Mucus penetrating properties of soft, distensible lipid nanocapsules

Designing nanomaterials to release their drug pay-load upon exposure to an exogenous trigger can help to direct drug delivery, but how the triggered release, which often modifies the nanomaterial properties, influences the biological fate of these systems is currently unknown. The aim of this study was to investigate how the triggered drug release from PEG coated, soft, 50 nm distensible lipid nanocapsules (LNC) influenced their diffusion across a mucus barrier. The translocation speed of the non-triggered LNC across a 35 µm thick purified gastric mucin (PGM) barrier was 3 times faster (30.08 ± 2.49 x 10-10 cm2 s-1) compared to equivalent-sized negatively charged polystyrene particles (9.87 ± 0.61 x 10-10 cm2 s-1, p 0.05) in a static mucus barrier, but when shear was applied to the barrier the distended LNCs diffused more slowly (3.97 ± 1.38 x 10-8 cm2s-1, p < 0.05) compared to the non-distended materials (4.94 ± 0.04 x 10-8 cm2s-1). This data suggested the rapid mucus penetration of the distended LNCs, despite their increased size, was a consequence of their capacity to take a less tortious path through the barrier, i.e., they experienced less steric hinderance, compared to the non-distended LNC

Antimicrobial molecules in the lung:formulation challenges and future directions for innovation

Inhaled antimicrobials have been extremely beneficial in treating respiratory infections, particularly chronic infections in a lung with cystic fibrosis. The pulmonary delivery of antibiotics has been demonstrated to improve treatment efficacy, reduce systemic side effects and, critically, reduce drug exposure to commensal bacteria compared with systemic administration, reducing selective pressure for antimicrobial resistance. This review will explore the specific challenges of pulmonary delivery of a number of differing antimicrobial molecules, and the formulation and technological approaches that have been used to overcome these difficulties. It will also explore the future challenges being faced in the development of inhaled products and respiratory infection treatment, and identify future directions of innovation, with a particular focus on respiratory infections caused by multiple drug-resistant pathogens. </jats:p

Surface chemistry of photoluminescent F8BT conjugated polymer nanoparticles determines protein corona formation and internalization by phagocytic cells

Conjugated polymer nanoparticles are being developed for a variety of diagnostic and theranostic applications. The conjugated polymer, F8BT, a polyfluorene derivative, was used as a model system to examine the biological behavior of conjugated polymer nanoparticle formulations stabilized with ionic (sodium dodecyl sulfate; F8BT-SDS; ∼207 nm; −31 mV) and nonionic (pegylated 12-hydroxystearate; F8BT-PEG; ∼175 nm; −5 mV) surfactants, and compared with polystyrene nanoparticles of a similar size (PS200; ∼217 nm; −40 mV). F8BT nanoparticles were as hydrophobic as PS200 (hydrophobic interaction chromatography index value: 0.96) and showed evidence of protein corona formation after incubation with serum-containing medium; however, unlike polystyrene, F8BT nanoparticles did not enrich specific proteins onto the nanoparticle surface. J774A.1 macrophage cells internalized approximately ∼20% and ∼60% of the F8BT-SDS and PS200 delivered dose (calculated by the ISDD model) in serum-supplemented and serum-free conditions, respectively, while cell association of F8BT-PEG was minimal (<5% of the delivered dose). F8BT-PEG, however, was more cytotoxic (IC₅₀ 4.5 μg cm^–2) than F8BT-SDS or PS200. The study results highlight that F8BT surface chemistry influences the composition of the protein corona, while the properties of the conjugated polymer nanoparticle surfactant stabilizer used determine particle internalization and biocompatibility profile