[Thesis]: Green processes applied to nanoparticle technology: synthesis and formulation by Víctor Martín Velasco

Victor Martin Thesis

Dr. Víctor Martín Velasco defended his thesis on Tuesday 4th October 2016 at the University of Valladolid.

Nowadays, nanoparticle technology is investigated for being applied in a lot of fields, for example, in catalysis, materials, electronics and biomedicine, one of the most promising. This versatility is because of their properties associated to their size and morphology, such as surface absorption plasmon effect, specific area, reduction of melting point, reduction of superconductivity transition temperature, and increment of metal magnetic force. In order to achieve the desired properties, several synthesis methods have been developed, top down methods that involves a chemical or mechanical size reduction, and bottom up methods in which the particle grows from smaller entities. The main disadvantage of these methods is the use of organic toxic solvents and extreme operation conditions.

Novel processes must be environmental sustainable for their application in the real world, because of the growing concern about the planet damage. Green chemistry and engineering provides all the necessary tools to achieve the design of new processes or the modification of existing processes to accomplish this important target. Novel processes must decrease or eliminate wastes production, generate nontoxic product wherever possible and eliminate or replace solvents by benign solvents as supercritical fluids, ionic liquids, water or ethanol. Moreover the processes must be energetically efficient, avoid separation steps, use catalysts when it is possible to increase the efficiency and use renewable feedstocks.

The aim of this thesis is the study of some processes related to nanoparticle technology with green chemistry tools. In chapter 1, metal nanoparticles have been synthetized by bioreduction with grape pomace extract. This process uses water as solvent, natural nontoxic reagents, near ambient conditions and renewable feedstocks instead of toxic compounds, high pressure/temperature conditions and high costs, that the traditional process imply. Chapter 2 deals with nanoparticle formulation, a lipid is loaded with metal nanoparticles by PGSS®, and this process uses supercritical carbon dioxide, being a green option. Also, the process is fast and the solvent is eliminated by decompression, avoiding separation steps. Traditional method uses organic toxic compounds and needs solvent separation. Finally in chapter 3 and 4, a nanoparticle coating process has been developed by supercritical anti-solvent process in a fluidized bed. The solvents used are supercritical carbon dioxide and ethanol, both safe substances, reducing operation times and eliminating separation steps.

In chapter 1, metal copper nanoparticles have been produced by bioreduction method. This method consists on reducing metal ions in solution with compounds, produced by plant cells in their metabolism.

Figure 1: Copper synthesis reaction.
Figure 1: Copper synthesis reaction.

Usually plant extracts, which have all necessary compounds to achieve the reduction and stabilize the particle size, are used in instead of whole cells. It has been demonstrated that extract phenolic acids act as reducing agents while flavonols are capping agents, their concentration determines the particle size.  In this work, grape pomace extract, a waste of wine industry (figure 1), has been used, and their effect at different temperatures (30-55-80ºC), operation time (1-2-3 hours) and ratio (0.01- 0.05 – 0.1 g GAE/g Cu ion) studied, being temperature and time are the most influential variables. High temperatures increases the process yield but produce a fast consumption and/or degradation of capping agents, increasing the particle size to micrometric range. It is necessary a good selection of conditions to obtain particles in the nanometric range with the maximum possible yield.

Also, the growth process has been studied with and without capping agents in order to observe the effect (figure 2), and changing temperature and ratio conditions. In this case, two phases can be observed, in the first the size is constant over time, and in the second the capping effect finishes and the size increases rapidly due to a drop in capping agent concentration.

Figure 2: Particle size variation over during the reaction
Figure 2: Particle size variation over during the reaction

Finally, metal copper nanoparticle composition and morphology have been determined by XRD, TEM (figure 3) and EDS. The results show that copper particles have been obtained with a spherical morphology.

Figure 3: TEM image of the copper nanoparticles.
Figure 3: TEM image of the copper nanoparticles.

Some authors have demonstrated that copper nanoparticles have anti-cancer properties, owing to their toxicity and the looked-for application, it is necessary to formulate them. Therefore, in chapter 2, copper nanoparticles have been formulated with a lipid by PGSS®, a technic that uses supercritical carbon dioxide as solute, which is a clean substance recognized by green chemistry science, avoiding the use of organic solvent and several separation steps. The objective of this chapter is to study the PGSS process main operational variables (pre-expansion temperature (60-80ºC) and pressure (100-150 bar), water content (0-40% w/w) and copper load (0.5-5% w/w), in order to encapsulate copper nanoparticles in lipid microparticles.

The main important operating variable was the relationship between the amount of carbon dioxide and lipid, the process is badly affected at higher ratios. On the other hand, temperature and pressure in the studied range have not any critical effect in the process yield and in the final product particle size. Process yield presents a minimum when copper amount is increased due to stirring in pre-expansion chamber, but the particle size is barely affected.

This process allows incorporating copper in aqueous solution instead of copper in solid form. The effect of water depends on copper concentration. At higher concentration (5% w/w) the process yield do not change while particle size decreases, on the contrary, at low concentration (0.2% w/w) process yield remains constant until reach a concentration of water (20% w/w) where process yield decreases and particle size is increased.

Regarding the dispersion of copper metal in the lipid microparticles, the lower content of copper, the better dispersion is achieved due to the absence of copper agglomerates which is presented at high copper nanoparticle concentrations (5%w/w). Water have a positive effect on dispersion even though agglomeration is not avoided.

Figure 4: Copper dispersion in the lipid matrix
Figure 4: Copper dispersion in the lipid matrix

In chapter 3 and 4, a green coating process of inorganic nanoparticle agglomerates have been developed and their parameters studied. This process combines nanoparticle fluidization with supercritical carbon dioxide and anti-solvent process (SAS). This study has been carried out in two steps:

In chapter 3, fluidization of nanoparticles with supercritical carbon dioxide, as alternative to enhance fluidization quality, has been investigated by means of the determination of minimum fluidization velocity and its variation with supercritical fluid density and particle nature (primary size, bulk density…).

Nanoparticles belong to group C in Geldart classification, these particles are characterized by a high cohesion tendency, which causes problems in the fluidized bed, such as preferential paths, in addition, particles forms agglomerates and their size augments. Agglomeration takes place owing to cohesive forces, as London Van der Waals attractive forces, which depends on particle size. In order to solve this problem some technics such as vibrations, ultrasounds or electromagnetic fields, have been proposed. As an alternative, in this work, SFC has been used as fluidizing media due to the good results that it provided for microparticles fluidization.

 In this work, titanium oxide, magnetite and aluminum oxide nanoparticles have been considered. Minimum fluidization velocity varies with fluid density (figure 5), at high densities (above 500 kg/m3) the velocity is between 0.020 and 0.060 cm/s while at densities below 500 kg/m3 reach values up to 0.180 cm/s. Also, at high densities the same behavior have been observed for all nanoparticles but at low densities each particle has a different tendency related with primary particle size. Particles with lower primary particle size form bigger agglomerates and then, it is necessary a bigger velocity to fluidize them.

Figure 5: Minimum fluidization velocity variation with fluid density
Figure 5: Minimum fluidization velocity variation with fluid density

Titanium dioxide has been chosen as nanoparticle model and it has been coated with a polymer (Pluronic F-127) in chapter 4. An ethanolic solution of this polymer is pumped to fluidization chamber, supercritical carbon dioxide dissolves ethanol and polymer crystalizes on nanoparticle agglomerates. The main factors, that affect the process, have been studied: the ratio between the velocity of carbon dioxide through the bed and the minimum fluidization velocity (umf), with values from 1.5 to 2.5 times the umf; the density of carbon dioxide, varying from 640 kg/m3 to 735 kg/m3 approximately; the flow rate of solution, within an interval between 0.5-2 mL/min; the concentration of the solution, from 0.030 mg/mL to 0.090 mg/mL and the mass ratio polymer-particle, 0.45-1.8 g/g.

Figure 6: Coating process diagram.
Figure 6: Coating process diagram.

The most critical variables are solution flow rate and solution concentrations. These parameter can change process yield from 30% to 95% being the best option to work at low flows and concentrations. Polymer-particle mass ratio affects drastically the final coated particle size varying from 0.6 to 3.0 µm.

Final product has been analyzed by fluorescence microscopy and Fourier Transform Infrared Spectroscopy (FT-IR). These tests show that the polymer is present over the whole agglomerate. Coated particle bulk density has been measured in order to check the process, which increases linearly with the polymer-particle ratio, enhancing the manipulation of particles.

Figure 7: Fluorescence microscopy of titanium dioxide coated agglomerates
Figure 7: Fluorescence microscopy of titanium dioxide coated agglomerates

Thesis supervisors

  • Soraya Rodriguez Rojo
  • María José Cocero Alonso

Members of the Committee

  • Dr. Elisabeth Badens, Aix-Marseille Université
  • Dr. Angel Martín Martínez, Universidad de Valladolid
  • Dr. Miguel Menéndez Sastre, Universidad de Zaragoza
  • Dr. Maria Luz Rodríguez Méndez, Universidad de Valladolid
  • Dr. Ana Vital Morgado Marques Nunes, Universidade Nova de Lisboa

 

 

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