Nanostructured Porous Silicon‐Solid Lipid Nanocomposite: Towards Enhanced Cytocompatibility and Stability,Reduced Cellular Association,and Prolonged Drug Release

A major bottleneck in nanometer‐scale drug delivery systems is the fabrication of nanocarriers with excellent stability under physiological conditions that can both efficiently encapsulate therapeutic agents and controllably release their payloads. Herein, the formation of a novel nanocomposite based on the encapsulation of thermally hydrocarbonized porous silicon (THCPSi) nanoparticles with solid lipid nanoparticles (SLNs) on a 1:1 ratio is described. The THCPSi‐SL nanocomposites (THCPSi‐SLNCs) are formed using a solid‐in‐oil‐in‐water emulsion solvent evaporation method. TEM and FTIR analyses prove that THCPSi nanoparticles are successfully encapsulated in the SLN matrix. The formation of the THCPSi‐SLNCs alters the surface smoothness and hydrophobicity of the THCPSi nanoparticles, and also remarkably enhances their stability in human plasma. After encapsulation, the cytocompatibility of the THCPSi nanoparticles with intestinal, liver, and macrophage cancer cells is also greatly improved. A prolonged release of the model drug, furosemide, from THCPSi‐SLNC is achieved, indicating that the SLN matrix successfully seals the pores of the THCPSi nanoparticles. Flow cytometry and confocal fluorescence microscopy studies demonstrates the significantly reduced cellular association of THCPSi‐SLNCs with the cells comparing to bare THCPSi nanoparticles. Overall, the THCPSi‐SLNCs exhibits superior suspensibility and better stability against aggregation in aqueous buffer solutions, increases the particle surface smoothness and cytocompatibility, reduces the cellular association, increases the in vitro stability in human plasma, and prolonges the drug release. These results suggest that the nanocomposite is a promising nanovector system for drug delivery applications.