Cylindrical Microparticles Composed of Mesoporous Silica Nanoparticles for the Targeted Delivery of a Small Molecule and a Macromolecular Drug to the Lungs: Exemplified with Curcumin and siRNA

Abstract

The transport of macromolecular drugs such as oligonucleotides into the lungs has become increasingly relevant in recent years due to their high potency. However, the chemical structure of this group of drugs poses a hurdle to their delivery, caused by the negative charge, membrane impermeability and instability. For example, siRNA to reduce tumour necrosis factor alpha (TNF-α) secretion to reduce inflammatory signals has been successfully delivered by inhalation. In order to increase the effect of the treatment, a co-transport of another anti-inflammatory ingredient was applied. Combining curcumin-loaded mesoporous silica nanoparticles in nanostructured cylindrical microparticles stabilized by the layer-by-layer technique using polyanionic siRNA against TNF-α was used for demonstration. This system showed aerodynamic properties suited for lung deposition (mass median aerodynamic diameter of 2.85 ± 0.44 µm). Furthermore, these inhalable carriers showed no acute in vitro toxicity tested in both alveolar epithelial cells and macrophages up to 48 h incubation. Ultimately, TNF-α release was significantly reduced by the particles, showing an improved activity co-delivering both drugs using such a drug-delivery system for specific inhibition of TNF-α in the lungs.

Recent Advances in Nanoparticle-Mediated Co-Delivery System: A Promising Strategy in Medical and Agricultural Field

“…Although many effective research studies and treatments have been made, nucleic acids face the same problems with cancer heterogeneity and adaptive resistance as traditional small molecule drugs in cancer therapy. With the achievements obtained from the fields of chemotherapy and gene therapy, co-delivery of drugs and genes has attracted wide attention in combination therapy due to its synergistic therapeutic effects [ 71 , 72 , 73 ]. The general incentive behind the co-delivery system is to disrupt MDR signaling pathways.…”

Curcumin-loaded mesoporous silica nanoparticles for drug delivery: synthesis, biological assays and therapeutic potential – a review

“…The co-delivery of Cur with siRNA encapsulated into the MSNs signicantly inhibited the TNF-a release when compared to free Cur and siRNA, indicating that it might be a promising dual-drug delivery platform for lowering macrophage inammatory responses in the lungs. 81 Lojkowski et al designed and synthesized phosphonatefunctionalized MSNs using (3-(trihydroxysilyl) propyl methylphosphonate monosodium to improve the loading content of Cur and colchicine. Aer the synthesis of phosphonate-functionalized MSNs, Cur and colchicine or their combination were loaded on MSNs and then the core-shell structure was completed by coating with folic acid conjugated with chitosan-cellulose polymer.…”

Mesoporous silicas in materials engineering: Nanodevices for bionanotechnologies

“…Cylindrical nanoparticles have emerged, instead, as appealing tools for lung application since they hold aerodynamic parameters suitable for inhalation and the ability to delay macrophage uptake and, consequently, allow a sustained residence time of the formulation in the lungs. This type of MSNs has been used by Schneider and co-workers [ 63 ] to deliver curcumin and a specific siRNA to reduce tumor necrosis factor alpha (TNF-α) secretion in the inflammatory process. A significant inhibition effect was observed by the authors depicting the potential for future applications of such carrier system in the treatment of diseases in which macrophages play central roles in inflammation (e.g., COVID-19) or even bacterial infections such as tuberculosis.…”