Synthesis of ordered mesoporous silica MCM-41 with controlled morphology for potential application in controlled drug delivery systems

Cerâmica 65 (2019) 170-179 170 http://dx.doi.org/10.1590/0366-69132019653742509 Synthesis of ordered mesoporous silica MCM-41 with controlled morphology for potential application in controlled drug delivery systems (Síntese de sílica mesoporosa ordenada tipo MCM-41 com controle morfológico para potencial aplicação em sistemas de liberação controlada de fármacos) D. M. Oliveira1, A. S. Andrada1* Universidade Federal de Itajubá, R. Irmã Ivone Drumond 200, 35903-087, Itabira, MG, Brazil 1 Abstract MCM-41 is one of the most studied mesoporous ceramics for drug delivery systems. Its high specific surface area and mesoporosity allow high adsorption capacity. Even though there are many studies published in the biomedical field, there are no reports of commercial applications of MCM-41 so far. One of the possible justifications is the lack of morphological control during conventional synthesis. Therefore, modifications in the reaction parameters of the MCM-41 conventional synthesis were tested in this paper, aiming to obtain particles with reduced diameter and agglomeration. It was observed that both the increase in the water molar proportion and the decrease in the stirring time resulted in particles with reduced size. Furthermore, the control of the tetraethyl orthosilicate (TEOS) dropping rate and the addition of triethylamine (TEA) improved the dispersion of the system, but they also decreased the particle size, and therefore van der Waals interactions promoted re-agglomeration. Keywords: MCM-41, controlled drug release, reduction of particle size, increase in dispersion. Resumo O MCM-41 é uma das cerâmicas mesoporosas mais estudadas para sistemas de liberação controlada de fármacos. Sua elevada área superficial específica e mesoporosidade permitem alta capacidade de adsorção. Apesar dos inúmeros trabalhos publicados na área biomédica, até o presente momento não há relatos de aplicações comerciais do MCM-41. Uma possível justificativa é a falta de controle morfológico durante a síntese convencional. Portanto, modificações nos parâmetros reacionais da síntese convencional do MCM-41 foram testadas neste artigo com o objetivo de obter partículas com diâmetro e estado de aglomeração reduzidos. Foi observado que o aumento na proporção molar de água e a diminuição no tempo de agitação resultaram em partículas com tamanho reduzido. Além disso, o controle do gotejamento do tetraetilortossilicato (TEOS) e a adição da trietilamina (TEA) melhoraram a dispersão do sistema, porém eles também reduziram o tamanho das partículas e, assim, interações do tipo van der Waals promoveram a reaglomeração. Palavras-chave: MCM-41, liberação controlada de fármacos, redução de tamanho de partículas, aumento da dispersão. INTRODUCTION Ordered mesoporous ceramics are characterized by the presence of ordered porosity, with a diameter between 2 and 50 nm, but disordered silica walls [1]. Those materials were first developed in the 1990’s aiming to increase the diameter of zeolites pores and enable its application in adsorption and catalysis. In 1992, scientists from Mobil Oil Co. synthesized ordered mesoporous materials of the M41S type, family to which MCM-41 belongs using surfactants to promote the formation of porous structures. Instead of * https://orcid.org/0000-0002-6884-8345 using small organic molecules as templating compounds, as in the case of zeolites, long chain surfactant molecules were employed as the structure-directing agent during the synthesis of these highly ordered materials [1]. Currently, there are many families of mesoporous materials, which are produced by distinct synthesis methods and reactants. The most frequently reported families are MCM-n (Mobil Corporation Matter), SBA-n (Santa Barbara), MSU-n (Michigan State University), KIT-n (Korean Institute of Technology), FSM-n (folded sheet materials), FDU (Fudan University) and AMS-n (anionic mesoporous silica) [1]. Despite starting in the catalysis industry, mesoporous materials, especially MCM-41, have been explored for applications in the biomedical area, as scaffolds for tissue D. M. Oliveira et al. / Cerâmica 65 (2019) 170-179 engineering, in gene therapy, anti-cancer therapy, and drug delivery systems. Those applications are possible because of the unique properties of the mesoporous ceramics, which include high specific surface area and pore volume, biocompatibility in vitro and in vivo, bioactivity, thermal and chemical stability, tunable particle and pore size, and the possibility of functionalization [1, 2]. Vallet-Regi and coworkers [3] were pioneers in the studies of MCM41 as potential materials for controlled drug delivery. The interest in drug delivery systems is justified by the necessity of improving the therapeutic response of conventional medicines. Advantages of drug delivery systems over traditional systems include the ability to deliver drugs to a specific site, the small variability in systemic drug concentrations and the reduction in toxic metabolites. Nowadays, MCM-41 is one of the most studied mesoporous ceramics to be employed as a matrix for controlled drug release. Particularly, its high specific surface area provides the possibility to load a high amount of drugs on its surface [4], leading to a more efficient system. In addition, its mesoporosity allows the encapsulation of molecules or mixture of molecules with variable diameter, shape, and functionality. Even though there are many scientific projects being developed in the field of controlled drug delivery, commercial applications of MCM-41 were not reported so far. One of the possible justifications is the lack of morphological control when using conventional methods to synthesize mesoporous ceramics; particles with various size and shape are obtained. Consequently, the properties of mass transfer at the nanometric level are affected, and they are fundamental to the controlled release and delivery of drugs in biological systems [5]. The size of the mesoporous silica particles has a fundamental role in the absorption and capture of the material by the cells, in the penetration through tissues, in the accumulation of particles in non-target organs, in the time for circulation in the bloodstream, and in the release rate of the drug adsorbed on the external or internal surface of the pores [2, 6]. Therefore, the control of the particle size during the synthesis is essential to obtain efficient drug delivery systems. For biomedical applications, it is desired to obtain uniform nanoparticles with 50 to 300 nm in diameter since larger particles may not be able to cross physical membranes in the body and smaller particles are harder to synthesize keeping their mesoporosity [7]. Another factor that needs to be controlled during the synthesis of ordered mesoporous materials is the agglomeration of particles. When the size is reduced, Brownian motion and van der Waals forces act more intensely, increasing the contact and interaction between particl (...truncated)