques were used to study the DNA polyplexes. According to our results there is a clear difference between these two polymers: core exchange takes place in PEI but not in PLL polyplexes. Such differences in structural dynamics of polyplexes explain, at least partly, the differences in DNA release and transfection efficacy at cellular level.

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In order to increase stabilities and controlled/sustained released of T4 phages were encapsulated within alginate beads which were then coated with chitosan, polyethylene imine (PEI). Quite high loading capacities (over 90%) were achieved in these pH-sensitive microbeads. Coating with those polycations increased significantly stability both in "simulated gastric fluid" and bile salts especially in the case of PEI coating. The tests conducted in "simulated intestinal fluid" demonstrated that phages were released from the beads which were active at basic pH in which the release rates were smaller in case of chitosan. PEI concluded to be a better coating then chitosan.

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Cationized pullulan (pullulan-PEI; PP) was synthesized and further modified with an anti-oxidant molecule, ascorbic acid (PPAA) at various ratios. The nanoplexes formed at an optimum ratio of 4:1 was within a size of 150nm and had a zeta potential of 9-14mV. The nanoplexes at this ratio was used for further investigations. The cell internalization and transfection efficiency of these nanoplexes were determined in presence of serum. The internalization and transfection efficiency were found to be unaffected by the presence of fetal bovine serum. Another interesting observation was that this polymer was found to have collagen synthesis promoting property. The collagen synthesis effect of these polymers was quantified and observed that PPAA3 promoted the highest. Transfection efficiency was evaluated by assessing the p53 gene expression in C6 rat glioma cells and cell death was quantified to be 96% by flow cytometry, thus establishing the high efficacy of this polymer.

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Parkinson's disease is known to result from the loss of dopaminergic neurons. Direct intracerebral injections of high doses of recombinant glial cell line-derived neurotrophic factor (GDNF) have been shown to protect adult nigral dopaminergic neurons. Because GDNF does not cross the blood-brain barrier, intracerebral gene transfer is an ideal option. Chitosan (CHI) is a naturally derived material that has been used for gene transfer. However, the low water solubility often leads to decreased transfection efficiency. Grafting of highly water-soluble polyethylene imines (PEI) and polyethylene glycol onto polymers can increase their solubility. The purpose of this study was to design a non-viral gene carrier with improved water solubility as well as enhanced transfection efficiency for treating Parkinsonism. Two molecular weights (Mw =600 and 1,800 g/mol) of PEI were grafted onto CHI (PEI600-g-CHI and PEI1800-g-CHI, respectively) by opening the epoxide ring of ethylene glycol diglycidyl ether (EX-810). This modification resulted in a non-viral gene carrier with less cytotoxicity. The transfection efficiency of PEI600-g-CHI/deoxyribonucleic acid (DNA) polyplexes was significantly higher than either PEI1800-g-CHI/DNA or CHI/DNA polyplexes. The maximal GDNF expression of PEI600-g-CHI/DNA was at the polymer:DNA weight ratio of 10:1, which was 1.7-fold higher than the maximal GDNF expression of PEI1800-g-CHI/DNA. The low toxicity and high transfection efficiency of PEI600-g-CHI make it ideal for application to GDNF gene therapy, which has potential for the treatment of Parkinson's disease.

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The mechanisms of mucosal immunogenicity and adjuvanticity of bacterial exotoxins remains unknown. In this study, we investigated the role of the transcription factor nuclear factor-κB (NF-κB) in cholera toxin (CT)-induced alteration of oral tolerance. Feeding CT abrogated ovalbumin (OVA)-induced oral tolerance, as evaluated by OVA-specific serum antibody responses, and CD4(+) T cell proliferation. CT feeding activated canonical NF-κB (one heterodimer type, p50-p65) and mRNA expression of NF-κB-dependent proinflammatory cytokines in mesenteric lymph node (MLN) and Peyer's patch (PP) cells. CT no longer showed abrogation of oral tolerance in mice pretreated with p50 small interfering RNAs (siRNAs). ADP-ribosylation inhibitors inhibited CT-induced NF-κB activation. These data suggest that CT induces canonical NF-κB activation in intestinal lymphoid cells, which plays a key role in mucosal immunogenicity and adjuvanticity.

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Melanoma, occurring as a rapidly progressive skin cancer, is resistant to current chemo- and radiotherapy, especially after metastases to distant organs has taken place. Most chemotherapeutic drugs exert their cytotoxic effect by inducing apoptosis, which, however, is often deficient in cancer cells. Thus, it is appropriate to attempt the targeting of alternative pathways, which regulate cellular viability. Recent studies of autophagy, a well-conserved cellular catabolic process, promise to improve the therapeutic outcome in melanoma patients. Although a dual role for autophagy in cancer therapy has been reported, both protecting against and promoting cell death, the potential for using autophagy in cancer therapy seems to be promising. Here, we review the recent literature on the role of autophagy in melanoma with respect to the expression of autophagic markers, the involvement of autophagy in chemo- and immunotherapy, as well as the role of autophagy in hypoxia and altered metabolic pathways employed for melanoma therapy.

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Branched polyethylenimine (25 kDa) is thiolated and compared with redox-sensitive crosslinked derivatives. Both polymers thiol contents are assessed; the thiolated polymers have 390-2300 mmol SH groups/mol, whereas the crosslinked polymers have lower thiol contents. Cytotoxicity assays show that both modified polymers give lower hemolysis than unmodified PEI. Increased thiol content increases gene transfer efficiency but also elevates cytotoxicity. Crosslinking improves plasmid DNA condensation and enhances transfection efficiency, but extensive crosslinking overstabilizes the polyplexes and decreases transfection, emphasizing the need to balance polyplex stabilization and unpacking. Thus, at low levels of crosslinking, 25 kDa PEI can be an efficient redox-sensitive carrier system.

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