The development of clinically acceptable albumin-based nanoparticle formulations for use in pulmonary drug delivery has been hindered by concerns about the toxicity of nanomaterials in the lungs combined with a lack of information on albumin nanoparticle clearance kinetics and biodistribution. In this study, the in vivo biocompatibility of albumin nanoparticles was investigated following a single administration of 2, 20, and 390μg/mouse, showing no inflammatory response (TNF-α and IL-6, cellular infiltration and protein concentration) compared to vehicle controls at the two lower doses, but elevated mononucleocytes and a mild inflammatory effect at the highest dose tested. The biodistribution and clearance of (111)In labelled albumin solution and nanoparticles over 48h following a single pulmonary administration to mice was investigated by single photon emission computed tomography and X-ray computed tomography imaging and terminal biodistribution studies. (111)In labelled albumin nanoparticles were cleared more slowly from the mouse lung than (111)In albumin solution (64.1±8.5% vs 40.6±3.3% at t=48h, respectively), with significantly higher (P24h indicating that small amounts of activity were cleared from the lungs both by translocation across the lung mucosal barrier, as well as mucociliary clearance. This study provides important information on the fate of albumin vehicles in the lungs, which may be used to direct future formulation design of inhaled nanomedicines.

In this review, the role of conjugated polymer nanoparticles (CPNs) in emerging bioimaging techniques is described.

The near-infrared absorbing conjugated polymer poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b′]-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT) has been investigated as a contrast agent for optical and photoacoustic imaging. Lipophilic π-conjugated polymers can be efficiently encapsulated within self-assembling diblock copolymer poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG–PLGA) nanoparticles, although the effect of variations in PEG and PLGA chain lengths on nanoparticle properties, performance and biocompatibility have not yet been investigated. In this study, PEG–PLGA with different block lengths (PEG_2kDa–PLGA_4kDa, PEG_2kDa–PLGA_15kDa and PEG_5kDa–PLGA_55kDa) were used to encapsulate PCPDTBT. Nanoparticle sizes were smallest (<100 nm) when using PEG_2kDa–PLGA_4kDa, with <5% PCPDTBT content and a reduction in the total solids concentration of the organic phase. All PEG–PLGA nanoparticles were colloidally stable in water and serum-supplemented cell culture medium over 24 h at 37 °C, with slight evidence of protein surface adsorption. PEG_2kDa–PLGA_4kDa systems showed a threefold lower cytotoxicity (IC₅₀ value) than the other two systems. Haemolytic activity was <2.5% for all systems and no platelet aggregation or inhibition of ADP-induced platelet aggregation was observed. Encapsulation of PCPDTBT within a PEG–PLGA matrix shifted fluorescence emission towards red wavelengths (760 nm in THF vs. 840 nm in nanoparticles) and reduced the quantum yield by 30–70-fold compared to THF. Nonetheless, PCPDTBT:PEG_2kDa–PLGA_4kDa systems had a marginally higher quantum yield and signal-to-background ratio in a phantom mouse compared with PEG_2kDa–PLGA_15kDa and PEG_5kDa–PLGA_55kDa systems. As a photoacoustic imaging probe, PCPDTBT:PEG_2kDa–PLGA_4kDa systems also showed a higher photoacoustic amplitude compared to higher molecular weight PEG–PLGA systems. Overall, the low molecular weight PEG_2kDa–PLGA_4kDa nanoparticle systems conferred the benefits of smaller sizes, reduced cytotoxicity and enhanced imaging performance compared to higher molecular weight matrix polymers.