Genome mining, in silico validation and phase selection of a novel aldo-keto reductase from Candida glabratea for biotransformation

Previously, we published cloning, over-expression, characterization and subsequent exploitation of a carbonyl reductase (cr) gene, belonging to general family aldo-keto reductase from Candida glabrata CBS138 to convert keto ester (COBE) to a chiral alcohol (ethyl-4-chloro-3-hydroxybutanoate or CHBE). Exploiting global transcription factor CRP, rDNA and transporter engineering, we have improved batch production of CHBE by trinomial bioengineering. Herein, we present the exploration of cr gene in Candida glabrata CBS138 through genome miningapproach, in silico validation of its activity and selection of its biocatalytic phase.For exploration of the gene under investigation, three template genes were chosen namelySaccharomyces cerevisae YDR541c, YGL157w and YOL151w. The CR showed significant homology match, overlapping of substrate binding site and NADPH binding sitewith the template proteins. The binding affinity of COBE towards CR (−4.6 Kcal/ mol) was found higher than that of the template proteins (−3.5 to −4.5 Kcal/ mol). Biphasic biocatalysis with cofactor regeneration improved product titer 4∼5 times better than monophasic biotransformation. Currently we are working on DNA Shuffling as a next level of strain engineering and we demonstrate this approach herein as a future strategy of biochemical engineering

Theranostics Application of Graphene-Based Materials in Cancer Imaging, Targeting and Treatment

Recent advancements in graphene-based nanomaterials provide the opportunity that compliments the limitations of conventional drug delivery systems (DDSs) through simultaneous targeting of the anticancer drug to the cancer cell by reducing the side effects of other administration routes. Graphene with its extraordinary electronic properties like larger surface area, possibilities of surface modification, can efficiently target the tumor cell. At the same time, nanocarriers have the advantages of immune clearance adulteration of physicochemical properties of anticancer drug. The DDSs can be made by biodegradable nanocarriers such as proteins, peptides, biocompatible polymers, antibodies, polymer-drug conjugates, etc. Graphene-supported DDSs in cancer therapy also supports the co-delivery of therapeutic agents, antioxidants, SiRNA, shRNA, etc. as the co-delivery approach, which provide additive or synergistic therapeutic efficacy and can reduce toxic effects

The application of graphene oxide in drug delivery

Introduction: As a shining star in material science, graphene oxide (GO) and its derivatives possess potential applications in a variety of areas. Among them, the application of GO to drug delivery has attracted ever-increasing interest in the past few years. Areas covered: In this article, the authors summarize the latest progress of utilizing GO in the field of drug delivery. In particular, the functionalization of GO, cytotoxicity of GO and its derivatives, in vitro and in vivo drug delivery and the comparison with carbon nanotube-based delivery systems are discussed. Future perspectives and possible challenges in this emerging field are briefly described. Expert opinion: GO and its derivatives are highly attractive for the application to drug delivery due to their exceptional physiochemical properties and unique planar structure in spite of some existing challenges, such as the reproducibly smart functionalization of GO and the investigation of its long-term toxicology

Bio-Vitrimers for Sustainable Circular Bio-Economy

The aim to achieve sustainable development goals (SDG) and cut CO2-emission is forcing researchers to develop bio-based materials over conventional polymers. Since most of the established bio-based polymeric materials demonstrate prominent sustainability, however, performance, cost, and durability limit their utilization in real-time applications. Additionally, a sustainable circular bioeconomy (CE) ensures SDGs deliver material production, where it ceases the linear approach from production to waste. Simultaneously, sustainable circular bio-economy promoted materials should exhibit the prominent properties to involve and substitute conventional materials. These interceptions can be resolved through state-of-the-art bio-vitrimeric materials that display durability/mechanical properties such as thermosets and processability/malleability such as thermoplastics. This article emphasizes the current need for vitrimers based on bio-derived chemicals; as well as to summarize the developed bio-based vitrimers (including reprocessing, recycling and self-healing properties) and their requirements for a sustainable circular economy in future prospects

Preparation of nanoparticles of poorly water-soluble antioxidant curcumin by antisolvent precipitation methods

The objective of this study was to enhance the solubility and dissolution rate of a poorly water-soluble antioxidant, curcumin, by fabricating its nanoparticles with two methods: antisolvent precipitation with a syringe pump (APSP) and evaporative precipitation of nanosuspension (EPN). For APSP, process parameters like flow rate, stirring speed, solvent to antisolvent (SAS) ratio, and drug concentration were investigated to obtain the smallest particle size. For EPN, factors like drug concentration and the SAS ratio were examined. The effects of these process parameters on the supersaturation, nucleation, and growth rate were studied and optimized to obtain the smallest particle size of curcumin by both the methods. The average particle size of the original drug was about 10–12 μm and it was decreased to a mean diameter of 330 nm for the APSP method and to 150 nm for the EPN method. Overall, decreasing the drug concentration or increasing the flow rate, stirring rate, and antisolvent amount resulted in smaller particle sizes. Differential scanning calorimetry studies suggested lower crystallinity of curcumin particles fabricated. The solubility and dissolution rates of the prepared curcumin particles were significantly higher than those the original curcumin. The antioxidant activity, studied by the DPPH free radical-scavenging assay, was greater for the curcumin nanoparticles than the original curcumin. This study demonstrated that both the methods can successfully prepare curcumin into submicro to nanoparticles. However, drug particles prepared by EPN were smaller than those by APSP and hence, showed the slightly better solubility, dissolution rate, and antioxidant activity than the latte

Ternary dispersions to enhance solubility of poorly water soluble antioxidants

The main aim of this study was to enhance the solubility and dissolution rate of the two poorly water-soluble antioxidants, curcumin (CUR) and hesperetin (HSP). Binary dispersions of the two drugs in the polymer, polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG) matrix were prepared. A surfactant (Pluronic F127 or Tween 80) was also combined with the polymer to develop ternary solid dispersions to further improve the dissolution properties of CUR and HSP. The FTIR study suggested hydrogen bonding between PVP and the drugs and minor intermolecular interactions between PEG and drugs. PVP showed better amorphizing nature than PEG as inferred from the DSC and XRD study. The surfactants added in the ternary dispersions further enhanced the intermolecular interaction of the polymers with the drugs. The 2D micro-Raman spectroscopic mapping showed that after adding the surfactants in the ternary dispersions, CUR and HSP were more uniformly distributed in the PEG matrix. The solubility and dissolution rates of CUR and HSP were increased by dispersing them in the polymer matrix and the increase was dramatic when the surfactant was added to the dispersion system. The intermolecular interactions between drug and carriers led to better dispersion of drug in the polymer matrix and reduction in the size of drug particles; increase in the amorphous nature, decrease in surface tension and increase in the wettability which resulted in enhanced solubility and dissolution of the ternary dispersions. The ternary dispersions also presented better long term stability in terms of the amorphous nature and the dissolution properties

Thermal kinetics of montmorillonite nanoclay/maleic anhydride-modified polypropylene nanocomposites

Thermal kinetics of montmorillonite nanoclay (MMT)/maleic anhydride-modified polypropylene (MAH-PP) composites (PPCNs) is reported here in terms of thermal stability, decomposition, and crystallization kinetics. The effects of MMT nanoclay on the thermal stability of PP in MMT/MAH-PP composites have been examined at different heating rates by means of thermogravimetric (TG) analysis. Based on the TG results, the Ozawa method was applied to determine the activation energies of decomposition for MMT/MAH-PP composites and the results were then verified by the Kissinger method. It was found that the thermal stability of PP was significantly improved in the presence of MMT nanoclay. Differential scanning calorimetry (DSC) was used to study the melting and crystallization behaviors of MMT/MAH-PP composites under various thermal conditions. Using the data from DSC, the Kissinger method was applied to estimate the activation energies of PPCNs which were required during their non-isothermal crystallization. The activation energies of crystallization showed that MMT nanoclay served as a nucleating agent in the non-isothermal crystallization of PP in the PPCNs and as a result, the crystallinity of PP was greatly enhanced. Therefore, the presence of MMT nanoclay in MMT/MAH-PP composites effectively modified the thermal kinetics of PP

Fabrication of quercetin nanoparticles by anti-solvent precipitation method for enhanced dissolution

The aim of this study was to enhance the dissolution rate of a poorly water-soluble drug quercetin by fabricating its nanoparticles with anti-solvent precipitation using the syringe pump and to investigate the effect of drug concentration, solvent to anti-solvent (S/AS) ratio, stirring speed and flow rate on the particle size. Characterization of the original quercetin powder and nanoparticles made by syringe pump was carried out by the scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and dissolution tester. The results indicated that decreasing the drug concentration, increasing the stirring speed, flow rate and the S/AS volume ratio favoured the reduction in the particle diameter to ∼ 170 nm. Percent dissolution efficiency (%DE); relative dissolution (RD); mean dissolution time (MDT); difference factor (f1) and similarity factor (f2) were calculated for the statistical analysis. The dissolution of the drug nanoparticles was significantly higher compared with the pure drug in simulated intestinal fluid (SIF, pH 6.8)

Development and Characterization of Biocompatible Fullerene [C60]/Amphiphilic Block Copolymer Nanocomposite

We report a supramolecular process for the synthesis of well-defined fullerene (C60)/polymer colloid nanocomposites in an aqueous solution via complex formation. A biocompatible triblock poly(4-vinylpyridine)-b-polyethylene-b-poly(4-vinylpyridine), P4VP8-b-PEO105-b-P4VP8, was synthesized by atom transfer radical polymerization. The block copolymer formed complexes with C60 in toluene and resulted in fullerene assembly in cluster form. Nanocomposite dispersion in an aqueous solution could be obtained using an aged solution of the polymer/C60/toluene solution by a solvent evaporation technique. The UV-Vis and FTIR spectroscopy confirmed the complex formation of fullerene with the polymer which plays a significant role in controlling the PDI and size of polymer/C60 micelles in the toluene solution. The particle size and morphology of P4VP8-b-PEO105-b-P4VP8 and P4VP8-b-PEO105-b-P4VP8/C60 mixture were studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In a cytotoxicity test, both pure polymer and the resulting polymer/C60 composite in water showed more than 90% cell viability at 1 mg/mL concentration.NRF (Natl Research Foundation, S’pore)Published versio

Current Advances in the Carbon Nanotube/Thermotropic Main-Chain Liquid Crystalline Polymer Nanocomposites and Their Blends

Because of their extraordinary properties, such as high thermal stability, flame retardant, high chemical resistance and high mechanical strength, thermotropic liquid crystalline polymers (TLCPs) have recently gained more attention while being useful for many applications which require chemical inertness and high strength. Due to the recent advance in nanotechnology, TLCPs are usually compounded with nanoparticles to form particulate composites to enhance their properties, such as barrier properties, electrical properties, mechanical properties and thermal properties. Carbon-based nanofillers such as carbon nanotube (CNT), graphene and graphene oxide are the most common fillers used for the TLCP matrices. In this review, we focus on recent advances in thermotropic main-chain liquid crystalline polymer nanocomposites incorporated with CNTs. However, the biggest challenges in the preparation of CNT/TLCP nanocomposites have been shown to be inherent in the dispersion of CNTs into the TLCP matrix, the alignment and control of CNTs in the TLCP matrix and the load-transfer between the TLCP matrix and CNTs. As a result, this paper reviews recent advances in CNT/TLCP nanocomposites through enhanced dispersion of CNTs in TLCPs as well as their improved interfacial adhesion with the TLCP matrices. Case studies on the important role of chemically modified CNTs in the TLCP/thermoplastic polymer blends are also included