Enhancing nanoparticle penetration through airway mucus to improve drug delivery efficacy in the lung

A Two‐Pronged Pulmonary Gene Delivery Strategy: A Surface‐Modified Fullerene Nanoparticle and a Hypotonic Vehicle

“… [20] These pathological features essentially reinforce biological delivery barriers to inhaled gene transfer to lung epithelial cells in both airways and airspace. [5a] Nevertheless, pZG/TPFE‐PEG provided remarkably widespread transgene expression (≈35 % coverage) in the lungs of Scnn1b ‐Tg mice (Figure 3 A,D ), although the coverage was reduced compared to what we observed in in healthy mouse lungs (Figure 3 B ). We also found that pGL3/TPFE‐PEG retained the ability to mediate high‐level overall transgene expression in the lungs of Scnn1b ‐Tg mice regardless of the more challenging delivery barriers (Figure 3 E ).…”

“…However, while non‐PEGylated nanoparticles, including pZG/TPFE and pGL3/TPFE, exhibited highly positive ζ‐potential values (>25 mV), PEGylated nanoparticles, including pZG/TPFE‐PEG and pGL3/TPFE‐PEG, possessed near‐neutral surface charges (<3.5 mV) (Table S1), suggesting that the otherwise positively charged particle surfaces were efficiently shielded by PEG. It is critical to retain desired particle properties in physiologically relevant conditions for in vivo application, [5a] and thus we assessed colloidal stability of pZG/TPFE and pZG/TPFE‐PEG in mouse bronchoalveolar lavage fluid (BALF). The size and polydispersity index (PDI) of pZG/TPFE increased instantaneously upon incubation in BALF, whereas pZG/TPFE‐PEG exhibited excellent colloidal stability, as evidenced by unperturbed size and PDI at least up to 5 hours (Figure 1 F ).…”

A Two‐Pronged Pulmonary Gene Delivery Strategy: A Surface‐Modified Fullerene Nanoparticle and a Hypotonic Vehicle

“…Scnn1b ‐Tg mice exhibit key pathologies of CF and COPD, including mucus accumulation/stasis and chronic lung inflammation [20] . These pathological features essentially reinforce biological delivery barriers to inhaled gene transfer to lung epithelial cells in both airways and airspace [5a] . Nevertheless, pZG/TPFE‐PEG provided remarkably widespread transgene expression (≈35 % coverage) in the lungs of Scnn1b ‐Tg mice (Figure 3 A,D), although the coverage was reduced compared to what we observed in in healthy mouse lungs (Figure 3 B).…”

Nanostructures for drug delivery in respiratory diseases therapeutics: Revision of current trends and its comparative analysis

“…Also, the presence of mucus in the respiratory tract has an important role in lung drug delivery. Nanoparticles with a size greater than 200 nm will be trapped by the glycoprotein network that conforms to the mucus [ 200 ]. In addition to particle size, the surface charge of the DDS will define if the particles interact with the mucus barrier, in this sense, it has been shown that neutral DDS has better diffusion into the mucus layer [ 201 ].…”