Aspherical, Nano-Structured Drug Delivery System with Tunable Release and Clearance for Pulmonary Applications.

Addressing the challenge of efficient drug delivery to the lungs, a nano-structured, microparticulate carrier system with defined and customizable dimensions has been developed. Utilizing a template-assisted approach and capillary forces, particles were rapidly loaded and stabilized. The system employs a biocompatible alginate gel as a stabilizing matrix, facilitating the breakdown of the carrier in body fluids with the subsequent release of its nano-load, while also mitigating long-term accumulation in the lung.

Nanostructured Microparticles Repolarize Macrophages and Induce Cell Death in an In Vitro Model of Tumour-Associated Macrophages.

Macrophages (MΦs) in their pro-inflammatory state (M1) suppress tumour growth, while tumour-associated MΦs (TAMs) can promote tumour progression. The aim of this study was to test the hypothesis that targeted delivery of the immune activator poly(I:C) in aspherical silica microrods (µRs) can repolarize TAMs into M1-like cells. µRs (10 µm × 3 µm) were manufactured from silica nanoparticles and stabilized with dextran sulphate and polyethyleneimine.

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.

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.

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

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.

Mechanical properties of gelatin nanoparticles in dependency of crosslinking time and storage.

Mechanical properties of nanoparticles are an important characteristic for drug delivery and therefore, they have gained interest in pharmaceutical research during the last years. Among others, cellular uptake, blood circulation time and accumulation in organs are influenced by the elastic modulus of nanoparticles. Thus, by varying the stiffness of nanoparticles a more specific drug targeting might be achieved.

Silica nanoparticles of microrods enter lung epithelial cells.

A novel type of microparticle has recently been engineered. It consists of amorphous silica nanoparticles and has a corncob-like shape. It has already been demonstrated that alveolar macrophages in the lung are able to engulf this particulate carrier and that it also functions successfully as a gene delivery system.