Preparation of mesoporous silica nanoparticles by spray drying

Abstract

Mesoporous silica nanoparticles (MSNs) are usually obtained by conventional sol-gel synthesis techniques, in a process that requires long reaction periods, and goes through many critical steps. Small variation in the synthesis conditions can modify the morphology, structural and textural properties of materials. An alternative route for silica nanoparticles manufacturing is the spray drying (SD) technique, which involves particle formation by evaporation-induced hydrolysis and condensation of silicates, also providing continuous production. In this context, we have developed a new SD-based methodology for the preparation of well-dispersed MSNs by properly adjusting the pH of the synthesis mixture (e.g., pH=8.5), and using NaF as silica mobilizing agent. These nanoparticles present wormhole-like pores that are randomly distributed in all directions and hexagonal symmetry easily recognizable in the mesoporous wall at small domains. In addition, optimizing the gas inlet temperature (T_in) to 90ºC promoted rapid assembly between silicate network building species during the SD process, yielding nanoparticles with good structural and textural properties. This technique is highly scalable and adaptable to the industrial stage, showing enormous interest in the pharmaceutical development.

Highlights

• Spray drying (SD) as an alternative route for the synthesis of mesoporous silica nanoparticles.
• Optimization of silica mobilizing agent for SD-synthesis of mesoporous silica nanoparticles.
• Optimization of gas inlet temperature for SD-synthesis of mesoporous silica nanoparticles.

Introduction

Mesoporous silica nanoparticles with MCM-41-type structure (MSNs) are characterized by large surface area and large pore volume, uniform and modulable pore size, easy surface functionalization (both internal and external) of the pores, and a rigid and stable hexagonal ordering [1]. MSNs are also very robust and present the ability to encapsulate metals and molecules within their pore channels [2], [3]. These properties give MSNs potential applications in catalysis [4], [5], separation [6], adsorption of chemicals [7] and biomedicine [8], [9]. In the case of the biomedical scope, these MSNs can be utilized for the preparation of controlled drug delivery systems sensitive to chemical stimuli (pH, enzymes, redox compounds) or physical activation (temperature, light, magnetism and ultrasounds). MSN can also be used as multifunctional nanoplatforms encapsulating various contrast agents for subsequent diagnostic and imaging modalities, such as magnetic resonance imaging (MRI), optical/fluorescence, positron emission tomography (PET) and multimodality imaging [9], [10]. In addition, these nanoparticles can effectively transport biomolecules such as nucleic acids and proteins conferring protection against enzymatic degradation [11]. However, the production of MSNs requires of conventional sol-gel synthesis techniques, in a process that takes long reaction periods, and goes through many critical steps (e.g., templating, nucleation, condensation, aging, separation, drying and template removal). Small variation in the synthesis conditions can condition the morphology, structural and textural properties of materials [12], [13]. For example, the alkaline pH setting is critical, as lower initial pH results in amorphous nanoparticles, while a higher initial pH produces larger particles, and too high a pH often results in particle agglomeration [14]. In addition, reaction temperature and surfactant concentration are other important parameters that influence the size and morphology of MSNs and are also known to alter the rate of hydrolysis and condensation rate of the silica precursor.
In this context, an alternative route recently developed for silica nanoparticles manufacturing is the spray drying (SD) technique [15]. This method involves particle formation through an evaporation-induced silicate hydrolysis and condensation. The process allows quick preparation of uniformly spherical silica particles in hydroalcoholic media from submicron to micron sizes, although different morphologies can be obtained by changing the solvent [16], and provides continuous production with strong potential for industrial scaling, which shows enormous interest in the pharmaceutical development [17]. Furthermore, currently, there is laboratory-scale equipment for the production of silica nanoparticles, as the Nano Spray Dryer B-90 introduced by BUCHI Labortechnik AG in 2009, which is able to produce spray-dried particles in the submicron scale with a narrow size distribution [18].

With regards to the preparation of mesoporous silica particles, some groups have succeed obtaining SBA-15 microspheres by SD with specific macroscopic properties [16], [19], and also controlling the incorporation of drugs into the mesopores [16]. Nevertheless, the synthesis of MSNs by this method encounters several constrains, such as: i) the difficulties to assemble silicate anions and templating molecules in very short time leading to a partially structured material; ii) strong nanoparticle aggregation; and iii) technical limitations of the vibrating mesh spray technology, which can’t be exposed to solutions of pH>8.5. This last condition becomes critical because, as extensively studied by Varache et al. [20], the optimal NaOH concentration for MSNs preparation is between 10 and 15 mM, with a pH set at 11.8.

It is possible to craft mesoporous molecular sieves by sol-gel condensation at almost neutral pH by using low molecular weight amines (e.g., ethanolamine) as silica activator [21]. Moreover, MCM-41 mesophase has also been synthesized with long-range structural order at low pH by using fluoride ions as mineralizing agent [22], [23]. Therefore, we here present a new methodology based in SD for the preparation of well-dispersed MSNs with appropriate pH adjustment of the synthesis mixture (e.g., pH=8.5), and using different catalysts for silica activation, as NaOH, ethanolamine (ETA) or NaF. To our knowledge, this is the first successful attempt of synthesizing MSNs by the SD route starting from building components (e.g., silica source and templating agent), to give single nanoparticles with wormhole-like pores and hexagonal mesophase at small domains.

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Lucía Gómez, Eva María Rivero-Buceta, Carla Vidaurre-Agut, Pablo Botella, Preparation of mesoporous silica nanoparticles by spray drying, Microporous and Mesoporous Materials, 2025, 113646, ISSN 1387-1811, https://doi.org/10.1016/j.micromeso.2025.113646.

Read also our introduction article on Mesoporous Silica here: