Antimicrobial Peptide Mimicking Primary Amine and Guanidine Containing Methacrylamide Copolymers Prepared by Raft Polymerization.

Naturally occurring antimicrobial peptides (AMPs) display the ability to eliminate a wide variety of bacteria, without toxicity to the host eukaryotic cells. Synthetic polymers containing moieties mimicking lysine and arginine components found in AMPs have been reported to show effectiveness against specific bacteria, with the mechanism of activity purported to depend on the nature of the amino acid mimic. In an attempt to incorporate the antimicrobial activity of both amino acids into a single water-soluble copolymer, a series of copolymers containing lysine mimicking aminopropyl methacrylamide (APMA) and arginine mimicking guanadinopropyl methacrylamide (GPMA) were prepared via aqueous RAFT polymerization. Copolymers were prepared with varying ratios of the comonomers, with degree of polymerization of 35-40 and narrow molecular weight distribution to simulate naturally occurring AMPs. Antimicrobial activity was determined against Gram-negative and Gram-positive bacteria under conditions with varying salt concentration. Toxicity to mammalian cells was assessed by hemolysis of red blood cells and MTT assays of MCF-7 cells. Antimicrobial activity was observed for APMA homopolymer and copolymers with low concentrations of GPMA against all bacteria tested, with low toxicity toward mammalian cells.

Barium ferrite decorated reduced graphene oxide nanocomposite for effective electromagnetic interference shielding.

There is an increased interest in the development of high performance microwave shielding materials against electromagnetic pollution in recent years. Barium ferrite decorated reduced graphene oxide (BaFe12O19@RGO) nanocomposite was synthesized by a high energy ball milling technique and its electromagnetic properties were investigated in the frequency range of 12.4-18 GHz (Ku band). The results showed that barium ferrite (BaFe12O19) nanoparticles with an average particle size of 20-30 nm were well distributed and firmly anchored onto the surface of the reduced graphene oxide sheets. The obtained nanocomposite exhibited a saturation magnetization of 18.1 emu g(-1) at room temperature. The presence of BaFe12O19 nanoparticles in the nanocomposite enhances the space charge polarization, natural resonance, multiple scattering and the effective anisotropy energy leading to a high electromagnetic interference shielding effectiveness of 32 dB (∼99.9% attenuation) at a critical thickness of 3 mm. The results suggested that the as-prepared BaFe12O19@RGO nanocomposite showed great potential as an effective candidate for a new type of microwave absorbing material.

Preparation and in vitro evaluation of folate-receptor-targeted SPION-polymer micelle hybrids for MRI contrast enhancement in cancer imaging.

Polymer-SPION hybrids were investigated for receptor-mediated localization in tumour tissue. Superparamagnetic iron oxide nanoparticles (SPIONs) prepared by high-temperature decomposition of iron acetylacetonate were monodisperse (9.27 ± 3.37 nm), with high saturation magnetization of 76.8 emu g(-1). Amphiphilic copolymers prepared from methyl methacrylate and PEG methacrylate by atom transfer radical polymerization were conjugated with folic acid (for folate-receptor specificity). The folate-conjugated polymer had a low critical micellar concentration (0.4 mg l(-1)), indicating stability of the micellar formulation. SPION-polymeric micelle clusters were prepared by desolvation of the SPION dispersion/polymer solution in water. Magnetic resonance imaging of the formulation revealed very good contrast enhancement, with transverse (T(2)) relaxivity of 260.4 mM(-1) s(-1). The biological evaluation of the SPION micelles included cellular viability assay (MTT) and uptake in HeLa cells. These studies demonstrated the potential use of these nanoplatforms for imaging and targeting.

Antimicrobial poly(methacrylamide) derivatives prepared via aqueous RAFT polymerization exhibit biocidal efficiency dependent upon cation structure.

Antimicrobial peptides (AMPs) show great potential as alternative therapeutic agents to conventional antibiotics as they can selectively bind and eliminate pathogenic bacteria without harming eukaryotic cells. It is of interest to develop synthetic macromolecules that mimic AMPs behavior, but that can be produced more economically at commercial scale. Herein, we describe the use of aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization to prepare primary and tertiary amine-containing polymers with precise molecular weight control and narrow molecular weight distributions. Specifically, N-(3-aminopropyl)methacrylamide (APMA) was statistically copolymerized with N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) or N-[3-(diethylamino)propyl]methacrylamide (DEAPMA) to afford a range of (co)polymer compositions. Analysis of antimicrobial activity against E. coli (Gram-negative) and B. subtilis (Gram-positive) as a function of buffer type, salt concentration, pH, and time indicated that polymers containing large fractions of primary amine were most effective against both strains of bacteria. Under physiological pH and salt conditions, the polymer with the highest primary amine content caused complete inhibition of bacterial growth at low concentrations, while negligible hemolysis was observed over the full range of concentrations tested, indicating exceptional selectivity. The cytotoxicity of select polymers was evaluated against MCF-7 cells.

Sulfonated poly(ether ether ketone) [SPEEK] nanocomposites based on hybrid nanocarbons for the detection and discrimination of some lung cancer VOC biomarkers.

The analysis of a volatolome is a promising approach to allow the early diagnosis of diseases such as cancers. However, one important challenge is to take the chemical fingerprint of the complex blend of volatiles, for many of them only present at the sub-ppm level. We have investigated a facile route to differentiate the chemo-resistive behaviour of quantum resistive vapour sensors (vQRS) and provide them with a strong methanol selectivity by simply changing the sulfonation degree of poly(ether ether ketone) up to 85%. The hybridization of carbon nanotubes (CNTs) with fullerene (C60) structured in a 3D architecture by spray layer-by-layer (sLbL) has allowed us to boost significantly the sensitivity of sensors to reach the sub-ppm level (340 ppb). After their integration into an e-nose, PEEK-nanocarbon sensors were found to effectively discriminate both single and binary mixtures of volatile organic compounds (VOCs) and among all biomarkers to detect preferentially methanol with a high signal to noise ratio (200).

Folic acid and trastuzumab conjugated redox responsive random multiblock copolymeric nanocarriers for breast cancer therapy: In-vitro and in-vivo studies.

The study represents synthesis, characterization and biological evaluation of redox responsive polymeric nanoparticles based on random multiblock copolymer for doxorubicin delivery in breast cancer. The random multiblock copolymer was synthesized via ring opening polymerization of lactide with polyethylene glycol to form triblock copolymer followed by isomerization polymerization of the triblock copolymer and 2-hydroxyethyl disulfide with the help of hexamethylene diisocynate in presence of dibutyltin dilaurate as a catalyst. Folic acid was conjugated to hydroxyl group from the multiblock polymer through DCC-NHS coupling. High drug loading content of ∼22% was achieved in the polymeric nanoparticles with size range of ∼110nm and polyethylene glycol fraction of ∼18% in the multiblock copolymer. Drug release profile confirmed the redox responsive behavior of polymeric nanoparticles with ∼72% drug release at pH 5.5 in presence of 10mM GSH as compared to ∼18% drug release at pH 7.4. In vitro cellular uptake studies showed ∼22% cellular uptake with dual (folic acid and trastuzumab) conjugated polymeric nanoparticles as compared to non-targeted polymeric nanoparticles. Fluorescence activated cell sorting (FACS) studies demonstrated higher apoptosis (∼80%) as compared to non-conjugated polymeric nanoparticles (20%) in MCF-7 cell line. In vivo studies showed 91% tumor regression in Ehrlich ascites tumor (EAT) as compared to free doxorubicin treated mice without showing any significant toxicity. Thus, it is envisaged that these redox responsive polymeric nanocarriers act as Trojan horses in cancer therapeutics.

pH- and Metal Ion- Sensitive Hydrogels based on N-[2-(dimethylaminoethyl)acrylamide].

Smart hydrogels are promising materials for actuators and sensors, as they can respond to small changes in their environment with a large property change. Hydrogels can respond to a variety of stimuli, for example temperature, pH, metal ions, etc. In this article, the synthesis and characterization of polyampholyte hydrogels based on open chain ligands showing pH and metal ion sensitivity are described. Copolymer and terpolymer gels using different mixtures of monomers i.e., N-[2-(dimethylaminoethyl)acrylamide] (DMAEAAm), N,N-dimethylacrylamide (DMAAm), acrylic acid (AA) and 2-acrylamido-2-methyl-1-propanesulphonic acid (AMPS), have been synthesized. The effect of copolymer composition, i.e., the ratio and amount of ionic monomers and the degree of crosslinking on the swelling characteristics, was evaluated as a function of pH. On this basis, metal ion sensitivity measurements were performed at selected pH values. The metal ion sensitivity was measured by varying the concentration of Cu2+, Zn2+ and Ag⁺ ions under acidic pH conditions.

ROP and ATRP Fabricated Dual Targeted Redox Sensitive Polymersomes Based on pPEGMA-PCL-ss-PCL-pPEGMA Triblock Copolymers for Breast Cancer Therapeutics.

To minimize cardiotoxicity and to increase the bioavailability of doxorubicin, polymersomes based on redox sensitive amphiphilic triblock copolymer poly(polyethylene glycol methacrylate)-poly(caprolactone)-s-s-poly(caprolactone)-poly(polyethylene glycol methacrylate) (pPEGMA-PCL-ss-PCL-pPEGMA) with disulfide linkage were designed and developed. The polymers were synthesized by ring opening polymerization (ROP) of ε-caprolactone followed by atom transfer radical polymerization (ATRP) of PEGMA. The triblock copolymers demonstrated various types of nanoparticle morphologies by varying hydrophobic/hydrophilic content of polymer blocks, with PEGMA content of ∼18% in the triblock copolymer leading to the formation of polymersomes in the size range ∼150 nm. High doxorubicin loading content of ∼21% was achieved in the polymersomes. Disulfide linkages were incorporated in the polymeric backbone to facilitate degradation of the nanoparticles by the intracellular tripeptide glutathione (GSH), leading to intracellular drug release. Release studies showed ∼59% drug release in pH 5.5 in the presence of 10 mM GSH, whereas only ∼19% was released in pH 7.4. In cellular uptake studies, dual targeted polymersomes showed ∼22-fold increase in cellular uptake efficiency in breast cancer cell lines (BT474 and MCF-7) as compared to nontargeted polymersomes with higher apoptosis rates. In vivo studies on Ehrlich's ascites tumor (EAT) bearing Swiss albino mouse model showed ∼85% tumor regression as compared to free doxorubicin (∼42%) without any significant cardiotoxicity associated with doxorubicin. The results indicate enhanced antitumor efficacy of the redox sensitive biocompatible nanosystem and shows promise as a potential drug nanocarrier in cancer therapeutics.

The effect of composition of poly(acrylic acid)-gelatin hydrogel on gentamicin sulphate release: in vitro.

Hydrogels based on poly(acrylic acid) and gelatin crosslinked with N,N'-methylene bisacrylamide (0.5mol%) and glutaraldehyde (4%), respectively, forming an interpenetrating network were employed as matrices, for studying the loading and release of gentamicin sulphate. The release kinetics of gentamicin sulphate was evaluated in water (pH approximately 5.8), phosphate buffer (pH 7.4) and citrate buffer (pH 4) at 37+/-0.1 degrees C. The drug release in phosphate buffer was faster as compared to water or citrate buffer. Fitting the data of release studies in Peppas model indicated that the release of drug from full IPNs in phosphate buffer (pH 7.4), water (pH approximately 5.8) and citrate buffer (pH 4) were diffusion controlled. However, semi-IPNs showed both anomalous and Fickian diffusion mechanisms. With increasing gelatin percentage in the polymer, rate of drug release was faster and almost 85% of the loaded drug was released within 7 days in phosphate buffer (pH 7.4).

Studies on biodegradation and release of gentamicin sulphate from interpenetrating network hydrogels based on poly(acrylic acid) and gelatin: in vitro and in vivo.

Interpenetrating network hydrogels (IPNs) based on poly(acrylic acid) and gelatin (Ge) were evaluated for in vitro and in vivo biodegradation and in vivo release of gentamicin sulphate. In vitro and in vivo degradation studies demonstrated that with the increase of acrylic acid content in the polymer, the rate of degradation decreases, and a reverse phenomenon was observed with increasing Ge content in the hydrogel. The rate of in vivo degradation was much lower than in vitro degradation. Incorporation of gentamicin sulphate in hydrogel further reduces their degradation. In vitro and in vivo drug release profile showed a burst effect, followed by controlled release. Drug concentration was measured in the local skin tissue, blood serum, kidney, liver and spleen. The local skin tissue concentration of 50% and 100% gentamicin sulphate, loaded full IPNs (i.e., Ax-1 and Ax-2), was found to be higher (20+/-2mug/g) than the minimum bactericidal concentration for Staphylococcus aureus (1.2mug/g) and Pseudomonas aeruginosa (10mug/g), respectively, for a study time of 60 days.

Ultrasensitive QRS made by supramolecular assembly of functionalized cyclodextrins and graphene for the detection of lung cancer VOC biomarkers.

A novel electronic nose system comprising functionalized ß-cyclodextrin wrapped reduced graphene oxide (RGO) sensors with distinct ability of discrimination of a set of volatile organic compounds has been developed. Non-covalent modification of chemically functionalized cyclodextrin with RGO is carried out by using pyrene adamantane as a linker wherever necessary, in order to construct a supramolecular assembly. The chemical functionality on cyclodextrin is varied utilising the principle of selective chemical modification of cyclodextrin. In the present study, the combined benefits of the host-guest inclusion complex formation ability and tunable chemical functionality of cyclodextrin, as well as the high surface area and electrical conductivity of graphene, are utilized for the development of a set of highly selective quantum resistive chemical vapour sensors (QRS), which can be assembled in an electronic nose.

High permittivity polyaniline-barium titanate nanocomposites with excellent electromagnetic interference shielding response.

Organic conductive polymers are at the forefront of materials science research because of their diverse applications built around their interesting and unique properties. This work reports for the first time a correlation between the structural, electrical, and electromagnetic properties of polyaniline (PANI)-tetragonal BaTiO3 (TBT) nanocomposites prepared by in-situ emulsion polymerization. XRD studies and HRTEM micrographs of these nanocomposites clearly revealed the incorporation of TBT nanoparticles in the conducting PANI matrix. EPR and XPS measurements reveal that increase in loading level of BaTiO3 results in a reduction of the doping level of PANI. The Ku-Band (12.4-18 GHz) network analysis of these composites shows exceptional microwave shielding response with absorption dominated total shielding effectiveness (SET) value of -71.5 dB (blockage of more than 99.99999% of incident radiation) which is the highest value reported in the literature. Such a high attenuation level, which critically depends on the fraction of BaTiO3 is attributed to optimized dielectric and electrical attributes. This demonstrates the possibility of using these materials in stealth technology and for making futuristic radar absorbing materials (RAMs).

Comparative evaluation of residual monomer content and polymerization shrinkage of a packable composite and an ormocer.

AIM: The aim of this study is to evaluate the residual monomer content and polymerization shrinkage of a packable composite (Surefil) and an ormocer (Admira). MATERIALS AND METHODS: The study was conducted in two parts. In Part I, 10 samples of each material were prepared in a standardized split brass mould, using incremental curing technique. The residual monomer content was measured by observing change in weight before and after Soxhlet Extraction procedure. In part II, the volumetric polymerization shrinkage was calculated by measuring the difference in specific gravities of 10 uncured and 10 cured samples of each material using a modified version of ASTM D-792 method. The data obtained was put to statistical analysis using student's 't' test. RESULTS: Part I - The percentage change in weight for Surefil was 0.525% while that for Admira was 0.374%, which was found to be statistically significant. Part II - The volumetric percentage shrinkage for Surefil ranged between 1.04-3.42% and that for Admira between 1.01-2.31%, which was not found to be significant statistically. CONCLUSION: Admira may be considered more biocompatible than Surefil due to the lower residual monomer content in the former; however, both are comparable with regards to their polymerization shrinkage.

Interpenetrating polymer network (IPN) nanogels based on gelatin and poly(acrylic acid) by inverse miniemulsion technique: synthesis and characterization.

Novel interpenetrating polymer network (IPN) nanogels composed of poly(acrylic acid) and gelatin were synthesised by one pot inverse miniemulsion (IME) technique. This is based on the concept of nanoreactor and cross-checked from template polymerization technique. Acrylic acid (AA) monomer stabilized around the gelatin macromolecules in each droplet was polymerized using ammonium persulfate (APS) and tetramethyl ethylene diamine (TEMED) in 1:5 molar ratio and cross-linked with N,N-methylene bisacrylamide (BIS) to form semi-IPN (sIPN) nanogels, which were sequentially cross-linked using glutaraldehyde (Glu) to form IPNs. Span 20, an FDA approved surfactant was employed for the formation of homopolymer, sIPN and IPN nanogels. Formation of stable gelatin-AA droplets were observed at 2% surfactant concentration. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) studies of purified nanogels showed small, spherical IPN nanogels with an average diameter of 255 nm. In contrast, sIPN prepared using the same method gave nanogels of larger size. Fourier-transform infrared (FT-IR) spectroscopy, SEM, DLS, X-ray photoelectron spectroscopy (XPS) and zeta potential studies confirm the interpenetration of the two networks. Leaching of free PAA chains in sIPN upon dialysis against distilled water leads to porous nanogels. The non-uniform surface of IPN nanogels seen in transmission electron microscopy (TEM) images suggests the phase separation of two polymer networks. An increase of N/C ratio from 0.07 to 0.17 (from PAA gel to IPN) and O/C ratio from 0.22 to 0.37 (from gelatin gel to IPN) of the nanogels by XPS measurements showed that both polymer components at the nanogel surface are interpenetrated. These nanogels have tailoring properties in order to use them as high potential drug delivery vehicles for cancer targeting.