Biology subjects

Wang, J.-l.

Publications and source records attributed to Wang, J.-l..

2 recordsLinked to original sources

bioRxiv2022

Aerosolizable plasmid DNA dry powders engineered by thin-film freezing

This study was designed to test the feasibility of using thin-film freezing (TFF) to prepare aerosolizable dry powders of plasmid DNA (pDNA) for pulmonary delivery. Dry powders of pDNA formulated with mannitol/leucine (70/30, w/w) at various of drug loadings, solid contents, and solvents were prepared using TFF, their aerosol properties (i.e., mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF)) determined, and selected powders were used for further characterization. Of the nine dry powders prepared, their MMAD values were about 1-2 mm, with FPF values (delivered) of 40-80%. The aerosol properties of the powders were inversely correlated with the pDNA loading and the solid content in the pDNA solution before thin-film freezing. Powders prepared with Tris-EDTA (TE) buffer or cosolvents (i.e., 1,4 dioxane or t-butanol in water), instead of water, showed slightly reduced aerosol properties. Ultimately, powders prepared with pDNA loading at 5% (w/w), 0.25% of solid content, with or without TE were selected for further characterization due to their overall good aerosol performance. The pDNA powders exhibited a porous matrix, crystalline structure, with a moisture content of <2% (w/w). Agarose gel electrophoresis confirmed the chemical integrity of the pDNA after it was subjected to TFF and after the TFF powder was actuated. A cell transfection study confirmed the activity of the pDNA after it was subjected to TFF. In conclusion, it is feasible to use TFF to produce aerosolizable pDNA dry powder for pulmonary delivery, while preserving the integrity and activity of the pDNA.

pharmacology and toxicology↗

bioRxiv2020

Autophagy-associated Production of Antimicrobial Peptides hBD1 and LL37 Exhibits Anti-Bacillus Calmette-Guerin Effects in Lung Epithelial Cells.

Antimicrobial peptides (AMPs) constitute important groups of bactericidal polypeptides against various microorganisms that exhibit their anti-bacteria activity through cleavage of precursor peptides into the active form of 50-100 amino acids in length. Various AMP cleavage mechanisms have been reported in different cell types; however, those in Mycobacterium tuberculosis (MTB)-infected lung epithelial cells remain unknown. In the present study, we found that MTB-infected lung epithelial cells expressed high level of the AMPs hBD1 and LL37 to kill intracellular MTB as the first-line immune barrier against MTB infection. Notably, their production in the lung epithelial cells was closely related to the function of autophagosomes and lysosomes. Experimental induction of autophagy in lung epithelial cells could enhance the expression of active hBD1 and LL37 at the post-transcriptional level, whereas silencing of these two active AMPs could decrease the bactericidal effect of autophagy. These findings indicated that cleavage of peptide precursors to form active AMPs might constitute a previously unrecognized antibacterial mechanism of autophagy. Author summaryLM and RW conceived and designed the experiments; RW performed the experiments and analyzed the data; QW analyzed the data and contributed reagents/materials/analysis tools; HL performed the experiments; XZ, JY, YL and ZH analyzed the data. LM and RW drafted the manuscript.

immunology↗