Applying I-Optimal Design for Tuning Internal Cavity of Hollow Mesoporous Silica Nanoparticles for 5-Fluorouracil Delivery: Investigating Drug-Loading/Releasing Behavior and Biocompatibility Properties

Hollow mesoporous silica nanoparticles (HMSNs) are promising drug carriers due to their large surface area, high porosity, and biocompatibility. In this study, a straightforward and adjustable synthesis strategy was developed for generating HMSNs with tunable hollow cavities and use them to deliver 5-fluorouracil, a common anticancer drug as model drug. This approach involves using solid SiO2 nanoparticles (sSiO2 NPs) and cetyltrimethylammonium bromide (CTAB) as templates. Remarkably, our study introduces the application of I-optimal design to optimize the size of sSiO2 NPs, subsequently impacting the internal cavity diameter and drug loading capacity of the resulting HMSNs. Dynamic light scattering (DLS), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Brunauer Emmett-Teller (BET) analysis, Fourier-transform infrared (FTIR) spectroscopy and in vitro drug release were conducted to characterize the synthesized particles. Moreover, the blood compatibility and cytotoxicity were performed to demonstrate the biocompatibility of as-synthesized HMSNs. Notably, the investigation unveils that both the internal cavity size and shell thickness have discernible effects on drug loading and release behavior. Furthermore, it was observed that HMSNs particle size played a significant role in their hemocompatibility, while confirming that all synthesized HMSNs exhibited appropriate biocompatibility. Overall, these findings highlight the facile control and manipulation of drug loading and release characteristics within HMSNs through tuning the hollow cores. Additionally, these results demonstrate the potential for regulating hemocompatibility, thereby expanding the range of applications for these nanoparticles. This research provides an innovative and versatile methodology for the synthesis of HMSNs, emphasizing their potential application in drug delivery systems.