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

siRNA delivery to macrophages using aspherical, nanostructured microparticles as delivery system for pulmonary administration. Eur J Pharm Biopharm. 2020 Dec 04;: Authors: Fischer T, Tschernig T, Drews F, Brix K, Meier C, Simon M, Kautenburger R, Schneider M Abstract The delivery of oligonucleotides such as siRNA to the lung is a major challenge, as this group of drugs has difficulties to overcome biological barriers due to its polyanionic character and the associated hydrophilic properties, resulting in inefficient delivery. Especially in diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis, where increased proinflammation is present, a targeted RNA therapy is desirable due to the high potency of these oligonucleotides. To address these problems and to ensure efficient uptake of siRNA in macrophages, a microparticulate, cylindrical delivery system was developed. In the first step, this particle system was tested for its aerodynamic characteristics to evaluate the aerodynamic properties to optimize lung deposition. The mass median aerodynamic diameter of 2.52 ± 0.23µm, indicates that the desired target should be reached. The inhibition of TNF-α release, as one of the main mediators of proinflammatory reactions, was investigated. We could show that our carrier system can be loaded with siRNA against TNF-α. Gel electrophoreses allowed to demonstrate that the load can be incorporated and released withou...
Source: European Journal of Pharmaceutics and Biopharmaceutics - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Biopharm Source Type: research