**5. Functionalization of nanoparticles in scCO2**

The modification of nanoparticle surfaces, either in solutions or as layers deposited on various surfaces, is a key issue in many processes to fabricate functional materials, in many applications. Commonly used methods for the modification of nanoparticles such as quantum dots, graphene, metallic nanoparticles, etc. are based on solution processing involving organic solvents, which makes the whole process very difficult to implement as eco-friendly technology. For biomedical applications in particular, the proper functionalization of the surfaces in synthesis that involve green solvents is particularly encouraged. Industrial or large-scale processes for the modification of surfaces by vapor-related physical methods suffer from huge limitations due to the high-cost and energy-consuming devices. On the other hand, liquid-related chemical methods have an additional drawback: the solvent removal after the reaction is completed on the targeted surface. Due to the variety of roles that can be attributed to carbon dioxide, i.e., solvent, antisolvent, reaction medium, respectively, unique flexibility for surface engineering is obtained using scCO2.

A variation of RESS method can be applied for coating processes, with the condition that coating material dissolves in scCO2. The solution is introduced via a nozzle in another chamber that contains the solid support to be functionalized. During the rapid depressurization, the density of CO2 changes significantly, and consequently a supersaturation followed by precipitation of the material forming a coating occurs. For example, superhydrophobic coatings on paper were obtained from alkyl ketene dimer (AKD) dissolved in scCO2 by this modified RESS technique.

Surface modification of silica particles with organomodified silane derivatives for highly hydrophobic films has been reported by Purcar et al. [32]. The formation of silica nanoparticles using sol-gel synthesis in various conditions of temperature and pressure of CO2 was investigated, both in subcritical and supercritical phases. Tetraethoxysilane (TEOS) was used as the particle precursor and octyltriethoxysilane (OTES) as the co-precursor for coating. The dynamic light scattering measurements show that the higher CO2 pressure leads to larger diameters of coated particles. The agglomeration of the silica nanoparticles was found to be dependent

**173**

cant exfoliation.

**Figure 9.**

*Synthesis and Functionalization of Nanoparticles in Supercritical CO2*

on the temperature and pressure of the CO2 reaction media. The SEM images confirm the tendency of aggregation and differences in the size of silica nanoparticles

*SEM images of coated silica nanoparticles prepared in CO2 in various conditions of temperature and pressure. (1 = 25°C, 6 MPa; 2 = 40°C, 6 MPa; 3 = 60°C, 6 MPa; 4 = 25°C, 7.5 MPa; 5 = 40°C, 7.5 MPa; 6 = 60°C,* 

The size of the resulting silica particles is around 100–250 nm when the CO2 pressure is 6 MPa and decreases up to 150 nm when the CO2 pressure increases to 7.5 MPa. It was observed that the higher CO2 pressure gives narrower size distributions. The thin films obtained by the as-prepared silica nanodispersions deposited on glass substrate show high contact angle values, ranging from 127 to 1450

The NP processing using scCO2 as solvent leads not only to the adequate modification of the surface but, sometimes, also to the decrease of the aggregates and better dispersibility and interaction with polymeric matrix. Wei et al. [33] reported recently the silane modification of graphene nanoparticles for the fabrication of composite polymeric films with superior barrier properties. The obtained graphenes functionalized with silane exhibit a fluffy appearance with small size of sheets. The graphene surface was silanized through the hydrolysis and condensation of different organomodified silane derivatives: aminopropyl triethoxysilane, glycidyloxypropyltrimethoxysilane, and methacryloxy propyl trimethoxysilane. The reaction was conducted in scCO2 for 2 hours at 40**°**C and 20 MPa. The successful formation of SiO2 coating on graphene sheets was proven by FTIR spectra and thermogravimetric analysis and supports the enhanced dispersibility of modified GNs in polymeric membrane, together with a signifi-

Nanoparticle surface functionalization with polymeric shells is an important issue in preparation of biocompatible colloidal vectors in drug delivery that allow further attachment of bioactive ligands. The transfer of such synthesis in scCO2 for the functionalization of nanoparticles used as drug delivery systems in pharmaceutical formulations benefits from the absence of many posttreatment steps that are generally required to remove remaining solvents or nondesirable by-products generated in wet chemistry methods. Marre et al. [34] demonstrated the feasibility

.

coated with octyl-modified derivative (**Figure 9**).

*7.5 MPa). Reprinted with permission from Ref. [32].*

*DOI: http://dx.doi.org/10.5772/intechopen.89353*

### **Figure 9.**

*Advanced Supercritical Fluids Technologies*

terms of control on the size, size distribution, and shape of the final product. The stabilization of such reaction media with low amount of affordable and nontoxic surfactants remains the major bottleneck and limits the extension of this method.

*TEM images of hybrid catalyst Pt-CNT synthesized in various media by (a) water-in-supercritical CO2 microemulsion, (b) water-in-oil microemulsions, (c) direct deposition in supercritical CO2 (adapted with* 

The modification of nanoparticle surfaces, either in solutions or as layers deposited on various surfaces, is a key issue in many processes to fabricate functional materials, in many applications. Commonly used methods for the modification of nanoparticles such as quantum dots, graphene, metallic nanoparticles, etc. are based on solution processing involving organic solvents, which makes the whole process very difficult to implement as eco-friendly technology. For biomedical applications in particular, the proper functionalization of the surfaces in synthesis that involve green solvents is particularly encouraged. Industrial or large-scale processes for the modification of surfaces by vapor-related physical methods suffer from huge limitations due to the high-cost and energy-consuming devices. On the other hand, liquid-related chemical methods have an additional drawback: the solvent removal after the reaction is completed on the targeted surface. Due to the variety of roles that can be attributed to carbon dioxide, i.e., solvent, antisolvent, reaction medium, respectively, unique flexibility for surface engineering is obtained

A variation of RESS method can be applied for coating processes, with the condition that coating material dissolves in scCO2. The solution is introduced via a nozzle in another chamber that contains the solid support to be functionalized. During the rapid depressurization, the density of CO2 changes significantly, and consequently a supersaturation followed by precipitation of the material forming a coating occurs. For example, superhydrophobic coatings on paper were obtained from alkyl ketene dimer (AKD) dissolved in scCO2 by this modified RESS

Surface modification of silica particles with organomodified silane derivatives for highly hydrophobic films has been reported by Purcar et al. [32]. The formation of silica nanoparticles using sol-gel synthesis in various conditions of temperature and pressure of CO2 was investigated, both in subcritical and supercritical phases. Tetraethoxysilane (TEOS) was used as the particle precursor and octyltriethoxysilane (OTES) as the co-precursor for coating. The dynamic light scattering measurements show that the higher CO2 pressure leads to larger diameters of coated particles. The agglomeration of the silica nanoparticles was found to be dependent

**5. Functionalization of nanoparticles in scCO2**

**172**

using scCO2.

**Figure 8.**

*permission from ref. [31]).*

technique.

*SEM images of coated silica nanoparticles prepared in CO2 in various conditions of temperature and pressure. (1 = 25°C, 6 MPa; 2 = 40°C, 6 MPa; 3 = 60°C, 6 MPa; 4 = 25°C, 7.5 MPa; 5 = 40°C, 7.5 MPa; 6 = 60°C, 7.5 MPa). Reprinted with permission from Ref. [32].*

on the temperature and pressure of the CO2 reaction media. The SEM images confirm the tendency of aggregation and differences in the size of silica nanoparticles coated with octyl-modified derivative (**Figure 9**).

The size of the resulting silica particles is around 100–250 nm when the CO2 pressure is 6 MPa and decreases up to 150 nm when the CO2 pressure increases to 7.5 MPa. It was observed that the higher CO2 pressure gives narrower size distributions. The thin films obtained by the as-prepared silica nanodispersions deposited on glass substrate show high contact angle values, ranging from 127 to 1450 .

The NP processing using scCO2 as solvent leads not only to the adequate modification of the surface but, sometimes, also to the decrease of the aggregates and better dispersibility and interaction with polymeric matrix. Wei et al. [33] reported recently the silane modification of graphene nanoparticles for the fabrication of composite polymeric films with superior barrier properties. The obtained graphenes functionalized with silane exhibit a fluffy appearance with small size of sheets. The graphene surface was silanized through the hydrolysis and condensation of different organomodified silane derivatives: aminopropyl triethoxysilane, glycidyloxypropyltrimethoxysilane, and methacryloxy propyl trimethoxysilane. The reaction was conducted in scCO2 for 2 hours at 40**°**C and 20 MPa. The successful formation of SiO2 coating on graphene sheets was proven by FTIR spectra and thermogravimetric analysis and supports the enhanced dispersibility of modified GNs in polymeric membrane, together with a significant exfoliation.

Nanoparticle surface functionalization with polymeric shells is an important issue in preparation of biocompatible colloidal vectors in drug delivery that allow further attachment of bioactive ligands. The transfer of such synthesis in scCO2 for the functionalization of nanoparticles used as drug delivery systems in pharmaceutical formulations benefits from the absence of many posttreatment steps that are generally required to remove remaining solvents or nondesirable by-products generated in wet chemistry methods. Marre et al. [34] demonstrated the feasibility

### **Figure 10.**

*The variation of polymeric shell thicknesses on nanoparticles as a function of the initial mass fraction of polymer in the initial solution (reprinted with permission from ref 34).*

of a versatile method for coating silica particles used as model substrates, with either a hydrophilic (polyethylene glycol PEG) or hydrophobic polymer (hydroxyl-terminated polybutadiene, HTPB) using a supercritical antisolvent process (**Figure 10**).

The principle of the precipitation from compressed antisolvent PCA techniques is allowing the contact of the polymeric solution with the scCO2 as antisolvent, when a succession of different phenomena governed by hydrodynamic, precipitation kinetics, thermodynamic, and mass-transfer effects result eventually in the precipitation of an organic shell on the nanoparticles dispersed previously in the polymeric solution. According to the polymer used (PEG or PBHT) and the reaction conditions, various sizes of the deposited polymeric shell have been obtained, from 3 to 28 nm, by simply modification of polymer concentration in the initial solution (**Figure 10**).

In order to effectively exploit the advantages of "green" processing in scCO2, Roy et al. describe the successful grafting of a model drug (salicylic acid, SA) on TiO2 nanoparticles [35]. The chosen active compound could react with the nanoparticle surfaces through the carboxylic and hydroxyl groups. The functionalization of the TiO2 surface was performed in mild conditions, at 40**°**C and 16 MPa for a short period of time, up to 2 hours. The thermogravimetric analysis shows a calculated amount of drug SA deposited on TiO2 nanopowder of approximately 8 wt%, and the SEM images of coated samples do not reveal rod-like crystals specific for solid salicylic acid, which confirm the absence of residual drug other than the coating deposited on nanoparticles.

In the last decades, methods to perform functionalization of nanoparticles using scCO2 were reported, as viable alternative to classical synthesis and showing remarkable advantage of reduced impact on the environment.

### **6. Conclusion**

The recent works in supercritical fluids demonstrate the multiplicity of advantages in synthesis of nanomaterials, either organic or inorganic. Complex synthesis of hybrid materials consisting in nanoparticles deposited on other structures (carbon nanotubes) or core-shell nanoparticles was also developed in scCO2.

**175**

*Synthesis and Functionalization of Nanoparticles in Supercritical CO2*

An important problem that requires further research, especially for fine-tuning the nanoparticle size, is design and fabrication of CO2-philic surfactants that enable the formation of water-in-scCO2 microemulsion as reaction media. The successful synthesis of nontoxic and cost-effective surfactants will open the opportunity to extend this method to many nanoparticles used as drug delivery vehicles, where the

Another domain which is expected to benefit from further research in order to advance this technology is the development of novel strategy for surface functional-

This work was supported by grants of the Romanian National Authority for Scientific Research and Innovation, CCCDI - UEFISCDI, project number PN-III-P1- 1.2-PCCDI-2017-0743/P5, and PN-III-P1-1.2-PCCDI-2017-0428/P2 within PNCDI III.

W maximum water content in microemulsion, expressed as water-to-

DESAM depressurization of an expanded solution into an aqueous medium

surfactant molar ratio [H2O]/[surfactant]

δ polymeric shell thicknesses on nanoparticles, nm

ξ initial mass fraction of polymer, %

AOT sodium bis-(2-ethylhexyl) sulfosuccinate

FTIR Fourier-transform infrared spectroscopy

PDMAEMA poly(N,N-dimethylaminoethyl methacrylate)

POEGMA poly(oligo(ethylene glycol) methacrylate)

PAM 2-Pyridinealdoxime methochloride PBHT polybutadiene hydroxy terminated

*DOI: http://dx.doi.org/10.5772/intechopen.89353*

size and size distribution control are a key issue.

The authors have no conflict of interest to declare.

ization, especially for scalable processes.

**Acknowledgements**

**Conflict of interest**

**Nomenclature**

*p* pressure, MPa *T* temperature, K

λ wavelength, cm<sup>−</sup><sup>1</sup>

AKD alkyl ketene dimer

DSC dynamic light scattering

PCL poly(ε-caprolactone)

PEG polyethylene glycol PLA polylactic acid

PLGA poly(lactic-coglycolic) PMMA poly(methyl methacrylate)

*t* time, s

cr critical

Chi chitosan

GNs graphene NPs nanoparticles OTES octyltriethoxysilane

Acronyms

*Synthesis and Functionalization of Nanoparticles in Supercritical CO2 DOI: http://dx.doi.org/10.5772/intechopen.89353*

An important problem that requires further research, especially for fine-tuning the nanoparticle size, is design and fabrication of CO2-philic surfactants that enable the formation of water-in-scCO2 microemulsion as reaction media. The successful synthesis of nontoxic and cost-effective surfactants will open the opportunity to extend this method to many nanoparticles used as drug delivery vehicles, where the size and size distribution control are a key issue.

Another domain which is expected to benefit from further research in order to advance this technology is the development of novel strategy for surface functionalization, especially for scalable processes.
