Bio-Based Alternatives to Phenol and Formaldehyde for the Production of Resins.

Phenol-formaldehyde (PF) resin continues to dominate the resin industry more than 100 years after its first synthesis. Its versatile properties such as thermal stability, chemical resistance, fire resistance, and dimensional stability make it a suitable material for a wide range of applications. PF resins have been used in the wood industry as adhesives, in paints and coatings, and in the aerospace, construction, and building industries as composites and foams. Currently, petroleum is the key source of raw materials used in manufacturing PF resin. However, increasing environmental pollution and fossil fuel depletion have driven industries to seek sustainable alternatives to petroleum based raw materials. Over the past decade, researchers have replaced phenol and formaldehyde with sustainable materials such as lignin, tannin, cardanol, hydroxymethylfurfural, and glyoxal to produce bio-based PF resin. Several synthesis modifications are currently under investigation towards improving the properties of bio-based phenolic resin. This review discusses recent developments in the synthesis of PF resins, particularly those created from sustainable raw material substitutes, and modifications applied to the synthetic route in order to improve the mechanical properties.

Polyelectrolyte complex nanoparticles from cationised gelatin and sodium alginate for curcumin delivery.

Self assembled hybrid polyelectrolyte complex (PEC) nanoparticles are prepared from cationically modified gelatin and sodium alginate (Alg) by electrostatic complexation between the polymers. Cationised gelatin (CG) is prepared by the reaction of gelatin with ethylenediamine. Structural changes in gelatin, after modification with ethylenediamine are investigated by XRD and (1)H NMR spectroscopy. Hybrid polyelectrolyte nanoparticles, labeled CG/Alg, are prepared by simple mixing of CG and Alg. CG/Alg complex shows spherical morphology as confirmed by scanning electron microscopy. These polyelectrolyte complex nanoparticles can be used for the encapsulation and delivery of natural antioxidant curcumin to carcinoma cells. CG/Alg nanoparticles show curcumin encapsulation efficiency of 69% and exhibit sustained release of curcumin in vitro. Anticancer activity of curcumin loaded CG/Alg nanoparticles towards MCF-7 cells is disclosed by MTT assay. Intracellular uptake of the drug encapsulated nanoparticles is confirmed by fluorescent imaging.

Curcumin loaded gum arabic aldehyde-gelatin nanogels for breast cancer therapy.

Curcumin, a widely studied hydrophobic polyphenol with anticancer potential is loaded in gum arabic aldehyde-gelatin (GA Ald-Gel) nanogels to improve its bioavailability and therapeutic efficacy towards cancer cells. Physicochemical properties of the curcumin loaded GA Ald-Gel nanogels are investigated by different techniques including dynamic light scattering (DLS), NMR spectroscopy and scanning electron microscopy (SEM). These nanogels exhibit hydrodynamic diameter of 452±8nm with a zeta potential of -27mV. The nanogels possess an encapsulation efficiency of 65±3%. Potential of the nanogels for controlled release of curcumin is illustrated by in vitro drug release studies. Hemocompatibility and cytocompatibility of the drug loaded nanogels are evaluated. In vitro cytotoxicity of the bare and curcumin loaded nanogels are analyzed by MTT assay towards MCF-7 cells. The results manifest that curcumin loaded nanogels induce toxicity in MCF-7 cells. Confocal laser scanning microscopy (CLSM) studies indicate in vitro cellular uptake of the nanogels in MCF-7 cells. All these results prove the suitability of the curcumin loaded GA Ald-Gel nanogels for cancer therapy.

Galactosylated alginate-curcumin micelles for enhanced delivery of curcumin to hepatocytes.

Galactosylated alginate-curcumin conjugate (LANH2-Alg Ald-Cur) is synthesized for targeted delivery of curcumin to hepatocytes exploiting asialoglycoprotein receptor (ASGPR) on hepatocytes. The synthetic procedure includes oxidation of alginate (Alg), modification of lactobionic acid (LA), grafting of targeting group (modified lactobinic acid, LANH2) and conjugation of curcumin to alginate. Alginate-curcumin conjugate (Alg-Cur) without targeting group is also prepared for the comparison of properties. LANH2-Alg Ald-Cur self assembles to micelle with diameter of 235 ± 5 nm and zeta potential of -29 mV in water. Cytotoxicity analysis demonstrates enhanced toxicity of LANH2-Alg Ald-Cur over Alg-Cur on HepG2 cells. Cellular uptake studies confirm that LANH2-Alg Ald-Cur can selectively recognize HepG2 cells and shows higher internalization than Alg-Cur conjugate. Results indicate that LANH2-Alg Ald-Cur conjugate micelles are suitable candidates for targeted delivery of curcumin to HepG2 cells.

Microgravity as a means to incorporate HepG2 aggregates in polysaccharide-protein hybrid scaffold.

Tissue culture under microgravity provides a venue which promotes cell-cell association while avoiding the detrimental effects of high shear stress. Hepatocytes cultured on carriers or entrapped within matrices under simulated microgravity conditions showed improved cell function and proliferation. In the present study, a new approach was adopted where a non-cell adherent scaffold was incorporated with hepatospheroids (HepG2) under microgravity. Gum arabic (GA) was cross-linked with gelatin (GA-Gel) and collagen (GA-Col) to prepare non-cell adherent scaffolds. Microgravity experiments with GA-Gel and GA-Col indicated that GA-Col is a better substrate compared to GA-Gel. Microgravity experiments of GA-Col scaffolds with HepG2 cells confirmed that the non-adherent surface with porous architecture can incorporate hepatocyte spheroids and maintain liver specific functions. Albumin and urea synthesis of hepatocytes was sustained up to 6 days under microgravity conditions in the presence of GA-Col scaffold. This new approach of using non-cell adherent matrix and microgravity environment for developing biological substitutes will be beneficial in tissue engineering, bioartificial liver devices and in vitro safety assessment of drugs.

Gum arabic-curcumin conjugate micelles with enhanced loading for curcumin delivery to hepatocarcinoma cells.

Curcumin is conjugated to gum arabic, a highly water soluble polysaccharide to enhance the solubility and stability of curcumin. Conjugation of curcumin to gum arabic is confirmed by (1)H NMR, fluorescence and UV spectroscopy studies. The conjugate self assembles to spherical nano-micelles (270 ± 5 nm) spontaneously, when dispersed in aqueous medium. Spherical morphology of the self assembled conjugate is evidenced by field emission scanning electron microscopy and transmission electron microscopy. The self assembly of the amphiphilic conjugate into micelle in aqueous medium significantly enhances the solubility (900 fold of that of free curcumin) and stability of curcumin in physiological pH. The anticancer activity of the conjugate micelles is found to be higher in human hepatocellular carcinoma (HepG2) cells than in human breast carcinoma (MCF-7) cells. The conjugate exhibits enhanced accumulation and toxicity in HepG2 cells due to the targeting efficiency of the galactose groups present in gum arabic.

Galactosylated pullulan-curcumin conjugate micelles for site specific anticancer activity to hepatocarcinoma cells.

Galactosylated pullulan-curcumin conjugate (LANH2-Pu Ald-Cur SA) is developed for target specific delivery of curcumin to hepatocarcinoma cells by five step synthetic strategy, which includes oxidation of pullulan (Pu Ald), introduction of amino group to the targeting ligand (LANH2), grafting of the LANH2 to Pu Ald, modification of curcumin (Cur SA) and conjugation of Cur SA to pullulan. Nongalactosylated pullulan-curcumin conjugate (Pu-Cur SA) is also prepared to compare the enhancement in cytotoxicity offered by the targeting group. Both LANH2-Pu Ald-Cur SA and Pu-Cur SA conjugates could self assemble to micelle in water with hydrodynamic diameters of 355±9nm and 363±10nm, respectively. Both conjugates show spherical morphology and enhance stability of curcumin in physiological pH. Compared to Pu-Cur SA, LANH2-Pu Ald-Cur SA exhibits higher toxicity and internalization towards HepG2 cells. This indicates the enhanced uptake of LANH2-Pu Ald-Cur SA conjugate via ASGPR (asialoglycoprotein receptor) mediated endocytosis into HepG2 cells.

Preparation and characterisation of gelatin-gum arabic aldehyde nanogels via inverse miniemulsion technique.

Gelatin-gum arabic aldehyde nanogels designed by a nanoreactor concept using inverse miniemulsion technique were reported. Stable separate miniemulsions were prepared from gelatin (Gel) and gum arabic aldehyde (GAA). These emulsions were intermixed under sonication to obtain cross-linked nanogels. During fusion, cross-linking occurred between aldehyde groups of GAA and amino groups of gelatin. The concentration of the surfactant and weight fraction of water in the inverse miniemulsion was optimised so as to yield nanogels with controlled particle size. Properties of the nanogels were studied by FT-IR spectroscopy, particle size analysis and XRD. Surface morphology of the nanogels was established by Scanning Electron Microscopy (SEM). SEM and particle size analysis confirmed that nanogels possess spherical morphology with an average diameter of 151 ± 6 nm. Hemolysis property of the nanogels was examined and the results indicated that the nanogels were hemocompatible. The in vitro cytotoxicity of the nanogels towards MCF-7 cells was evaluated by MTT assay and the nanogels showed nontoxic behaviour towards the cells. All these studies confirm that these nanogels are potential candidates in applications such as drug and gene delivery.

Nanogels based on alginic aldehyde and gelatin by inverse miniemulsion technique: synthesis and characterization.

Nanogels were developed from alginic aldehyde and gelatin by an inverse miniemulsion technique. Stable inverse miniemulsions were prepared by sonication of noncontinuous aqueous phase (mixture of alginic aldehyde and gelatin) in a continuous organic phase (Span 20 dissolved in cyclohexane). Cross-linking occurred between alginic aldehyde (AA) and gelatin (gel) in the presence of borax by Schiff's base reaction during the formation of inverse miniemulsion. The effects of surfactant (Span 20) concentration, volume of the aqueous phase and AA/gel weight ratio on the size of the alginic aldehyde-gelatin (AA-gel) nanoparticles were studied. Nanogels were characterized by DLS, FT-IR spectroscopy, TGA, SEM and TEM. DLS, TEM and SEM studies demonstrated nanosize and spherical morphology of the nanogels. Hemocompatibility and in vitro cytocompatibility analyses of the nanogels proved their nontoxicity. The results indicated the potential of the present nanogel system as a candidate for drug- and gene-delivery applications.

A non-adhesive hybrid scaffold from gelatin and gum Arabic as packed bed matrix for hepatocyte perfusion culture.

Development of liver support systems has become one of the most investigated areas for the last 50 years because of the shortage of donor organs for orthotopic liver transplantations. Bioartificial liver (BAL) device is one of the alternatives for liver failure which provides a curing method and support patients to recover from certain liver failure diseases. The biological compartment of BAL is called the bioreactor where functionally active hepatocytes are maintained to support the liver specific functions. We have developed a packed bed bioreactor with a cytocompatible, polysaccharide-protein hybrid scaffold. The scaffold prepared from gelatin and gum Arabic acts as a packed bed matrix for hepatocyte culture. Quantitative evaluation of the hepatocytes cultured using packed bed bioreactor demonstrated that cells maintained liver specific functions like albumin and urea synthesis for seven days. These results indicated that the system can be scaled up to form the biological component of a bioartificial liver.

Modified gum arabic cross-linked gelatin scaffold for biomedical applications.

The present work deals with development of modified gum arabic cross-linked gelatin scaffold for cell culture. A new biocompatible scaffold was developed by cross-linking gelatin (Gel) with gum arabic, a polysaccharide. Gum arabic was subjected to periodate oxidation to obtain gum arabic aldehyde (GAA). GAA was reacted with gelatin under appropriate pH to prepare the cross-linked hydrogel. Cross-linking occurred due to Schiff's base reaction between aldehyde groups of oxidized gum arabic and amino groups of gelatin. The scaffold prepared from the hydrogel was characterized by swelling properties, degree of cross-linking, in vitro degradation and scanning electron microscopy (SEM). Cytocompatibility evaluation using L-929 and HepG2 cells confirmed non-cytotoxic and non-adherent nature of the scaffold. These properties are essential for generating multicellular spheroids and hence the scaffold is proposed to be a suitable candidate for spheroid cell culture.