Pulmonary Inhaled Nanocarriers Improve Pharmacokinetics of Drug Delivery to the Distal Lung for Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease that causes progressive decline in lung function as lung tissue becomes replaced by scar tissue. IPF has significant morbidity, exhibited by shortness of breath and oxygen dependence, and an average survival of only 5 years following diagnosis. The current standard of care is to treat IPF patients with anti-fibrotic drugs that slow the rate of declining lung function but do not reduce symptoms or prolong life. Additionally, these drugs have significant side effects that often necessitate dose reduction or limit patients’ ability to take them at all. To improve the pharmacokinetics of the anti-fibrotic drug nintedanib, we utilize two methods, nano-scale drug carriers and inhaled delivery directly to the lungs. Combined, these techniques are referred to as Pulmonary Inhaled Nanocarreirs (PINs). PINs deliver 8000x more nintedanib to the lung and have a 10x longer lung half-life compared to conventional oral drug delivery in a murine model. Further, PINs reach multiple cell types in the distal lung, retain their shape after exposure to murine surfactant, and have no demonstrable toxicity. Ultimately we hypothesize that the improved pharmacokinetics attained with PINs will enable better efficacy and reduced side effects in the treatment of IPF and other diseases of the distal lung. </p

Exciton–Phonon Coupling and Low Energy Emission in 2D and Quasi-2D BA₂MA_<i>n</i>–1Pb_<i>n</i>I_3<i>n</i>+1 Thin Films with Improved Phase Purity

Phonon scattering with photogenerated excitons and free charges greatly affects optoelectronic properties of metal halide perovskites and governs their emission line width. Benefiting from the improved phase purity, we are able to analyze exciton–phonon coupling in 2D and quasi-2D BA2MAn–1PbnI3n+1 (n = 1–3) thin films using temperature-dependent photoluminescence (PL) spectroscopy. The layer thickness (n value) dependent coupling of free excitons with both acoustic and longitudinal optical (LO) phonons was extracted quantitatively by fitting the temperature-dependent PL line width and band gap. The low energy emissive signatures below free excitons at low temperature might belong to the emission of self-trapped excitons and bounded excitons in structural defects. Our findings provide a systematic picture for the layer thickness (n value) dependent exciton–phonon coupling in 2D and quasi-2D perovskite thin films and could be helpful for improving the optoelectronic performance of devices made by Ruddlesden–Popper perovskite thin films

Ternary Assemblies of TADF Core/TDBC-J-Aggregate Shell Nanoparticles and d/l‑Phenylalanine-Based Nanohelixes for Circularly Polarized Luminescence

Developing pure organic nanostructures with circularly polarized luminescence (CPL) response is of high interest for the community. As ordered nanoassemblies of a conjugated dye, the J-aggregate exhibits an ultra-narrow emission bandwidth, a high radiative rate, and a largely red-shifted emission but has been rarely employed for constructing a CPL system due to the minimized Stokes shift and the rigorous condition of assembling. In this work, we developed a simple strategy of ternary co-assembling to facilitate narrowband CPL response of cyanine J-aggregates, in which J-aggregate emitters were co-assembled as a shell of light harvester nanoparticles to form the core–shell structures in the nanoscale. Taking advantage of the core–shell energy transfer (FRET) and chiral transfer from assembled nanohelixes to J-aggregate emitters, the narrowband (fwhm <10 nm and centered at ∼585 nm) CPL response of TDBC-J was demonstrated with a dissymmetric factor glum of ±1 × 10–3. Our work provides a simple approach to facilitate narrowband CPL response from J-aggregates in an aqueous solution, which might be able to offer opportunities to achieve CPL response in a greatly red-shifted even near-infrared regime with potential applications

Exciton–Phonon Coupling and Low Energy Emission in 2D and Quasi-2D BA₂MA_<i>n</i>–1Pb_<i>n</i>I_3<i>n</i>+1 Thin Films with Improved Phase Purity

Phonon scattering with photogenerated excitons and free charges greatly affects optoelectronic properties of metal halide perovskites and governs their emission line width. Benefiting from the improved phase purity, we are able to analyze exciton–phonon coupling in 2D and quasi-2D BA2MAn–1PbnI3n+1 (n = 1–3) thin films using temperature-dependent photoluminescence (PL) spectroscopy. The layer thickness (n value) dependent coupling of free excitons with both acoustic and longitudinal optical (LO) phonons was extracted quantitatively by fitting the temperature-dependent PL line width and band gap. The low energy emissive signatures below free excitons at low temperature might belong to the emission of self-trapped excitons and bounded excitons in structural defects. Our findings provide a systematic picture for the layer thickness (n value) dependent exciton–phonon coupling in 2D and quasi-2D perovskite thin films and could be helpful for improving the optoelectronic performance of devices made by Ruddlesden–Popper perovskite thin films

Typical 600 MHz ¹H-NMR spectra of rat plasma samples.

<p>1.Lipids (VLDL/LDL) 3. Isoleucine 4. Valine 5.3-Hydroxybutyrate 6. Lactate 7. Alanine 8. Lysine 9. Arginine 12. N-Acetyl glycoproteins 14. Glutamate 16. Acetoacetate 17. Acetone 18. Succinate 19. Pyruvate 20. Glutamine 21. Citrate 22. Glutathione 23. Aspartate 24. Creatine 26. Choline 27. Phosphocholine/GPC 28. TMAO 30. Glucose/aminoacids resonances 34.α-Glucose 35. Glycogen 37. Fumarate 38. Tyrosine.</p

Summary of the metabolic pathways related to the metabolites that changed significantly in the hyperlipidemia model.

<p>“↑” and “↓” indicate that the compound is up- and down-regulated compared with the control group.</p

PR analysis of ¹H-NMR spectra of rat liver tissues.

<p>(A): PCA analysis of the spectra of liver tissues from normal and hyperlipidemia rats (R²X=0.955, Q²=0.782). (B): Scores plot of the OPLS-DA analysis of the spectra from the liver tissues of normal and hyperlipidemia rats (R²X=0.953, R²Y=0.999, Q²=0.827). (C): Scores plot of the OPLS-DA analysis of the spectra from the liver tissues of normal, hyperlipidemia and GP-treated rats (R²X=0.955, R²Y=0.984, Q²=0.608). (D): Scores plot of the OPLS-DA analysis of the spectra from the liver tissues of normal, hyperlipidemia and Atorvastatin-treated rats (R²X=0.931, R²Y=0.945, Q²=0.544). (E): Loading plot of the OPLS-DA analysis of the spectra from the liver tissues of normal and hyperlipidemia rats. </p

Typical 600 MHz ¹H-NMR spectra of rat liver samples.

<p>1. Lipids (VLDL/LDL) 2. Leucine 3. Isoleucine 4. Valine 5.3-Hydroxybutyrate 6. Lactate 7. Alanine 8. Lysine 9. Arginine 10. Acetate 11. Proline 12. N-Acetyl glycoproteins 13. O-Acetyl glycoproteins 14. Glutamate 15. Methionine 16. Acetoacetate 17. Acetone 18. Succinate 19. Pyruvate 20. Glutamine 21. Citrate 22. Glutathione 23. Aspartate 24. Creatine 25. Phosphatidylcholine 26. Choline 27. Phosphocholine/GPC 28. TMAO 29. Taurine 30. Glucose/aminoacids resonances 31.myo–Inositol 32. Threonine 33. β-Glucose 34.α-Glucose 35. Glycogen 36. Adenosine/Inosine 37. Fumarate 38. Tyrosine 39. Phenylalanine 40. Histidine.</p

PR analysis of the ¹H-NMR spectra of rat plasma.

<p>(A): PCA analysis of the spectra of plasma from normal and hyperlipidemia rats (R²X=0.988, Q²=0.885). (B): Scores plot of the OPLS-DA analysis of the spectra from the plasma of normal and hyperlipidemia rats (R²X=0.925, R²Y=0.874, Q²=0.642). (C): Scores plot of the OPLS-DA analysis of the spectra from the plasma of normal, hyperlipidemia and GP-treated rats (R²X=0.968, R²Y=0.878, Q²=0.538). (D): Scores plot of the OPLS-DA analysis of the spectra from the plasma of normal, hyperlipidemia and Atorvastatin-treated rats (R²X=0.909, R²Y=0.522, Q²=0.328). (E): Loading plot of the OPLS-DA analysis of the spectra from the plasma of normal and hyperlipidemia rats.</p

Tuning Hybridized Local and Charge-Transfer Mixing for Efficient Hot-Exciton Emission with Improved Color Purity

Delayed fluorescence (DF) emitters with high color purity are of high interest for applications in high-resolution displays. However, the charge transfer required by high emitting efficiency usually conflicts with the expected color purity. In this work, we investigated the S1/S0 conformational relaxation, spin–orbital coupling (SOC), and vibronic coupling of hot-exciton emitters while hybrid local and charge transfer (HLCT) state tuning was achieved by a structural meta-effect. The meta-linkage leads to suppressed S1/S0 conformational relaxation and weakened vibronic coupling, while the unsacrificed emitting efficiency is largely ensured by multiple rISC channels (Tn → Sm) with thermally accessible triplet–singlet energy gap (ΔEST) and effective SOC. We demonstrated that the unique excited-state mechanism provides opportunities to improve the emitting color purity of hot-exciton emitters without sacrificing emitting efficiency by HLCT state tuning with simple chemical structural modification, for which hot-exciton emitters might play a more important role for high-resolution organic light-emitting diode displays