Nebulised lipid-polymer hybrid nanoparticles for the delivery of a therapeutic anti-inflammatory microRNA to bronchial epithelial cells.

Modulation of microRNAs (miRNAs), endogenous regulators of gene expression, is a promising strategy for tackling inflammatory lung diseases. In this proof-of-concept study, we tested delivery of miR-17 to bronchial epithelial cells (BECs) using nebulised lipid-polymer hybrid nanoparticles (LPNs). The primary aim was to reduce the induced secretion of miR-17's target, the pro-inflammatory chemokine interleukin (IL)-8.

Modified Vaccinia Virus Ankara Preferentially Targets Antigen Presenting Cells In Vitro, Ex Vivo and In Vivo.

Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP).

Optimization and Dose Estimation of Aerosol Delivery to Non-Human Primates.

Background: In pre-clinical animal studies, the uniformity of dosing across subjects and routes of administration is a crucial requirement. In preparation for a study in which aerosolized live-attenuated measles virus vaccine was administered to cynomolgus monkeys (Macaca fascicularis) by inhalation, we assessed the percentage of a nebulized dose inhaled under varying conditions.

Methods: Drug delivery varies with breathing parameters.

Aerosol-mediated delivery of AAV2/6-IκBα attenuates lipopolysaccharide-induced acute lung injury in rats.

Inhibition of the proinflammatory transcription factor NF-κB has previously been shown to attenuate the inflammatory response in tissue after injury. However, the feasibility and efficacy of aerosolized adeno-associated viral (AAV) vector-delivered transgenes to inhibit the NF-κB pathway are less clear. Initial studies optimized the AAV vector for delivery of transgenes to the pulmonary epithelium.

Optimized aerosol delivery to a mechanically ventilated rodent.

Background: Aerosol delivery through an endotracheal tube during mechanical ventilation of small animals, simulating neonates and small infants, has shown to be influenced by a variety of factors including aerosol generator type, droplet/particle size, ventilator circuitry and ventilation regime. A review of the literature indicates that reported aerosol deposition rates in rodents are quite low, with lung deposition in anesthetized, mechanically ventilated rats reported to be approximately 3.9 and approximately 8% in anesthetized, spontaneously breathing rats.