**4. Outlooks and perspectives**

Here I focus on the state-of-the-art research on nanotechnology that involves the microemulsion method.

Chen et al. [29] reported the synthesis of CdS QDs by means of a chemical reaction between amide of cadmium acetate dehydrate and thioacetamide by using a microemulsion-based hydrothermal method. Their properties could be tailored through the use of Emulsifier OP and CTAB, which yield a usual cubic phase and a scarce hexagonal phase, apiece. Authors explored a possible mechanism involving the critical role of surfactant in the formation of crystal structure. A direct dependence of the crystal size that regularly increased with the increase of temperature is also found, and the appearance of red shift in the absorption and emission peaks confirmed the quantum confinement effect. All the desired properties of CdS QDs synthesized by this route denote the chance of the preparation of high-quality QDs under the appropriate reaction conditions.

First, aqueous solutions 0.005 M of cadmium acetate and thioacetamide were set by melting in deionized water with the aid of magnetic stirrer. Next, two reverse microemulsions (MCd and MS) with different aqueous phases were prepared. Either MCd or MS enclosed three mutual constituents in the volume ratio of 3:5:20, that is, a surfactant of CTAB or emulsifier OP, co-surfactant of n-butyl alcohol, and a continuous oil phase of n-hexane. Once jointly mixed under constant stirring at r.t. during 30 min, it was moved into a 100 mL Teflon-lined autoclave with hydrothermal treatment at 70–120°C for 13 h, succeeded by chilling at r.t. readily. The yellow precipitants were harvested from the synthesis medium by centrifugation, cleaned with anhydrous ethanol and deionized water sometimes and then dried at 70°C, to finally obtain CdS QDs.

The crystal structure was characterized by XRD, obtaining OP at 2θ values of 26.5, 43.9, and 52.1° which agree with the (1 1 1), (2 2 0), and (3 1 1) planes of cubic structure. The morphology was analyzed with a transmission electron microscope, denoting that at 70°C, the mean crystal size of CdS QDs is much tinier (≈3 nm), and afterward it achieved 5.9 nm, when the temperature was increased to 120°C. It noticeably proved the influence of reaction temperature on the crystal size of the as-prepared CdS QDs. The optical properties of samples were characterized by the UV-4100 spectrophotometer and FLS920 steady-state and transient fluorescence spectrometer. In addition, infrared spectroscopy was recorded.

Wei et al. [30] reported the synthesis of the core-shell NaGdF4@CaCO3-PEG NPs were carried out through a facile microemulsion method with using NaGdF4 NPs as templates [31]. Concisely, 5 mL NaGdF4 NPs, 10 mL of cyclohexane, 3.45 mL of Triton X-100, and 3.2 mL of 1-hexanol were added to a flask and combined carefully, followed by annexing 800 μL of a 30 mM solution of CaCl2 to obtain a well-dispersed *w/o* microemulsion. Before the 40 μL, 2.92 M solution of sodium carbonate was added. The microemulsion was kept under mild stirring for 8 h of the mix; the NaGdF4@CaCO3 NPs were gathered by centrifugation and next redispersed in 10 mL of ultrapure water. Afterward, 2 mL and 0.2 M PEG8000 (aq.) solution was annexed and stirred for additional 8 h, and subsequently the NPs were gathered by using centrifuge at 10,000 r.p.m. during 15 min and re-dispersed in 20 mL of ultrapure water for further purpose.

**85**

*Synthesis of NPs by Microemulsion Method DOI: http://dx.doi.org/10.5772/intechopen.80633*

In this work, a core-shell nanoparticle of NaGdF4@CaCO3-PEG was designed as an activable MR/US dual-modal imaging contrast for cancer diagnosis, which is activated by the acidic environment. Authors used the coating of NaGdF4 with a layer of hydrophobic CaCO3 to limit water availability, thus quenching the sphere Gd3+ relaxation effects, with the aim of achieving this OFF/ON responsive MR imaging behavior. At acidic aqueous solution, CaCO3 was melted to produce CO2 bubbles, which is applied to obtain US signal. While a robust MRI augmentation could be triggered on dissolution of CaCO3 and discharge of the earlier quieted NaGdF4 in the aqueous solution. In vivo results confirmed the heavy dual-modal magnetic resonance/ ultrasonic imaging capabilities of NaGdF4@CaCO3-PEG at the tumor area with an acidic environment. Authors expected that their findings might deliver a novel sight for approaches to developing NPs with reactive dual-modal imaging skills. The heredescribed proof-of-concept nanoparticles with pH-triggered magnetic resonance/ ultrasonic dual-modal imaging improvement may assist as a useful guide to advance

Majumder and Roy reported the synthesis of mesoporous CeO2 nanospheres [32] with noticeably raised surface area. It was ready using reversed micelles by a waterin-oil microemulsion method. The structure and semiconducting properties of the NPs are accurately explored using TEM, FESEM, XRD, and UV-Vis. Despite after high-temperature burning, the structural holding of the nanomaterial was evident by EM. Comparing to those of other sensors of the same type, outstanding performances in terms of sensitivity, response-recovery times, and selectivity were found on the distribution of undoped CeO2 nanospheres for the detection of low-ppm CO. These CO sensors showed 52% sensitivity with a reply time of only 13 s. The sensor parameters were analyzed as a function of both gas concentration and temperature. In addition to that on the scalable and cost-effective synthesis of CeO2 nanospheres, authors also reported on the fabrication of packaged CO sensors, which could be potentially used for industrial and environmental monitoring purposes. To carry out the material synthesis, all of the chemicals (analytical grade) were applied without further treatment. Primarily, a microemulsion was formed by merging n-hexane, n-butyl alcohol, and diethyl ether in the weight ratio 3:2:1, energetically stirred till the mix turns out to be clear. The quantity of CTAB to reach critical micelle concentration (CMC) was calculated applying the standard conductometric method, where a sequence of microemulsions were examined changing the [CTAB] between 0.2 and 1.5 g. Then, 10 mL of 1 M aqueous solution of Ce(NO3)3 including 0.65 g of CTAB was annexed to the mix, and then it was agitated again till it showed transparency. Concurrently, another aqueous solution of 10% (w/v) NH4OH was prepared. The above solutions were merged strongly till it forms a colloidal suspension. The material was gathered by centrifugation at 6000 r.p.m. during 30 min and consecutively washed using deionized water in an ultrasonic bath during 2 h. Lastly, the collected material was

Wang et al. reported the synthesis and applications of new biomimetic hybrid nanoplatform with theranostic agents [33]. Authors reported the synthesis of this nanoplatform; it was out by the next method: Silica NP core was used to encapsulate fullerene (C60) by a reverse microemulsion method. First, hexanol, Triton X-100, cyclohexane, and deionized water were jointly mixed. A total volume of 2 mL of

60 mL of ammonium hydroxide solution (28 wt%) and 100 mL TEOS were serially annexed, and the sample was rattled at 800 r.p.m. using a mini-stir bar during 24 h at r.t. Finally, the sample was annexed in 30 mL of ethanol to cease the reaction. The obtained sample was centrifuged at 13,800 × g during 10 min to attain fullereneinserted silica C60S-NPs. After twofold cleaning with deionized water and ethanol, the NPs were suspended in 3 mL of ethanol and followed by the addition 20 mL of

) was then added into the mixture. Subsequently,

various molecular imaging strategies for cancer diagnosis in the future.

dried under vacuum and calcined at 600°C during 4 h.

fullerene in toluene (2 mg mL<sup>−</sup><sup>1</sup>

#### *Synthesis of NPs by Microemulsion Method DOI: http://dx.doi.org/10.5772/intechopen.80633*

*Microemulsion - A Chemical Nanoreactor*

**4. Outlooks and perspectives**

under the appropriate reaction conditions.

microemulsion method.

finally obtain CdS QDs.

uniqueness, TPAOH content, and the presence of salts and co-surfactant influence the morphology and crystallinity of silicalite-1. The crystal size and shape contrasted in all cases than those prepared in default of the microemulsion. The crystal morphology could be regulated by adjusting the interplay among surfactant and zeolite surfaces.

Here I focus on the state-of-the-art research on nanotechnology that involves the

Chen et al. [29] reported the synthesis of CdS QDs by means of a chemical reaction between amide of cadmium acetate dehydrate and thioacetamide by using a microemulsion-based hydrothermal method. Their properties could be tailored through the use of Emulsifier OP and CTAB, which yield a usual cubic phase and a scarce hexagonal phase, apiece. Authors explored a possible mechanism involving the critical role of surfactant in the formation of crystal structure. A direct dependence of the crystal size that regularly increased with the increase of temperature is also found, and the appearance of red shift in the absorption and emission peaks confirmed the quantum confinement effect. All the desired properties of CdS QDs synthesized by this route denote the chance of the preparation of high-quality QDs

First, aqueous solutions 0.005 M of cadmium acetate and thioacetamide were set by melting in deionized water with the aid of magnetic stirrer. Next, two reverse microemulsions (MCd and MS) with different aqueous phases were prepared. Either MCd or MS enclosed three mutual constituents in the volume ratio of 3:5:20, that is, a surfactant of CTAB or emulsifier OP, co-surfactant of n-butyl alcohol, and a continuous oil phase of n-hexane. Once jointly mixed under constant stirring at r.t. during 30 min, it was moved into a 100 mL Teflon-lined autoclave with hydrothermal treatment at 70–120°C for 13 h, succeeded by chilling at r.t. readily. The yellow precipitants were harvested from the synthesis medium by centrifugation, cleaned with anhydrous ethanol and deionized water sometimes and then dried at 70°C, to

The crystal structure was characterized by XRD, obtaining OP at 2θ values of 26.5, 43.9, and 52.1° which agree with the (1 1 1), (2 2 0), and (3 1 1) planes of cubic structure. The morphology was analyzed with a transmission electron microscope, denoting that at 70°C, the mean crystal size of CdS QDs is much tinier (≈3 nm), and afterward it achieved 5.9 nm, when the temperature was increased to 120°C. It noticeably proved the influence of reaction temperature on the crystal size of the as-prepared CdS QDs. The optical properties of samples were characterized by the UV-4100 spectrophotometer and FLS920 steady-state and transient fluorescence

Wei et al. [30] reported the synthesis of the core-shell NaGdF4@CaCO3-PEG NPs were carried out through a facile microemulsion method with using NaGdF4 NPs as templates [31]. Concisely, 5 mL NaGdF4 NPs, 10 mL of cyclohexane, 3.45 mL of Triton X-100, and 3.2 mL of 1-hexanol were added to a flask and combined carefully, followed by annexing 800 μL of a 30 mM solution of CaCl2 to obtain a well-dispersed *w/o* microemulsion. Before the 40 μL, 2.92 M solution of sodium carbonate was added. The microemulsion was kept under mild stirring for 8 h of the mix; the NaGdF4@CaCO3 NPs were gathered by centrifugation and next redispersed in 10 mL of ultrapure water. Afterward, 2 mL and 0.2 M PEG8000 (aq.) solution was annexed and stirred for additional 8 h, and subsequently the NPs were gathered by using centrifuge at 10,000 r.p.m. during 15 min and re-dispersed in

spectrometer. In addition, infrared spectroscopy was recorded.

20 mL of ultrapure water for further purpose.

**84**

In this work, a core-shell nanoparticle of NaGdF4@CaCO3-PEG was designed as an activable MR/US dual-modal imaging contrast for cancer diagnosis, which is activated by the acidic environment. Authors used the coating of NaGdF4 with a layer of hydrophobic CaCO3 to limit water availability, thus quenching the sphere Gd3+ relaxation effects, with the aim of achieving this OFF/ON responsive MR imaging behavior. At acidic aqueous solution, CaCO3 was melted to produce CO2 bubbles, which is applied to obtain US signal. While a robust MRI augmentation could be triggered on dissolution of CaCO3 and discharge of the earlier quieted NaGdF4 in the aqueous solution. In vivo results confirmed the heavy dual-modal magnetic resonance/ ultrasonic imaging capabilities of NaGdF4@CaCO3-PEG at the tumor area with an acidic environment. Authors expected that their findings might deliver a novel sight for approaches to developing NPs with reactive dual-modal imaging skills. The heredescribed proof-of-concept nanoparticles with pH-triggered magnetic resonance/ ultrasonic dual-modal imaging improvement may assist as a useful guide to advance various molecular imaging strategies for cancer diagnosis in the future.

Majumder and Roy reported the synthesis of mesoporous CeO2 nanospheres [32] with noticeably raised surface area. It was ready using reversed micelles by a waterin-oil microemulsion method. The structure and semiconducting properties of the NPs are accurately explored using TEM, FESEM, XRD, and UV-Vis. Despite after high-temperature burning, the structural holding of the nanomaterial was evident by EM. Comparing to those of other sensors of the same type, outstanding performances in terms of sensitivity, response-recovery times, and selectivity were found on the distribution of undoped CeO2 nanospheres for the detection of low-ppm CO. These CO sensors showed 52% sensitivity with a reply time of only 13 s. The sensor parameters were analyzed as a function of both gas concentration and temperature. In addition to that on the scalable and cost-effective synthesis of CeO2 nanospheres, authors also reported on the fabrication of packaged CO sensors, which could be potentially used for industrial and environmental monitoring purposes. To carry out the material synthesis, all of the chemicals (analytical grade) were applied without further treatment. Primarily, a microemulsion was formed by merging n-hexane, n-butyl alcohol, and diethyl ether in the weight ratio 3:2:1, energetically stirred till the mix turns out to be clear. The quantity of CTAB to reach critical micelle concentration (CMC) was calculated applying the standard conductometric method, where a sequence of microemulsions were examined changing the [CTAB] between 0.2 and 1.5 g. Then, 10 mL of 1 M aqueous solution of Ce(NO3)3 including 0.65 g of CTAB was annexed to the mix, and then it was agitated again till it showed transparency. Concurrently, another aqueous solution of 10% (w/v) NH4OH was prepared. The above solutions were merged strongly till it forms a colloidal suspension. The material was gathered by centrifugation at 6000 r.p.m. during 30 min and consecutively washed using deionized water in an ultrasonic bath during 2 h. Lastly, the collected material was dried under vacuum and calcined at 600°C during 4 h.

Wang et al. reported the synthesis and applications of new biomimetic hybrid nanoplatform with theranostic agents [33]. Authors reported the synthesis of this nanoplatform; it was out by the next method: Silica NP core was used to encapsulate fullerene (C60) by a reverse microemulsion method. First, hexanol, Triton X-100, cyclohexane, and deionized water were jointly mixed. A total volume of 2 mL of fullerene in toluene (2 mg mL<sup>−</sup><sup>1</sup> ) was then added into the mixture. Subsequently, 60 mL of ammonium hydroxide solution (28 wt%) and 100 mL TEOS were serially annexed, and the sample was rattled at 800 r.p.m. using a mini-stir bar during 24 h at r.t. Finally, the sample was annexed in 30 mL of ethanol to cease the reaction. The obtained sample was centrifuged at 13,800 × g during 10 min to attain fullereneinserted silica C60S-NPs. After twofold cleaning with deionized water and ethanol, the NPs were suspended in 3 mL of ethanol and followed by the addition 20 mL of

APTMS. The mixture was stirred using a mini-stir bar (200 r.p.m., during 12 h) at room temperature to acquire the APTMS-coated C60S, C60S-A NPs. Lastly, the sample of C60S-A NPs was merged with DPPC liposomes and shacked for 5 h (r.t.) to harvest the phospholipid bilayer-coated C60S, LC60S-NPs. The LC60S NPs were gathered by centrifuging at 13,800 × g for 10 min. The DPPC liposomes were prepared by hydrating a thin DPPC film. Subsequently sonication for 2 min using a Branson 450 Sonifier, the sample of DPPC (1,2-dihexadecanoyl- sn-glycero-3-phosphocholine) liposomes (≈100 nm) was filtered throughout a 0.2 mm filter earlier mixing with the solution of C60S-A nanoparticles. I carried out a research on re-dispersion and self-assembly of C60 pointed special performance and arrangement depending on the solvent nature [34].

Authors concluded that both the encapsulation efficiency (EE) and minimal drug loading content (LC) of theranostic agents are vital calibers of multifunctional NPs for drug transfer. To attain great EE, low drug-to-NP provision ratios have frequently been applied for encapsulation, which outcomes in low drug LC. Authors designed a eukaryotic cell-like nanoplatform or EukaCell, which can be applied to attain great EE (≈100%) and LC (up to ≈87%) of theranostic agents (DOX and ICG). The release of the encapsulated drug can be exactly controlled using NIR laser irradiation to minimize the potential side effects. With the biomimetic eukaryotic cell-like configuration, the EukaCell had an extended half-life and strong stability in blood circulation and could favorably accumulate in tumor following intravenous injection. Finally, the drug-laden EukaCell displayed excellent safety and efficacy for cancer therapy. Authors demonstrated the tremendous potential of their EukaCell for providing theranostic agents to detect and treat cancer.

Tianimoghadam and Salabat reported the formulation of new microemulsion to prepare thiol-functionalized AuNPs [35]. The microemulsion system was obtained by mixing a yellow aqueous solution of 0.03 M of HAuCl4 and a 0.05 M solution of TOAB/toluene. The same microemulsion containing 0.4 M of NaBH4 was prepared independently and drop-wised under energetic stirring into the microemulsion enclosing metal ions. The formation of AuNPs was confirmed by the appearance of a stable light-ruby-red color resulting in microemulsion when the reduced Au(III) ions changed. To form a thiol monolayer surrounding the AuNPs, dodecanethiol (17 mg) was added while kept stirring during 1 h. To eliminate all residual TOAB surfactants (see TOAB chemical structure in **Figure 10**) and thiols from the AuNP surfaces, the AuNPs were pipetted into a 10 mL vial along with 3 mL ethanol and then centrifuged. This procedure was sixfold repeated, after which the dodecanethiol-stabilized AuNPs were then resuspended in toluene. The stable nanocolloid system of Au/toluene was then prepared for characterization. To confirm the size distribution and formation of the AuNPs, TEM techniques and UV-Vis absorption were used. The absorption maximum was found to be 524 nm, which is a shift typical for spherical AuNPs. This surface plasmon band agrees to 3–4 nm particles. According to the Mie theory, the purification procedure removed the

**87**

*Synthesis of NPs by Microemulsion Method DOI: http://dx.doi.org/10.5772/intechopen.80633*

**5. Conclusions**

monodispersed NPs.

**Acknowledgements**

**Conflict of interest**

low-molar-mass impurities without essentially varying the structure of the NPs. The AuNPs were basically spherical and monodispersed with diameters around 3–4 nm. Authors discussed an easy method to prepare dodecanethiol-stabilized AuNPs

As this review chapter has stated, microemulsion method must be taken into account when the aim of the researcher is to prepare well-controlled, narrow-sized,

The influence of microemulsion components has been reviewed; not only the ratio between aqueous phase/surfactant and surfactant/metal precursor but also the influence of the nature of the surfactant—ionic, cationic, and nonionic surfactants—will offer different self-assembled systems. It was underlined that hydrodynamic radius (*rW* = 1.5 *W*) of the microdroplets that forms the microemulsion essentially depends on *W* = [water/surfactant] so the size of our template will be defined by this relation and microdroplet will offer a well-defined microenvironment to prepare NPs. The influence of the tensioactive nature was also considered by the interaction with metal precursors, co-surfactant, during the nucleation and growth processes and consequent influence upon surficial charge of the NPs. Thus the influence of the reagents and its proportions or ratio will determine the size of water pool within the microdroplets, which finally determine size, shape, morphology, and crystalline structure of the NPs. The control of the reaction time, the temperature, and reagent nature and ratios between them will give us a production of different geometries that will find different applications in wide range of research fields, such as chemical sensors, CO sensing, applications on drug delivery and theranostic, quantum dots, MRI, and biomedicine. It can be concluded that

microemulsion method actually offers a good route for synthesis of NPs.

who was a great support during my formation as scientist.

Author does not declare conflict of interest.

Dr. A. Cid acknowledges the postdoctoral contract granted to CIA research group by FEDER Funds at Physical Chemistry Department Universidade de Vigo and the Unidade de Ciências Biomoleculares Aplicadas-UCIBIO which is financed by national funds from FCT/MEC (UID/Multi/04378/2013) and cofinanced by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145- FEDER-007728). This chapter is dedicated to Professor Julio Casado Linarejos,

through a new microemulsion TOAB cationic surfactant-based system. This approach was related with the liquid-liquid phase method. Both AuNPs arranged by different procedures were studied with UV-Vis spectroscopy and TEM imaging, denoting good steadiness. The TEM images of the thiol-capped AuNPs ready by the microemulsion method showed a more acute monodispersity related to that prepared using the Brust method. Since all the methods could be carried out in one

step, the microemulsion procedure was faster and easier.

**Figure 10.** *TOAB chemical structure.*

#### *Synthesis of NPs by Microemulsion Method DOI: http://dx.doi.org/10.5772/intechopen.80633*

low-molar-mass impurities without essentially varying the structure of the NPs. The AuNPs were basically spherical and monodispersed with diameters around 3–4 nm.

Authors discussed an easy method to prepare dodecanethiol-stabilized AuNPs through a new microemulsion TOAB cationic surfactant-based system. This approach was related with the liquid-liquid phase method. Both AuNPs arranged by different procedures were studied with UV-Vis spectroscopy and TEM imaging, denoting good steadiness. The TEM images of the thiol-capped AuNPs ready by the microemulsion method showed a more acute monodispersity related to that prepared using the Brust method. Since all the methods could be carried out in one step, the microemulsion procedure was faster and easier.
