siRNA delivery to macrophages using aspherical, nanostructured microparticles as delivery system for pulmonary administration

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

“…An established method for this is the layer-by-layer technique [23]. This allows not only the surface to be loaded with drugs, but also polymers to be used as stabilizers for the formation of larger particle constructs [24,25]. This property can be used to manufacture drug delivery systems for pulmonary application, where an aerodynamic diameter of 1-5 µm must be achieved to reach the deep lungs [26].…”

“…In addition, the specific surface area of cylindrical microparticles is significantly larger than the surface area of their spherical counterparts, which allows higher loading quantities. This drug delivery system has already shown that loading with a specific siRNA sequence against TNF-α is possible and a significant reduction in this cytokine release from macrophages could be achieved, but also showed the need for improvement [24].…”

Copaiba Oil-Loaded Polymeric Nanocapsules: Production and In Vitro Biosafety Evaluation on Lung Cells as a Pre-Formulation Step to Produce Phytotherapeutic Medicine

“…Nonetheless, their drug release is severely limited because of their low inertia, which causes them to be predominantly exhaled from the lungs after inspiration [ 43 ]. Given this issue, some researchers frequently report that trojan microparticles, characterized by geometric sizes larger than 3 μm, when obtained from polymeric nanocapsules, are better suitable for the pulmonary route since they show desirable aerosolization efficiency [ 43 , 44 ]. Accordingly, our work presents itself as a “preformulation step”, once the next phases of the study are conducted by our research group to obtain a promising solid phytotherapeutic medicine composed of trojan microparticles.…”

Progress in non-viral localized delivery of siRNA therapeutics for pulmonary diseases

“…Lipidoid-polymer complex 2. Amorphous silica microparticles In vitro Optimal lipidoid: siRNA ratio identified & sustained release siRNA observed but with only moderate TNF- α silencing 112 , 113 Acute lung injury ICAM-1 Exosome encapsulation Intratracheal Disrupted PMN cells adhesion upon LPS stimulation 114 MyD88 Exosome encapsulation Intratracheal Exclusive uptake by activated macrophages and effectively reduced immune cells infiltration 115 PAI-1 Nanoemulsion system functionalized by CXCR4 antagonist Intratracheal Anti-fibrotic effects observed with reduced collagen deposition and cell infiltration in BAL 116 PD-L1 Naked siRNA for intratracheal and liposome-delivery for IV Intratracheal & IV Identified endothelial cells' role in PD-L1 secretion; IV delivery alleviated lung edema and neutrophil influx 117 RIP2 Naked siRNA Intratracheal Suppressed cigarette smoke-induced inflammation and oxidative damage 118 S1PLyase Amphiphilic micelles also functionalized with HMGB1 antagonistic peptides Intratracheal The micellar complex reduced IL-6 significantly better than peptide or siRNA alone while exhibiting high intracellular uptake 119 TNF-α 1. Fluorinated and guanidine bifunctional polypeptide-siRNA complex 2.…”