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\nImpact StatementsPoly(L-lysine)-block-poly(ethylene glycol)-block-poly(L-lysine) (PLys-block-PEG-block-PLys) triblock copolymers formed polyion complex (PIC) with poly(acrylic acid) (PAAc) or sodium poly(styrenesulfonate) (PSS), leading to the formation of flower micelle-type nanoparticles (NanoLys/PAAc or NanoLys/PSS) with tens of nanometers size in water at a polymer concentration of 10 mg/mL. The flower micelles exhibited irreversible temperature-driven sol-gel transitions at physiological ionic strength, even at low polymer concentrations such as 40 mg/mL, making them promising candidates for injectable hydrogel applications. Rheological studies showed that the chain length of PLys segments and the choice of polyanions significantly impacted irreversible hydrogel formation, with PSS being superior to PAAc for the formation. The incorporation of silica gel nanoparticles into the PIC flower micelles also resulted in irreversible gelation phenomena. The highest storage modulus exceeded 10 kPa after gelation, which is sufficient for practical applications. This study demonstrates the potential of these PIC-based hydrogels as biomaterials with tunable properties for biomedical applications.A polyion complex-based flower micelle, formed by poly(L-lysine)-block-PEG-block- poly(L-lysine) triblock copolymers and polyanions, shows irreversible hydrogel formation; incorporating silica enhanced its modulus to exceeding 10 kPa, promising for biomedical applications. [ABSTRACT FROM AUTHOR]

The polyion complexes (PICs) between plasmid DNA (pDNA) and succinylated branched polyethylenimine (bPEI-Et-COOH) were formed for in vivo pDNA delivery by muscular injection. Transmission electron microscopy (TEM) observation revealed that the PIC between pDNA and bPEI-Et-COOH with higher succinylated degree formed the particle structure with corona-like shell. Furthermore, confocal laser scanning microscopy (CLSM) observation revealed that pDNAs were successfully delivered inside the cells and that the pDNAs were colocalized with the nuclei of the cells after endosomal escape. Although the pDNA/bPEI-Et-COOH PICs mediated significant gene expression in vitro, the PICs did not mediate gene expression in vivo muscular injection. Consequently, the pDNA transfection by bPEI-Et-COOH was noncorrelative between in vitro and in vivo in spite of low toxicity by succinylation both in vitro and in vivo. The noncorrelative relation between in vitro and in vivo for pDNA transfection by bPEI-Et-COOH muscular injection would be considerable design for pDNA carriers in vivo. [ABSTRACT FROM AUTHOR]

Degradability of polycations under physiological conditions is an attractive feature for their use in biomedical applications, such as the delivery of nucleic acids. This study aims to design polycations with tunable nonenzymatic degradability. A series of cationic N-substituted polyaspartamides were prepared to possess primary amine via various lengths of alkyl spacers in side chains. The degradation rate of each polyaspartamide derivative was determined by size exclusion chromatography under different pH conditions. The N-substituted polyaspartamide containing a 2-aminoethyl moiety in the side chain (PAsp(AE)) showed considerable degradability under physiological conditions (pH 7.4, 37 °C). In contrast, the N-substituted polyaspartamides bearing a longer alkyl spacer in the side chain, i.e. the 3-aminopropyl (PAsp(AP)) and 4-aminobutyl moieties (PAsp(AB)), more strongly suppressed degradation. Further, a positive correlation was observed between the degradation rate of N-substituted polyaspartamides and a deprotonation degree of primary amines in their side chains. Therefore, we conclude that the deprotonated primary amine in the side chain of N-substituted polyaspartamides can induce the degradation of the main chain through the activation of amide nitrogen in the side chain. When N-substituted polyaspartamides were utilized as a messenger RNA (mRNA) delivery vehicle via formation of polyion complexes (PICs), degradable PAsp(AE) elicited significantly higher mRNA expression efficiency in cultured cells compared to PAsp(AP) and PAsp(AB). The higher efficiency of PAsp(AE) might be due to the facilitated destabilization of PICs within the cells, directed toward mRNA release. Additionally, degradation of PAsp(AE) considerably reduced its cytotoxicity. Thus, our study highlights a useful design of well-defined cationic poly(amino acid)s with tunable nonenzymatic degradability. [ABSTRACT FROM AUTHOR]

Surface functionalization of nanoparticles is a crucial factor for nanoparticle-mediated drug and nucleic acid delivery. Particularly, the density of targeting ligands on nanoparticle significantly affects the affinity of nanoparticles to specific cellular surface (or receptor) through the multivalent binding effect. Herein, multilayered polyion complexes (mPICs) are prepared to possess varying densities of cyclic RGD peptide (cRGD) ligands for cancer-targeted small interfering RNA (siRNA) delivery. A template PIC is first prepared by mixing siRNAs with homo catiomers of N-substituted polyaspartamide bearing tetraethylenepentamine (PAsp(TEP)) in aqueous solution, followed by silica-coating through silicate condensation reaction. Then, silica-coated PICs (sPICs) are further covered with block catiomers of PAsp(TEP) and poly(ethylene glycol) (PEG) equipped with cRGD ligand. Successful preparation of targeted mPICs is confirmed from the changes in size and ζ-potential and the elemental analysis by transmission electron microscopy. Notably, the number of cRGD ligands per mPIC is regulated by altering the silicate concentration upon preparation of sPICs, which is confirmed by fluorescence correlation spectroscopy using fluorescent-labeled block catiomers. Ultimately, the targeted mPICs with a higher number of cRGD ligands demonstrate more efficient cellular uptake in cultured cancer cells, leading to enhanced gene silencing activity. [ABSTRACT FROM AUTHOR]

This research focuses on the preparation of polyion complex having spironaphthoxazine and their photochromic behaviors including absorbance and fluorescence switching. The polyion complex was prepared by the ion complex formation between spironaphthoxazine 3 (cationic monomer) and poly(styrene-sulfonic acid) (anionic polymer). Spironaphthoxazine group showed reversible photoisomerization in this polyion complex upon UV irradiation. It reversibly changed the fluorescent intensity by alternative irradiation with ultraviolet and visible light. The photoinduced ionic conductivity in polyion complex solution gradually increased upon UV irradiation and subsequently decreased in the dark. [ABSTRACT FROM AUTHOR]

A novel hyaluronic acid (HA)-based hydrogel was prepared through polyion complex (PIC) formation between cationic polylactide (PLA)-based microspheres (MS+) and hyaluronic acid (HA-) as an anionic polyelectrolyte. The MS+ and HA formed a biodegradable PIC hydrogel (HA-/MS+) when mixed in aqueous media. The swelling behavior and mechanical properties of the PIC hydrogel could be controlled by changing the charge ratio between HA- and MS+. In addition, the HA-/MS+ PIC hydrogel resulted in a lower inflammatory response compared with a collagen hydrogel in vivo. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the utility of mixtures among oppositely charged dextran derivatives as constituents of a controlled release microsphere. Carboxymethyldextran (CMD) and dextran sulfate (DS) were used as polyanions, and [2-(diethylamino) ethyl] dextran (EA) and [2-hydroxypropyltrimethylammonium] dextran (CDC) as polycations. The microspheres consisting of hydrophilic and hydrophobic polymers were prepared by emulsion-solvent evaporation method. The mixtures, CMD/EA, CMD/CDC, DS/EA, and DS/CDC, were used as hydrophilic polymers, because they can interact with each other to form polyion complexes for the improvement of sustained-release performances. Cellulose acetate butyrate and theophylline were used as a model hydrophobic polymer and a model drug, respectively. The yield of microspheres was excellent (more than 95%). According to observation, by scanning election microscopy (SEM) microspheres were spherical with a rough surface. The in vitro drug release from microspheres was examined in the JP XIV first fluid, pH 1.2, and second fluid, pH 6.8, at 37°C, and 100 rpm. In the DS/CDC system, drug release was depressed by formation of a polyion complex and not affected by pH of dissolution medium. The release rate was modulated by the ratio of hydrophilic and hydrophobic matrix. This particulate system, in which the polyion complex matrix is strengthened by a hydrophobic polymer, is a promising formulation for drug delivery. [ABSTRACT FROM AUTHOR]

The human lymphocytes were interacted with polymer surfaces whose surface potential was controlled by the formation of a polyion complex (PIC) having a phosphorylcholine moiety. 3-(Methacryloyloxypropyl)-trimethyl ammonium iodide as the cationic unit or potassium 3-methacryloyloxypropyl sulfonate as the anionic unit was copolymerized with 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butyl methacrylate. PIC was made at the solid–liquid interface, that is, an aqueous solution containing an anionic polymer with different concentrations was contacted with a cationic polymer coated polymer membrane. The formation process of PIC was followed using a quartz crystal microbalance, and the PIC surfaces were analyzed by ζ-potential and X-ray photoelectron spectroscopy. The surface potential on the PIC was controllable from +20 to −16 mV, which increased in the amount of adsorbed anionic copolymer as the ζ-potential decreased toward the negative charge. The PIC surface in contact with human lymphocyte for 5 h was observed using a scanning electron microscopy and the density of the adherent human lymphocyte was determined by the lactate dehydrogenase method. The lymphocyte adhesion on the surface was gradually reduced with an increase in the negative value of the ζ-potential. The morphological change in the adherent lymphocytes was not observed on the polymer surfaces with MPC units. The adherent lymphocytes were not activated on the PIC surface. The lymphocyte adhesion with reduced activation could be controlled by changing the surface potential on the polymer with the MPC unit. [Copyright &y& Elsevier]

Gelatin was anionized to increase the carboxylic acid groups through succinylation. Succinylation of gelatin was performed using varying amounts of succinic anhydride. This gave various percentages of substitution. Lysozyme, a cationic antibacterial enzyme, which has important applications in the reduction of prosthetic valve endocarditis, was chosen as a model protein drug. Microspheres were prepared using unmodified gelatin and succinylated gelatin (SG) and lysozyme was incorporated into them. The percentage loading and release profiles of lysozyme for gelatin and SG microspheres were evaluated and compared. It was found that the SG microspheres exhibited higher loading efficiency for lysozyme (50%) than the unmodified gelatin microspheres. The in vitro release of lysozyme from SG microspheres occurred up to 122 h, compared to 96 h for gelatin microspheres, for the release of most of the lysozyme incorporated. This prolonged release of lysozyme from SG microspheres was attributed to the electrostatic interaction between the cationic lysozyme and the anionic SG microsphere carrier. [ABSTRACT FROM AUTHOR]