N,N,N-Trimethyl chitosan as a permeation enhancer for inhalation drug delivery: Interaction with a model pulmonary surfactant

Szabová, Jana; Mravec, Filip; Mokhtari, Mostafa; Borgne, Rémi Le; Kalina, Michal; Berret, Jean‐François

doi:10.1016/j.ijbiomac.2023.124235

Cited by 3 publications

(1 citation statement)

References 75 publications

(129 reference statements)

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“…Interestingly, PxB molecules mediated “close mutual contact” of EPS bilayers even if they constitute ULV that are diluted enough to avoid any interaction between particles (1 wt % of the lipid). This finding correlates well with the concept that PxB mimics the properties of SP-B protein and the formation of stable vesicle–vesicle contacts allowing the exchange of phospholipids. , A similar “condensing” effect was recently reported for the interaction of cationic nanoparticles and polymers with PSUR, , cationic liposomes with polyelectrolytes of opposite charges, such as DNA, − or in the context of antimicrobial mechanisms of cationic peptides that interact with bacterial model membranes . However, it is worth stressing two points: (1) our experiments show that binding of PxB molecules onto EPS bilayers results in charge inversion of the membrane, as shown by the zeta potential and proved by SANS measurements.…”

Section: Resultssupporting

confidence: 90%

Polymyxin B-Enriched Exogenous Lung Surfactant: Thermodynamics and Structure

Královič-Kanjaková,

Asi Shirazi,

Hubčík

et al. 2024

Langmuir

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The use of an exogenous pulmonary surfactant (EPS) to deliver other relevant drugs to the lungs is a promising strategy for combined therapy. We evaluated the interaction of polymyxin B (PxB) with a clinically used EPS, the poractant alfa Curosurf (PSUR). The effect of PxB on the protein-free model system (MS) composed of four phospholipids (diC16:0PC/16:0–18:1PC/16:0–18:2PC/16:0–18:1PG) was examined in parallel to distinguish the specificity of the composition of PSUR. We used several experimental techniques (differential scanning calorimetry, small- and wide-angle X-ray scattering, small-angle neutron scattering, fluorescence spectroscopy, and electrophoretic light scattering) to characterize the binding of PxB to both EPS. Electrostatic interactions PxB–EPS are dominant. The results obtained support the concept of cationic PxB molecules lying on the surface of the PSUR bilayer, strengthening the multilamellar structure of PSUR as derived from SAXS and SANS. A protein-free MS mimics a natural EPS well but was found to be less resistant to penetration of PxB into the lipid bilayer. PxB does not affect the gel-to-fluid phase transition temperature, T m, of PSUR, while T m increased by ∼+ 2 °C in MS. The decrease of the thickness of the lipid bilayer (d L) of PSUR upon PxB binding is negligible. The hydrophobic tail of the PxB molecule does not penetrate the bilayer as derived from SANS data analysis and changes in lateral pressure monitored by excimer fluorescence at two depths of the hydrophobic region of the bilayer. Changes in d L of protein-free MS show a biphasic dependence on the adsorbed amount of PxB with a minimum close to the point of electroneutrality of the mixture. Our results do not discourage the concept of a combined treatment with PxB-enriched Curosurf. However, the amount of PxB must be carefully assessed (less than 5 wt % relative to the mass of the surfactant) to avoid inversion of the surface charge of the membrane.

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Section: Resultssupporting

confidence: 90%

Polymyxin B-Enriched Exogenous Lung Surfactant: Thermodynamics and Structure

Královič-Kanjaková,

Asi Shirazi,

Hubčík

et al. 2024

Langmuir

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Advances in Pulmonary Protein Delivery Systems

Zhao,

Liu,

2024

Advanced NanoBiomed Research

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Protein‐based therapeutics and vaccines play a pivotal role in the realm of biomedical science. Pulmonary administration offers several advantages including rapid adsorption, non‐invasive, increased local drug concentration, and bypassed first‐pass metabolism, thus holding great potential to address multiple unmet medical needs in lung‐related diseases and vaccination. However, the limited success of inhaled proteins in clinical settings highlights the challenges associated with protein stability and the physiological barriers within the respiratory system. To overcome these hurdles, a variety of delivery systems including polymers, liposomes, cell‐derived membranes, and inorganic materials are developed to improve the stability, mucus penetration, retention time, and bioavailability of proteins. With the outbreak of COVID‐19, the pulmonary administration of proteins has drawn great attention. In this review, the design principle, preparation, biomedical application, progress in clinical translation, advantages, and disadvantages of each kind of delivery system are summarized, with an emphasis on carrier materials.

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