Aerosol-Assisted Synthesis of Tailor-Made Hollow Mesoporous Silica Microspheres for Controlled Release of Antibacterial and Anticancer Agents

Abstract

Hollow mesoporous silica microsphere (HMSM) particles are one of the most promising vehicles for efficient drug delivery owing to their large hollow interior cavity for drug loading and the permeable mesoporous shell for controlled drug release. Here, we report an easily controllable aerosol-based approach to produce HMSM particles by continuous spray-drying of colloidal silica nanoparticles and Eudragit/Triton X100 composite (EUT) nanospheres as templates, followed by template removal. Importantly, the internal structure of the hollow cavity and the external morphology and the porosity of the mesoporous shell can be tuned to a certain extent by adjusting the experimental conditions (i.e., silica to EUT mass ratio and particle size of silica nanoparticles) to optimize the drug loading capacity and the controlled-release properties. Then, the application of aerosol-synthesized HMSM particles in controlled drug delivery was investigated by loading amoxicillin as an antibiotic compound with high entrapment efficiency (up to 46%). Furthermore, to improve the biocompatibility of the amoxicillin-loaded HMSM particles, their surfaces were functionalized with poly­(allylamine hydrochloride) and alginate as biocompatible polymers via the layer-by-layer assembly. The resulting particles were evaluated toward Escherichia coli (Gram-negative) bacteria and indicated the bacterial inhibition up to 90% in less than 2 h. Finally, we explored the versatility of HMSMs as drug carriers for pancreatic cancer treatment. Because the pH value of the extracellular medium in pancreatic tumors is lower than that of the healthy tissue, chitosan as a pH-sensitive gatekeeper was grafted to the HMSM surface and then loaded with a pro-apoptotic NCL antagonist agent (N6L) as an anticancer drug. The obtained particles exhibited pH-responsive drug releases and excellent anticancer activities with inhibition of cancer cell growth up to 60%.

Spray‐Dried TiO2(B)‐Containing Photocatalytic Glass‐Ceramic Nanobeads

“…The selected molar composition (0.83 SiO 2 · 0.17 TiO 2 ) exhibits high liquidus temperature and a strong tendency to crystallize, [ 18 ] which are known to prevent the production of SiO 2 –TiO 2 glasses by the conventional melt‐quench route. [ 19 ] The sample was therefore synthesized by the spray‐drying method, mostly employed for food, [ 20 ] drug delivery systems [ 21,22 ] or ceramic nanoparticles [ 23 ] processing and only limitedly explored for the development of functional glassy and glass‐ceramic materials. [ 24–28 ] On the whole, we additionally report a novel inexpensive method for the production of photocatalytic glass‐ceramic nanobeads based on the crystallization of TiO 2 (B) and anatase.…”

Obtención, funcionalización y aplicaciones biomédicas de las Nanopartículas de Sílice Mesoporosa: una revisión

“…Poostforooshan et al [9], modificaron químicamente la superficie de las MSN a través de dos estrategias, la primera utiliza interacciones electrostáticas, a través del proceso capa por capa (LbL) con polímeros de Poliamida y Alginato para formar diferentes números de capas de polielectrolitos, la segunda implica la formación de enlaces covalentes a través del injerto de quitosano. La técnica de LbL, fue reportada en otro estudio por Hu et al [37] donde se usaron MSN para su uso en entrega de fármaco.…”

“…En otro estudio, Poostforooshan et al [9] investigaron la aplicación de partículas de Microesferas huecas de sílice mesoporosa sintetizadas en aerosol en la administración controlada de fármacos mediante la carga de amoxicilina como un compuesto antibiótico con alta eficiencia de atrapamiento (hasta 46%). Las partículas cargadas con amoxicilina funcionalizadas se evaluaron con bacterias E. Coli e indicaron la inhibición bacteriana hasta el 90% en menos de 2 h.…”

“…Las MSN presentan ventajas sobresalientes, como facilidad de síntesis, alta biocompatibilidad de área específica, alta fase vítrea residual, valores de dureza mejorados, propiedades mecánicas robustas, composición química relativamente inerte [3], alta estabilidad frente a la degradación enzimática [9], alta capacidad de carga [10], biodegradabilidad mejorada [7], gran área de superficie (> 1000 2 / ) [1,11] y grandes volúmenes de poros adaptables (1.3-50 nm) [12]. Además, tienen la capacidad de funcionalizarse con diferentes materiales y/o moléculas a través de la ingeniería de superficies, por lo que se emplean en diferentes ámbitos incluido el de la salud [3].…”

“…Esta funcionalidad ha demostrado ser especialmente beneficiosa en el suministro de fármacos y ha despertado el interés científico por estudiar posibles aplicaciones de las MSN en ingeniería biomédica y nanomedicina. La estructura porosa de las MSN se puede utilizar para cargar moléculas terapéuticas bioactivas permitiendo mejorar varias características farmacológicas de los medicamentos libres, aumentando su eficacia terapéutica [9] y reduciendo los efectos secundarios adversos [13].…”