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Akhil K Mohan,1,2 Minsa M,3 T R Santhosh Kumar,3 G S Vinod Kumar1 1Nano Drug Delivery Systems (NDDS), Cancer Biology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, India; 2Research Centre, Department of Biotechnology, University of Kerala, Thiruvananthapuram, Kerala, India; 3Cancer Research Programme-1, Bio-Innovation Center (BIC), Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, IndiaCorrespondence: G S Vinod Kumar, Tel +91 471 2781217, Fax +91 471 2348096, Email gsvinod@rgcb.res.inPurpose: Peptide-based therapy is a promising strategy for cancer treatment because of its low drug resistance. However, the major challenge is their inability to target cancer cells specifically. So, a targeted nano-delivery system that could deliver therapeutic peptides selectively to cancer cells to stimulate their action is highly desirable. This study aims to deliver the antitumor peptide, Pep5, to breast tumor cells selectively using a targeting peptide functionalised multi-layered PLGA-PEI nanoparticles.Methods: In this study, Pep5 entrapped PLGA-PEI (Pep5-PPN) dual layered nanoparticles were developed. These nanoparticles were decorated with TKD (Pep5-TPPN) on their surface for site-specific delivery of Pep5 to breast tumor cells. The particles were then characterized using various instrumental analyses. In vitro cytotoxicity of the particles was evaluated in estrogen receptor positive (ER+ve) and triple negative breast cancer (TNBC) cells. An ex vivo tumor spheroid model was used to analyze the antitumor activity of the particles.Results: Uniformly round Pep5-TPPN particles were synthesized with an average diameter of 420.8 ± 14.72 nm. The conjugation of PEI over Pep5-PLGA nanoparticles shifted the zeta potential from − 11.6 ± 2.16 mV to +20.01 ± 2.97 mV. In vitro cytotoxicity analysis proved that TKD conjugation to nanoparticles enhanced the antitumor activity of Pep5 in tested breast cancer cells. Pep5-TPPN induced cytoskeletal damage and apoptosis in the tested cells, which showed that the mechanism of action of Pep5 is conserved but potentiated. Active targeting of Pep5 suppressed the tumor growth in ex vivo spheroid models.Conclusion: A multi-layered nanoparticle functionalized with dual peptide was fabricated for active tumor targeting, which stimulated Pep5 activity to reduce the tumor growth in vitro and ex vivo.Graphical Abstract: Keywords: peptide, Pep 5, tumor, cancer, breast

We have investigated the wound healing efficiency of calcium alginate wafer embedded with growth factor entrapped PLGA nanoparticle. Herein, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) entrapped PLGA nanoparticles were synthesized and embedded in a sodium alginate gel by freeze-drying technique. The synthesized dressing exhibited a high degree of swelling and appropriate porosity. The scaffold was characterized by Scanning Electron Microscopy (SEM) showing a highly porous morphology. Also, incorporation of growth factor loaded nanoparticles in a wafer-based delivery system resulted in localized growth factor delivery at the site of the wound in a sustained manner. The biocompatibility of the scaffold was evaluated by MTT assay, which showed a higher cell proliferation in the proposed scaffold as compared to the control. In vivo wound healing efficiency of the scaffold was evaluated using a full thickness murine wound model, which showed improved re-epithelialization, collagen deposition, and angiogenesis. These results suggest the use of the scaffold as a promising wound dressing material.

Teena Jacob Chirayil,1,2 G S Vinod Kumar1 1Nano Drug Delivery Systems (NDDS), Cancer Biology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India; 2Research Scholar, Department of Biotechnology, University of Kerala, Thiruvananthapuram, Kerala, IndiaCorrespondence: G S Vinod Kumar, Tel +91 471 2781217, Email gsvinod@rgcb.res.inPurpose: This study aimed to design a prototypic drug delivery system (DDS) made of an amphiphilic, pullulan (Pull)-derived biodegradable polymer for targeting the asialoglycoprotein receptor (ASGPR) overexpressed in HCC. Stearic acid (SA) was conjugated to increase the hydrophobicity of pullulan (Pull-SA).Methods: Pullulan (Pull) was linked to stearic acid (SA) after functional group modifications via EDC/NHS chemistry and characterized. Sorafenib tosylate (SRFT) was entrapped in pullulan–stearic acid nanoparticles (Pull-SA-SRFT) and its particle size, zeta potential, entrapment efficiency (EE), loading capacity (LC), and release efficiency was measured. The competence of Pull-SA-SRFT over SRFT in vitro was assessed using the ASGPR over-expressing PLC/PRF/5 hepatocellular carcinoma (HCC) cell line. This was done by studying cytotoxicity by MTT assay and chromosome condensation assay, early apoptosis by annexin-Pi staining, and late apoptosis by live–dead assay. The cellular uptake study was performed by incorporating coumarin-6 (C6) fluorophore in place of SRFT in Pull-SA conjugates. A biodistribution study was conducted in Swiss-albino mice to assess the biocompatibility and targeting properties of SRFT and Pull-SA-SRFT to the liver and other organs at 1, 6, 24, and 48 h.Results: The characterization studies of the copolymer confirmed the successful conjugation of Pull-SA. The self-assembled amphiphilic nanocarrier could proficiently entrap the hydrophobic drug SRFT to obtain an entrapment efficiency of 95.6% (Pull-SA-SRFT). Characterization of the synthesized nanoparticles exhibited highly desirable nanoparticle characteristics. In vitro, apoptotic studies urged that Pull-SA-SRFT nanoparticle was delivered more efficiently to HCC than SRFT. The cellular uptake study performed, gave propitious results in 4 hrs. The biodistribution study conducted in immunocompetent mice suggested that Pull-SA-SRFT was delivered more than SRFT to the liver when compared to other organs, and that the system was biocompatible.Conclusion: Pull-SA-SRFT is a promisingly safe, biodegradable, cell-specific nanocarrier and a potential candidate to target hydrophobic drugs to HCC.Graphical Abstract: Keywords: pullulan stearic acid nanoparticles, hepatocellular carcinoma, drug delivery system

The present work reports on foaming of magnesium alloys and composites using MgCO3 as the blowing agent. Foaming was done via the molten metal route by direct addition of MgCO3 in molten Mg. The alloys and composites required for foaming were prepared by varying the concentration of aluminum (10 to 30 wt pct) and calcium (0 and 2 wt pct) in Mg. SiC of 10-µm size and about 10 to 20 vol pct was added as reinforcement particles in the composite. The liquidus temperature of the alloys and composites, the decomposition behavior of MgCO3, and the intrinsic oxides that formed in the melt have a significant effect on the structure of the foams. Mg alloys and composites with 30 wt pct Al showed better foaming behavior with higher expansion, lower density, good cell structure, and uniform cell size distribution due to the smaller difference between their liquidus temperature and the decomposition temperature of MgCO3. The addition of 2 wt pct Ca showed a significant effect on foaming, and the MgO and MgAl2O4 (spinel) particles formed in situ in the molten Mg during foaming acted as the stabilizing agents.

Polymeric nanofibrous scaffolds provide fine-tuned structures with inter-connecting pores resembling the natural extracellular matrix (ECM) in tissues, and show good potential in assisting the creation of artificial functional tissue. Additional application of growth factors helps to regulate the cellular behaviors and tissue assembly in the scaffolds, which eases the healing process. In this study, we synthesized an electrospun polymer scaffold system enriched with nanoparticles containing growth factors for accelerated healing of diabetic wounds. BSA nanoparticles were synthesized by cross-linking with PEG aldehyde. To free the amino group of BSA, heparin was conjugated by EDC/NHS chemistry. The angiogenic growth factors bFGF and VEGF were bound to heparin by electrostatic interaction. These nanoparticles were adsorbed on to electrospun collagen/PLGA/chitosan nanofibers. The synthesized nanofiber system was evaluated in vitro for its cell viability and proliferation. In vivo experiments conducted in a streptozotocin-induced diabetic mice model showed accelerated wound healing. The excellent healing efficiency of this ECM-mimicking nanofiber scaffold makes it a great candidate for therapeutic application in diabetic wounds.

This project aims to investigate and predict the optimal choice for each EDM parameter using Taguchi Method by conducting a limited number of experiments on “Nimonic” Material. These parameters have a significant influence on the machining characteristics like MRR and TWR. Taguchi design of experiments (DOE) are implemented, particularly L9 orthogonal array is chosen and the effect of dominating process parameters is evaluated using analysis of variance. Nimonic refers to a family of Nickel-based high-temperature low creep superalloys. Due to its ability to withstand very high temperatures, Nimonic is ideal for typical applications such as aircraft parts, gas turbine components and blades, exhaust nozzles etc., for instance, where the pressure and heat are extreme. However, the conventional methods are not suitable to machine the hardest material such as Nimonic superalloy. The EDM, one of the popular unconventional machining methods, is used to the machine with a copper electrode, which in turn uses Taguchi methodology to analyze the effect of each parameter on the machining characteristics. The optimal choice for each EDM parameter such as peak current, gap voltage, duty cycle and pulse on time using the Taguchi method and Genetic Algorithm are identified. These parameters have a significant influence on machining characteristics such as MRR, EWR and surface roughness.

In the present work, Al-4 wt pct Cu/TiC composite was synthesized by the molten salt route that contains submicron-sized TiC particles in the Al-4 wt pct Cu matrix. The concentration of the TiC particle in the base alloy is 7.5 wt pct. Melt ultrasound treatment was done by remelting the as-cast composite at 1023 K (750 °C) in a view to refine the size of TiC particles to nanoscale and distribute them evenly in the matrix. The microstructure and age hardenability of the untreated and ultrasound-treated composites were investigated. The TiC particles accelerate the precipitation kinetics of CuAl2 phase in Al-4 wt pct Cu alloy. In the present study, the hardness obtained for untreated Al-4 wt pct Cu/TiC composite is 120 VHN within 5 hours of peak aging time, which is higher than the hardness of the monolithic Al-4 wt pct Cu, which is 104 VHN at 35 hours of peak aging time. Melt ultrasound treatment of Al-4 wt pct Cu/TiC composite shows no significant effect on the distribution and refinement of TiC particles in the matrix. However, it partially disintegrates the TiC into Al3Ti and Al4C3 particles. The ultrasound-treated composite showed an improved hardness of about 132 VHN at 5 hours of peak aging, in comparison to that of the untreated composite, by forming denser and homogeneous CuAl2 precipitates.

The paper aims to investigate standalone FeCoCrNi2Al, FeCoCrNiAl0.3, FeCoNiAlTi0.4 and NiCoCrAlSi high entropy alloys (HEA) as a possible bond coat material for thermal barrier coating (TBC) system. For this high entropy alloys prepared by mechanical activated synthesis (MAS) were densified by spark plasma sintering (SPS). MAS HEAs were investigated for phase formation, melting temperature and coefficient of thermal expansion by X-ray diffractometer (XRD), Differential scanning calorimetry (DSC) and Dilatometer respectively. Isothermal oxidation of sintered samples was carried out at 1050 °C for a period of 5, 25, 50, 100, 200 and 300 h in the air. The formation and growth of thermally grown oxides (TGO) were investigated by Raman spectroscopy, X-Ray Diffraction, and Scanning electron microscopy (SEM). The oxidation study shows that FeCoCrNi2Al and FeCoNiAlTi0.4 HEA follow parabolic rate weight gain due to the formation of TGO enriched in Al2O3. Discontinuous weight changes due to the formation of CoAl2O4, NiCrFeO4, and Cr2O3 phases were observed in FeCoCrNiAl0.3 HEA. TGO enriched in Al2O3 and NiAl2O4 were observed in NiCoCrAlSi HEA, whereas FeCoNiAlTi0.4 HEA shows the formation of TGO enriched in Al2O3, NiAl2O4, Ti2O3, and Al2O5Ti. Increase in coefficient of thermal expansion (CTE) with increasing temperature is observed for FeCoCrNi2Al and FeCoNiAlTi0.4 HEA. FeCoCrNi2Al HEA showing average CTE of 15.16 ± 0.25 × 10−6/K, good mechanical properties, and containing α-alumina TGO layer, makes it a potential candidate for a bond coat material.

Background Treatment of wounds with the help of nanoparticles (NPs) is more effective and superior in comparison to traditional wound healing methods as it protects and sustains active drug release at the wound site thus enhancing the safety of the drug and reducing the possibility of side effects. The advantages of this method are the possibility of allowing a reduction in administered dose, limiting toxicity levels to the minimum, and increasing safety of topical delivery of the drug. Materials and methods We report the synthesis of a novel poly (lactic-co-glycolic acid) (PLGA) NP-based multicargo delivery system for growth factors and antimicrobial peptide. Growth factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were entrapped in PLGA NPs by solvent diffusion method and an antimicrobial peptide (K4) was conjugated to the NP by carbodiimide chemistry. The developed multiple cargo delivery systems with growth factors (VEGF and bFGF) and an antimicrobial peptide (K4) were investigated and optimized for potential wound healing. Results The system showed a sustained release of growth factors and was evaluated for cytotoxicity by MTT and live/dead assay, which revealed that the bioactivity of the growth factor-entrapped NPs was higher than that of free growth factors, and it also induced enhanced cell proliferation in vitro. Conclusion The development of a system for the codelivery of growth factors (VEGF and bFGF) and an antimicrobial peptide (K4) was investigated for potential wound healing application. The entrapment of growth factors with very high efficiency is an advantage in this method along with its sustained release from the nanoparticulate system, which will enhance the angiogenesis. Our system also displayed broad-spectrum antimicrobial activity against both gram-positive and gram-negative bacteria.

Closed-cell foams were produced from re-melted aluminum alloy scrap that contained 0.13 wt pct Mg magnesium in the as-received state and higher levels after adding 1, 2, or 5 wt pct Mg. The excess Mg gave rise to the fragmentation of long oxide filaments present in the scrap alloy into smaller filaments and improved its distribution and wetting by the Al matrix. Foaming the re-melted scrap alloy containing 1, 2, and 5 wt pct Mg excess showed stability and good expansion in comparison to the scrap alloy containing 0.13 wt pct Mg only, but the cells became non-equiaxed when the Mg concentration was high (≥2 wt pct excess) due to cell wall rupture during solidification. Compressibility and energy absorption behavior were studied for scrap alloy foams containing 1 wt pct Mg excess, which is the optimum level to obtain good expansion, stability, and uniform cell size. Foams with densities in the range of 0.2 to 0.4 g cm−1 produced by holding at the foaming temperature for different times were used for the investigation. A uniform cell structure led to flatter stress plateaus, higher energy absorption efficiencies, and reduced “knockdown” in strength compared with commercial foams made by gas bubbling. The mechanical performance found is comparable to that of commercial foams made by a similar method but the expected costs are lower.

Application of growth factors at wound site has improved the efficiency and quality of healing. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) induce proliferation of various cells in wound healing. Delivery of growth factor from controlled release systems protect it from degradation and also result in sustained delivery of it at the site of injury. The goal of the study was to develop a Polyethylene glycol (PEG) cross-linked cotton-like chitosan scaffold (CS-PEG-H) by freeze-drying method and chemically conjugate heparin to the scaffold to which the growth factors can be electrostatically bound and evaluate its wound healing properties in vitro and in vivo. The growth factor containing scaffolds induced increased proliferation of HaCaT cells, increased neovascularization and collagen formation seen by H and E and Masson’s trichrome staining. Immunohistochemistry was performed using the Ki67 marker which increased proliferation of cells in growth factor containing scaffold treated group. Frequent dressing changes are a major deterrent to proper wound healing. Our system was found to release both VEGF and bFGF in a continuous manner and attained stability after 7 days. Thus our system can maintain therapeutic levels of growth factor at the wound bed thereby avoiding the need for daily applications and frequent dressing changes. Thus, it can be a promising candidate for wound healing.

This interdisciplinary research highlights the engineering of glycolipid nanomicelles with surface modification using a BBB crossing peptide for in vivo drug delivery especially for glioma therapy. We demonstrated an eco-friendly, green synthesis of a nanomicelle followed by felicitous characterization which substantiates the merits of the drug delivery system.

Very few successful interventions have been possible in glioma therapy owing to its aggressive nature as well as its hindrance of targeted therapy together with the limited access afforded by the blood-brain barrier (BBB). With the advent of nanotechnology based delivery vehicles such as micelles, dendrimers, polymer-based nanoparticles and nanogels, the breach of the BBB has been facilitated. However, there remains the issue of targeted therapy for glioma cells. Peptide-mediated surface modification of nanocarriers serves this purpose, extending the ability to target glioma further than the enhanced permeability and retention effect. Areas covered: Here we have tried to re-establish the significance of peptides that could be used in various ways for treating glioma. Peptide-embellished nanocarriers used to deliver anticancer drugs; nucleic acids (siRNA, miRNA); micelles or dendrimers grafted with immunogenic glioma-derived peptides used for stimulating active immunity in vaccine therapy, glioma targets for cell penetrating peptides and homing to specific receptors are reviewed. Expert opinion: Peptides have multifunctional potential in targeting, BBB and cell penetration, and can serve as antagonists of various ligands and agonists of particular over-expressed receptors as discussed in this review. Using peptides in targeted personalized therapy would be one step forward and may offer new avenues for glioma therapeutics.

Dry powder inhalers (DPI) attracted the attention of pharmaceutical field due to its enlarging market share in inhalable formulations. These formulations also pose patient compliance and good shelf life. Earlier DPI formulations were intended for local effect in lung (asthma and chronic obstructive pulmonary diseases), whereas 21(st) century witnessed formulations intended for systemic effect too. A better understanding of physiology of lung and fluidics of air flow helped in targeting alveoli using DPI technology. Modern characterization tools also accelerated the research pace. In addition to the synthetic molecules, DPI also was proved to be a better system for delivering biological molecules including vaccines. This review includes the mechanisms of drug deposition, advancements in the fields of DPI devices, various characterization tools and particle engineering. In this review we have related the chronological advancement of inhalational technology starting from 1788 AD to the present.

Metallic foams have now reached the maturity of development in terms of process stability, materials properties and costs required for industrial applications. The fine-tuning of the manufacturing process carried out in the past few years has been responsible for this success. Nowadays, Al foam panels as large as 2.5 m × 1.5 m in area and having a uniform pore structure are commercially available. In parallel to this development, new processing routes are being explored, including foaming with novel blowing agents, foaming by application of under-pressure, foaming of scrap and of other metals such as magnesium. Some of the steps of these developments are reviewed.

In this study, it was shown that aluminum powder can be used as stabilizing particles for the fabrication of aluminum foams by melt route. When Al powder was mixed with the TiH2 before adding into the melt, it also acted as dispersing agent for the TiH2 thus further improving the structure of the foams. Stirring during powder mixing also contributed towards foam stability by introducing oxides into the melt. The oxides were examined using SEM/EDS and oxygen analyzer.

The rate of lung cancer incidence is alarmingly mounting, despite the decline of smoking and tobacco consumption. Recent reports indicate a very high correlation between the growing fast food culture and lung cancer incidence. Benzo[a]pyrene (B[a]P) is a potent carcinogen abundantly present in grilled and deep-fried food and in tobacco smoke. Our previous studies have proved the efficacy of curcumin in curbing B[a]P-induced lung carcinogenesis. However, the poor pharmacokinetic profile of the compound considerably hampers its potential as an effective chemopreventive. This study was intended to evaluate whether encapsulation of curcumin in chitosan nanoparticles can improve the cellular uptake and prolong the tissue retention of curcumin yielding better chemoprevention. The curcumin-loaded chitosan nanoparticles (chitosan nanocurcumin) exhibited a size of 170–200 nm in transmission electron microscopy. In vitro drug release studies showed sustained release of curcumin over a period of approximately 180 hours and excellent intracellular uptake and cytotoxicity in lung cancer cells. Bioavailability studies using healthy Swiss albino mice demonstrated drastic enhancement in lung localization of chitosan nanocurcumin compared with free curcumin. Toxicologic evaluation using chronic toxicity model in Swiss albino mice confirmed the pharmacologic safety of the formulation. Moreover, the formulation, even at a dose equivalent to one fourth that of free curcumin, exhibits better efficacy in reducing tumor incidence and multiplicity than free curcumin, thereby hampering development of B[a]P-induced lung adenocarcinomas in Swiss albino mice. Hence, our study underscores the supremacy of the formulation over free curcumin and establishes it as a potential chemopreventive and oral supplement against environmental carcinogenesis.

The expansion and stability of foams made from remelted aluminium alloy scrap has been studied. Foams made from scrap alloy contain oxide bi-films introduced from the swarf (machining chips and turnings) of LM26 alloy and these oxides act as stabilizing agents. The wettability of the oxides and hence the stabilisation is studied by varying the addition of Mg (0 to 2 wt.%) in the alloy. The viscosity of the melts with and without Mg addition is measured and correlated with foam expansion and stability. A detailed microstructural analysis of the base alloy and foam cell wall was conducted to obtain an understanding of the stabilisation behaviour of oxides.

Synthesis and evaluation of poly(ethylene glycol) grafted poly(O-benzyl ether) dendrimers for polymer assisted organic reaction is presented here. Initially a cross-linked polymer Polystyrene-Poly(ethyleneglycol)dimethacrylate-Vinylbenzylchloride (PS-PEGDMA-VBC) was synthesized by radical suspension polymerization. 1,3,5-tris(hydroxymethyl)benzene dendron was prepared by the reduction of trimesic acid using LiAlH 4 . Dendrimers were generated on 2 mol% cross-linked resin by repetitive Williamson etherification and thionyl chloride reactions. The dendrimer was cleanly and efficiently prepared up to third generations (G 3 ) and each stage of reaction was quantitatively and qualitatively analyzed. Poly(ethylene glycol) having different chain lengths (400 Da and 1500 Da) were grafted to G 3 generation and tested for various physico-chemical properties. The utility of supports were checked by synthesizing linear as well as disulfide bonded endothelin peptides in high yield and purity by standard Fmoc method.

Herein we report curcumin entrapped nanoparticles of PLGA–PEG copolymer which were conjugated with folic acid (PPF copolymer) for site specific targeting since many cancer cells exhibit external folic acid binding receptors. The PPF copolymer was synthesised by two steps using DCC/NHS chemistry and characterized by FT-IR and 1H-NMR techniques. The curcumin was encapsulated in PPF by single emulsion-solvent evaporation method. The nanoparticles were characterised by TEM and DLS for their size and morphology. The thermal properties were assessed by DSC data. In vitro release kinetics measurements of the drug from the nanoparticles showed a controlled release pattern over a period of time. The MTT assay depicted a high amount of cytotoxicity of PPF nanocurcumin in HeLa cells. Cellular uptake studies demonstrated the efficacy of surface engineering with folate over free nanoparticles. Furthermore, the biological evaluations, for example AO/EB staining, DAPI staining, and clonogenic assay of the nanoparticles confirm the efficacy and mechanism by which the cytotoxicity was induced.

Industrial research in the field of dry powder inhalation (DPI) technology is still confined to the micronization of active pharmaceutical ingredients (APIs). Earlier studies have identified triboelectric charge as the main reason for the reduced efficiency of most of the marketed formulations. The physical instability of the micronized product aggravates the situation. Direct conversion of an API into an inhalable dry crystal, without applying an attritional force, would be a solution for many issues such as loss of crystallinity or metal contamination of the final product. In this work, Isoniazid (INH) (an anti-TB drug) was converted to inhalable particles using cryo-crystallization under a partial anti-solvent environment. The crystals were dried using a lyophilization technique and furthermore, the powder was characterized. PXRD studies showed that a new polymorph was evolved by the proposed technique. Since lyophilization is a closed method, microbial contamination can also be avoided through this method. Accelerated stability studies at 40 °C with 75% relative humidity indicated that the newly formed crystals had similar stability to that of the raw material (the API).

Aluminium alloy foams are created by injecting air into liquid alloys containing non metallic particles. In addition to an alloy containing the usual SiC particles, other types of metal particle composites are studied, which are created by in situ reactions in the melts two fluoride salts react and form TiB2 particles, and Ca addition or addition of CuO and SiO2 gives rise to the formation of various oxides and spinel particles. Injecting air into the molten composites through two different steel cannulas leads to the formation of first bubbles and then foam. The entire process is monitored in situ by X ray radioscopy. The goal is not only to understand how and what kind of particles stabilise gas injected foams better, but also to reduce the fraction of added particles, which could improve mechanical properties, solve recycling issues and reduce production costs. All the observed composites are shown to have the potential to be processed to metallic foam. Melts containing TiB2 particles are found to perform as well as those containing SiC even at lower volume fractions. Oxidation of alloy melts promoted by Ca addition gives rise to melts that exhibit good foamability. Melts oxidised by CuO and SiO2 addition show partial stability. Mg is found to be a required alloying element to create stable foams. Smaller bubbles can be produced using smaller injector needle openings. By reducing bubble size and using new variants of in situ generated particles, more stable foams can be achieved with a lower number density of stabilising particles

PEG grafted (PEG400 and PEG1500), highly hydrophobic/hydrophilic balanced polymeric Schiff base dendron resins were synthesized by the reaction between diethylenetriamine and benzaldehyde molecules and characterized. The usefulness of the resins was demonstrated by synthesizing biologically significant linear as well as disulfide classes of endothelin peptides in high yields and purities.

Aluminium-based single films were pulled out of a melt using circular wire frames and characterised with respect to their stability under varied conditions. Pure Al, AlSi9 and AlSi9Mg0.6 alloys as well as particle reinforced composites based on the same alloys but adding different amounts of stabilising SiC or TiB2 particles were prepared. The velocity at which films were drawn was varied to investigate their solidification as well as their oxidation behaviour. In order to study the influence of the oxygen content of the foaming atmosphere a chamber was manufactured that allows for pulling single films under defined conditions. It was found that films without Mg were less stable than Mg-containing ones and even the addition of particles to such Mg-free alloys results in no improvement. In contrast, films made of AlSi9Mg0.6 were more stable and required only a small amount of oxygen (> 200 ppm O2), but in general some oxygen has always to be present to obtain a stable film. It was found that the more particles are contained in the composite and the slower the film gets pulled, the lower the required oxygen content is. © 2014 The Authors. Published by Elsevier Ltd. Peer-review under responsibility of Scientific Committee of North Carolina State University.

Complex liquid structures such as metallic foams were produced in a furnace that allowed in situ X-ray monitoring of the evolution of the structure and distribution of the liquid in the foam. The experiments were carried out during parabolic flights which provided varying levels of gravity. The evolution of the characteristic liquid fraction profiles due to gravity induced drainage was measured and analysed in terms of the foam drainage equation, obtaining viscosity and surface tension by fitting solutions of the equation to the experimental data. The surface tension of the melt in the foam was decreased up to 40%. Effective viscosities of up to 139 times the viscosity of a pure bulk melt were observed. These effects could be attributed to the smaller influence of solid particles dispersed in the melt and the larger influence of the complex foam structure. � 2014 the Partner Organisations.

Liquid metallic alloys with and without stabilizing particles such as TiB2 or SiC were processed to single films or artificial single Plateau borders to clarify the stabilization mechanisms of metallic foams based on the same melts. First, isolated single films were pulled out of a liquid metal by using circular wire frames of various sizes. Modified wire frame structures comprising double or quadruple parallel frames were then used to create artificial metallic Plateau borders. Drainage in single metallic films between two Plateau borders was studied by cutting films vertically and analysing their cross sections. Particle movement in liquid films was observed in-situ via synchrotron X-ray radioscopy. It was found that Mg-free liquid metallic alloys containing stabilising particles are less stable and rupture immediately because of unhindered drainage. In contrast, films made of AlSi9Mg0.6 alloy containing TiB2 or SiC are stable for long holding times. Our study shows that the complexity of drainage and evolution of Plateau borders in true metal foams can be studied by using a simple model system based on a single metallic film between two artificial Plateau borders.

Poly(N,N-bisethylamine) dendrimers with high content of poly(ethylene glycol) were synthesized on 3-(Acryloyloxy)-2-hydroxypropylmethacrylate-crosslinked polystyrene (PS-AHMA) resin and tested in various conditions of solid phase peptide synthesis. The dendritic templates were generated to the second generation on cross-linker active site of 3-(Acryloyloxy)-2-hydroxypropylmethacrylate (AHMA). First generation dendrimer was designed by series of four-stage reactions, such as Schiff base incorporation, acidolytic cleavage, diazotization and thionyl chloride treatment and same synthetic routes were followed for second generation also. Poly(ethylene glycol) (PEG1000) has been grafted to second-generation dendrimer and used to check various physico-chemical parameters in Fmoc/Boc peptide synthetic conditions. The utility of PEGylated dendrimer support was demonstrated by synthesizing biologically potent linear as well as disulfide-bonded peptide by Fmoc method.

Aluminum alloys made from machining chips that have been heat treated and re-melted, have been successfully foamed (after the addition of TiH2) using processes analogous to both the “Alporas” and “Formgrip” methods. The high oxygen contents associated with the swarf (0.11 wt% for the as-received material, increasing to >0.5 wt% after conditioning) results in large fractions of both clustered and dispersed oxide films in the melt. It is these films that enhance the “foamability” of this material. Through additional alloying with Mg and holding in the liquid state to allow reaction to take place, fragmentation and wetting of the oxides occurs and foams with low densities (

Poly(propyleneglycol)dimethacrylate cross-linked support using monomers Styrene and 4-chloromethyl styrene (PS-PPGDMA-VBC resin) was prepared by suspension polymerization method. Dendritic templates were synthesized from Schiff base and trimesic acid molecules and assembled independently on PS-PPGDMA-VBC support to the second generation. N,N-bischloro ethyl amine dendrimer was generated from Schiff base units and introduced to the chloromethyl groups uniquely through secondary amine. It was followed by acidolytic cleavage, diazotization and thionyl chloride reactions leading to first generation dendrimer. O-benzyl ether dendrimer was created using 1,3,5-tris(hydroxyl methyl)benzene unit which was produced by the LiAlH 4 reduction of carbonyl groups of trimesic acid molecule. The hydroxyl methyl groups formed were converted to chloro methyl groups by adding thionyl chloride that leads to first generation dendrimer. Similar synthetic routes were followed to produce second generation dendrimers too. Poly(ethylene glycol), M n ≈ 1500) has been grafted to chlorine termini of both dendrimers and used to check various physical and chemical properties of different peptide synthetic conditions. Reactions were qualitatively analyzed by FTIR, 13 C NMR, SEM and quantitatively analyzed by UV measurements and CHN analysis. Classically difficult ACP sequence was synthesized on both PEGylated dendrimer supports and compared to Tenta Gel. Biologically significant disulfide bonded endothelin class of peptides were also synthesized using novel supports using various literature reported methods.

G Deepa,1 Arun Kumar T Thulasidasan,2 Ruby John Anto,2 J Jisha Pillai,1 GS Vinod Kumar11Chemical Biology, 2Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, IndiaObjective: To investigate cross-linked hydrogels prepared via inverse emulsion polymerization to entrap poorly aqueous soluble drugs. Polyethylene glycol cross-linked acrylic polymers were synthesized and the loading and release of curcumin, a model hydrophobic drug, was investigated.Methods: Physicochemical characteristics of hydrogels were studied with 13C nuclear magnetic resonance, Fourier transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, differential scanning calorimetry, and swelling. Polymerization of the acrylic acid with cross-linked polyethylene glycol diacrylate was characterized with 13C nuclear magnetic resonance imaging and Fourier transform infrared spectroscopy.Results: The in vitro release rate of curcumin showed that there was a sustained release from the hydrogel with increased cross-linking; the release rate depended on the pH of the releasing medium. Intracellular and cytotoxicity studies were carried out in human cervical cancer cell lines.Conclusion: The results suggest cross-linked acrylic polymers can be used as efficient vectors for pH-sensitive, controlled delivery of hydrophobic drugs.Keywords: curcumin, cross-linked polyethylene glycol, polyacrylic acid, nanogel, cross-linking combinations, HeLa

Curcumin, a yellow pigment present in turmeric, possess potential anti-proliferative and anti-inflammatory activities but poor aqueous solubility limits its applications. In this study we report a novel comparative study of the formulation and characterization of curcumin nanoparticles (nanocurcumin) using two poly (lactide-co-glycolide) (PLGA) combinations, 50:50 and 75:25 having different lactide to glycolide ratios. Nanocurcumin 50:50 showed smaller size with higher encapsulation efficiency. Thermal evaluation suggested the presence of curcumin in molecular dispersion form which supported its sustained release up to a week where nanocurcumin 50:50 showed faster release. Cellular uptake studies in human epithelial cervical cancer cells (HeLa) exhibited enhanced intracellular fluorescence with nanocurcumin when compared to free curcumin, when both given in purely aqueous media. Antiproliferative studies using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, Annexin V/propidium iodide staining, poly (ADP-ribose) polymerase (PARP) cleavage and downregulation of clonogenic potential of HeLa cells proved the better antitumor activity of nanocurcumin 50:50 administered in aqueous media. Superior efficacy of nanocurcumin 50:50 in comparison to free curcumin was further demonstrated by electrophoretic mobility shift assay and immunocytochemical analysis. In conclusion, the enhanced aqueous solubility and higher anticancer efficacy of nanocurcumin administered in aqueous media clearly demonstrates its potential against cancer chemotherapy, with dependence on the combination of PLGA.

The present study describes the synthesis of different mole densities of poly(propylene glycol)dimethacrylate cross-linked resins using monomer units such as styrene and 4-chloromethyl styrene and its evaluation as an ideal support toward different stages of solid-phase peptide synthesis. Free radical generated aqueous suspension polymerization has been followed for polymerization and the formation of resin was characterized using infrared and carbon-13 spectroscopic techniques. Surface morphology of resin was examined by scanning electron microscopy. The polymerization reaction was investigated with respect to the effect of amount of cross-linking agent to verify the swelling, loading, and the mechanical stability of resin. Solvent imbibition abilities in commonly used solvents were measured and compared to commercially available Merrifield as well as reported styrene-acryloyloxyhydroxypropyl methacrylate-tripropyleneglycol diacrylate (SAT resins. The chemical inertness of the support was also checked with different reagents used for solid-phase peptide synthesis. The suitability of support was demonstrated by synthesizing biologically potent Endothelin class of linear peptides by Fmoc strategy and compared to SAT resin. The purities of synthetic peptides were analyzed by high-performance liquid chromatography and corresponding masses by matrix-assisted laser desorption/ionisation-time of flight analysis. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 98: 239–248, 2012.

The poor corneal residence time of pilocarpine, an alkaloid extracted from the leaves of the Jaborandi plant, limits its ocular application. The aim of this study was to develop, characterize, and evaluate the potential of pilocarpine entrapped by poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticle carriers for ocular drug delivery. Pilocarpine-loaded nanoparticles were prepared with a double-emulsion (water in oil in water) method and characterized with transmission electron microscopy and X-ray diffraction analysis. The nanoparticles exhibited an average size of 82.7 nm with an encapsulation efficiency of 57%. Stability studies showed the absence of agglomeration and constancy in the amount of drug entrapped; this indicated the solidity of these particles for long-term use. The in vitro release studies conducted in simulated tear fluid showed the sustained release of pilocarpine. In vivo evaluation of the nanoparticles was done in a rabbit model with a miosis assay and compared to an equal dose of commercially available eye drops of pilocarpine (Pilocar drops). The in vivo miosis studies showed that the duration of miotic response increased by 40% for the nanoparticles and produced an almost 68% increase in total miotic response when compared to the eye drops. In conclusion, this study clearly demonstrated the potential of pilocarpine-loaded PLGA nanoparticles for multiplying the therapeutic effect of ophthalmic drug delivery with enhanced bioavailability and pharmacological response. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

A novel foamable aluminum alloy has been developed. It contains sub-micron-sized MgAl2O4 (spinel) particles that are generated in situ by a reaction of SiO2 with a molten Al-Mg alloy. The study involves an optimization of parameters such as Mg concentration, SiO2 particles size, and reaction time and shows that a composite containing MgAl2O4 particles as chief reinforcement in the matrix leads to effective foaming. Composites containing large sized transition phases and particle agglomerates in the matrix yield poor foam structure. The best foamable composite obtained contained 3.4 vol. pct of ultrafine (80 nm to 1 μm) MgAl2O4 particles uniformly distributed in an Al-Si alloy matrix. The corresponding metal foam contained 75 pct porosity and exhibited a uniform distribution of cells.

Strontium-modied Al-15wt%Si casting alloys were investigated after 5 and 60 minutes of melt holding. The eutectic microstructures were studied using complementary methods at dierent length scales: focused ion beamenergy selective backscattered tomography, transmission electron microscopy and three-dimensional atom probe. Whereas the samples after 5 minutes of melt holding show that the structure of eutectic Si changes into a ne brous morphology, the increase of prolonged melt holding (60 minutes) leads to the loss of Sr within the alloy with an evolution of an unmodied eutectic microstructure displaying coarse interconnected Si plates. Strontium were found at the Al/Si eutectic interfaces on the side of the eutectic Al region, measured by three-dimensional atom probe. The new results obtained using three-dimensional atom probe shed light on the location of Sr within the Al-Si eutectic microstructure.

An investigation into the effect of ternary alloying element additions such as copper, magnesium, manganese, zinc, and nickel on pore formation in cast Al-12.6-wt pct Si eutectic alloy by employing a novel pore characterization technique is reported here. In this approach, the low-pressure testing method was combined with the metal foam manufacturing technique of intentionally adding TiH2, which enhances hydrogen pore formation and offers a method to distinguish the effect of individual alloying elements on hydrogen porosity formation.

The effect of TiAl3 particle size and distribution on their settling and dissolution behaviour in molten aluminium during grain refinement has been studied. For this purpose Al-5Ti master alloys containing blocky TiAl3 particles of different size and distribution are synthesised at reaction temperatures 750, 800 and 850 �C for 60 min and used for grain refinement. The extent of fading and the recovery due to stirring is calculated from the measured grain size and used to judge the dissolution and settling behaviour of TiAl3 in molten Al, which is greatly attributed to its size and distribution in Al-5Ti master alloy. Fine TiAl3 particle dissolve faster in the melt and cause fading. Larger size TiAl3 particles exist for longer time in molten Al and act as a nucleating site even when added in hypoperitectic concentration (0.05 wt% Ti). � 2010 Springer Science+Business Media, LLC.

Effective delivery of drugs to alveoli in a controlled manner using hydrophobic polymers as carriers has already been reported. Preclinical studies revealed that toxicity and hydrophobicity are related to each other in pulmonary delivery. Here, we are reporting a chemically modified dextran having amphiphilicity and cationicity achieved by controlled grafting of stearyl amine. Two proportions of lipopolymers were synthesized and physico-chemical characterization was carried out. In vivo evaluation of sub-acute toxicity of the synthesized lipopolymer in Sprague–Dawley rats was carried out for three months. This was followed by a histological evaluation of the sacrificed animal’s lung. Further, the synthesized lipopolymer was formulated with drug (Rifampicin) loaded inhalable microparticles through spray drying. The final drug formulation was tested for toxicity and proinflammatory responses in human cell lines. Dose deposition efficiency of the formulation was determined using Anderson Cascade Impactor.

Al-5Ti-0.8C and Al-5Ti-1.2C master alloys have been successfully prepared by reaction of K2TiF6 salt and graphite powder with molten Al. While the Al-5Ti-0.8C consists of some TiAl3 particles in addition to TiC particles in the Al matrix, the Al-5Ti-1.2C master alloy revealed the presence of only TiC particles. The grain refining efficiency of these two master alloys has been compared with that of the conventional Al-5Ti-1B master alloy on Al and Al-7Si alloy at different addition levels. Al-5Ti-1.2C master alloy was found to be the most efficient grain refiner for Al amongst the grain refiners studied. Even in case of Al-7Si alloy, the Al-5Ti-0.8C and Al-5Ti-1.2C master alloys performed better than conventional Al-5Ti-1B master alloy. However, the Al-5Ti-1.2C master alloy shows poor response to grain refinement in Al-7Si alloy at higher addition levels than the Al-5Ti-0.8C master alloy, indicating poisoning. ? 2005 Elsevier B.V. All rights reserved.

Crosslinked polystyrene ethylene glycol acrylate resin (CLPSER) was developed for the immobilization of the enzyme catalase by the introduction of a crosslinker, O,O′-bis(2-acrylamidopropyl) poly(ethylene glycol)1900, to styrene. The crosslinker was prepared by the treatment of acryloyl chloride with O,O′-bis(2-aminopropyl) poly(ethylene glycol)1900 in the presence of diisopropylethylamine. The resin was characterized with IR and 13C-NMR spectroscopy. The catalytic activity of the catalase-immobilized system of CLPSER was compared with divinylbenzene-crosslinked polystyrene, ethylene glycol dimethacrylate crosslinked polystyrene, and 1,4-butanediol dimethacrylate crosslinked polystyrene systems. Crosslink levels of 2, 8, and 20 mol % were evaluated. Among these crosslinked systems, the 2 mol % system was found to be most suitable to support catalytic activity. When a long flexible hydrophilic poly(ethylene glycol) crosslink, introduced between the polystyrene (PS) backbone and functional groups was used for immobilization, the extent of coupling and enzyme activity increased. Depending on the nature of the support, the catalytic activity of the system varied. The hydrophilic CLPSER support was most efficient for immobilization compared to the other PS-based supports. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 8–19, 2005

Metal complexation behavior of Schiff base function supported on 2 mol% DVB‐, EGDMA‐, BDDMA‐, HDODA‐, and TTEGDA‐crosslinked polystyrenes and the catalase‐like activity of the resulting polymer–metal complexes were followed. The polymeric ligands and metal complexes were characterized by IR, UV, EPR, and SEM analyses. The catalytic activities of these metal complexes were investigated in the decomposition of hydrogen peroxide as a model reaction. The Fe(II), Fe(III), Co(II), Ni(II), and Cu(II) complexations of the various crosslinked systems varied with the nature of the crosslinking in the polystyrene backbone. The metal uptake followed the order: Cu(II) > Co(II) > Ni(II) > Fe(III) > Fe(II). Among the various metal complexes, Co(II) and Cu(II) complexes are efficient for showing the catalase‐like activity. The metal ion complexation and catalytic activity decreased with increasing hydrophilicity of the crosslinking agent in the polymer support.

A high swelling resin, CLPSER has been developed and utilized for the solid phase synthesis of Pardaxin, which is an 18-residue peptide. The resin was characterized by gel phase (13)C NMR, IR and SEM. The utility of the new polymer support in polypeptide synthesis was further established by the comparative synthesis of pardaxin with commercially available Merrifield resin. The MALDI TOF MS, amino acid analysis and the HPLC revealed the superior quality of CLPSER.

Catalase-like activity of the metal complexes of various crosslinked polystyrene-supported Schiff bases were carried out and correlated with the nature and degree of crosslinking in the polymer support. Polystyrenes with 2–20 mol % ethyleneglycol dimethacrylate (EGDMA), 1,4-butanediol dimethacrylate (BDDMA) and 1,6-hexanediol diacrylate (HDODA) were used as polymer supports. functions of diethylenetriamine and salicylaldehyde were incorporated to the chloromethylpolystyrene by polymer analogous reactions and complexed with Fe(II), Fe(III), Co(II), Ni(II), and Cu(II) ions. The metal uptake decreased in the order: Cu(II) > Co(II) > Ni(II) > Fe(III) > Fe(II), and extent of metal uptake by the various crosslinked system varied with the nature and degree of the crosslinking agent. The polymeric ligands and the metal complexes were characterized by various analytical techniques. The catalytic activities of these metal complexes were investigated towards the decomposition reaction of hydrogen peroxide. Generally among the various metal complexes, the catalytic activities decreased in the order: Co(II) > Cu(II) > Ni(II) > Fe(III) ≅ Fe(II). With increasing rigidity of the crosslinking agent their catalytic activity also decreased. Of the various crosslinked systems, the catalytic activity decreased in the order: HDODA- > BDDMA- > EGDMA-crosslinked system. Also, the catalytic activity is higher for low crosslinked systems and decreased further with increasing degree of crosslinking. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 1271–1278, 2004

The encapsulation of 5-fluorouracil (5-FU) in hydrophobic polymeric materials is made feasible by a lipid-based prodrug approach. A lipid-5-FU conjugate of 5-FU with palmitic acid was synthesized in two-step process. A synthesized dipalmitoyl derivative (5-FUDIPAL) was characterized using Fourier transform infrared spectroscopy and (1)H-nuclear magnetic resonance. The 5-FUDIPAL was encapsulated in polyester-based polymers by the double emulsion-solvent evaporation method. The nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy and dynamic light scattering. The thermal stability was assessed by differential scanning calorimetry data. In vitro release kinetics measurements of the drug from nanoparticles showed the controlled release pattern over a period of time. Cytotoxicity measurements by MTT assay confirmed that dipalmitoyl derivative in nano formulation successfully inhibited the cell growth. Thus the combined physical and biological evaluation of the different polyester-based nanoparticle containing the modified drug showed a facile approach to delivering 5-FU to the tumour site with enhanced efficacy.