Permeation of beta-defensin-3 encapsulated with polyethylene glycol in lung surfactant models at air-water interface

Souza, Felipe Rodrigues de; Souza, Lucas Miguel Pereira; Pimentel, André Silva

doi:10.1016/j.colsurfb.2019.110357

Cited by 17 publications

(10 citation statements)

References 94 publications

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“…The cutoff of 1.2 nm was used for Lennard-Jones (LJ) and for Coulomb interactions. In the production MD simulation, the leapfrog algorithm, Nose–Hoover thermostat, and the Parrinello–Rahman barostat were used as protocols developed in previous studies. − The trajectory was used to create the CG cholesterol models using the pyCGTOOL module . The mapping step involves the identification of groups with about four heavy atoms represented by a bead, which is chosen based on the expected polarity for each group …”

Section: Methodsmentioning

confidence: 99%

Lipophilicity of Coarse-Grained Cholesterol Models

Fornasier

Souza

et al. 2020

J. Chem. Inf. Model.

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The lipophilicity of cholesterol was investigated by using coarse-grained molecular dynamics and umbrella sampling. The previous coarse-grained cholesterol models in the literature are more hydrophobic than our model. The Gibbs free energy of transferring cholesterol from the octanol phase to water phase (ΔG o/w) was 11.88 ± 0.08 kcal mol–1, and the octanol–water partitioning coefficient (logP) was estimated to be 8.72 ± 0.06. The latter is in agreement with the logP values found by bioinformatics, which are standard methods to predict the lipophilicity, giving excellent octanol/water partitioning coefficients compared with experimental ones for different molecules. We also performed the first experimentally direct measurement of this important property for cholesterol. The experimental octanol/water partitioning coefficient of cholesterol was measured to be 8.86 ± 0.79, which is in excellent agreement with our calculated logP value from our parametrized coarse-grained cholesterol model. This shows the significance of systematic optimization of the lipophilicity for developing coarse-grain models of important biomolecules with complicated molecular structures and hydrophobic character like cholesterol.

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Section: Methodsmentioning

confidence: 99%

Lipophilicity of Coarse-Grained Cholesterol Models

Fornasier

Souza

et al. 2020

J. Chem. Inf. Model.

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“…Our group simulated PEGylated magainin 2 and tachyplesin I interacting with lipid bilayers, showing that PEGylation reduces the binding strength between peptides and bilayer surfaces, which occurs more significantly for α-helical magainin 2 than for β-sheet tachyplesin I [81]. Recently, Jafari et al simulated PEG-encapsulated magainin 2 and found that the PEG-peptide interaction is significantly modulated by aromatic and basic residues of the peptide [82], and Souza et al simulated the insertion of PEG-encapsulated human beta-defensin-3 to lung surfactant models, showing that PEG chains promote the translocation of the peptide from gas phase to water phase [83]. Asadzadeh et al simulated GF-17 (17th-32nd residues of LL-37) interacting with chitosan, PEG, or both, showing that the peptide interacts more tightly with PEG than with chitosan ( Figure 3), leading to lower helicity in the presence of PEG [84].…”

Section: Antimicrobial Peptidesmentioning

confidence: 99%

Molecular Simulations of PEGylated Biomolecules, Liposomes, and Nanoparticles for Drug Delivery Applications

Lee

2020

Pharmaceutics

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Since the first polyethylene glycol (PEG)ylated protein was approved by the FDA in 1990, PEGylation has been successfully applied to develop drug delivery systems through experiments, but these experimental results are not always easy to interpret at the atomic level because of the limited resolution of experimental techniques. To determine the optimal size, structure, and density of PEG for drug delivery, the structure and dynamics of PEGylated drug carriers need to be understood close to the atomic scale, as can be done using molecular dynamics simulations, assuming that these simulations can be validated by successful comparisons to experiments. Starting with the development of all-atom and coarse-grained PEG models in 1990s, PEGylated drug carriers have been widely simulated. In particular, recent advances in computer performance and simulation methodologies have allowed for molecular simulations of large complexes of PEGylated drug carriers interacting with other molecules such as anticancer drugs, plasma proteins, membranes, and receptors, which makes it possible to interpret experimental observations at a nearly atomistic resolution, as well as help in the rational design of drug delivery systems for applications in nanomedicine. Here, simulation studies on the following PEGylated drug topics will be reviewed: proteins and peptides, liposomes, and nanoparticles such as dendrimers and carbon nanotubes.

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“…220 In another example, coarse-grained MD was performed to investigate whether PEG encapsulation could be used to enhance pulmonary absorption and permeation of an antimicrobial peptide. 221 Another study used MD for the prediction of carrier behaviour in a polar in vivo condition. 222 These studies used MD to simulate the interactions of excipients and drugs to investigate their potential fate following lung delivery.…”

Section: Model-informed Formulation Development For Inhaled Pharmaceumentioning

confidence: 99%

Contemporary Formulation Development for Inhaled Pharmaceuticals

Sou

Bergström

2021

Journal of Pharmaceutical Sciences

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Pulmonary delivery has gained increased interests over the past few decades. For respiratory conditions, targeted drug delivery directly to the site of action can achieve a high local concentration for efficacy with reduced systemic exposure and adverse effects. For systemic conditions, the unique physiology of the lung evolutionarily designed for rapid gaseous exchange presents an entry route for systemic drug delivery. Although the development of inhaled formulations has come a long way over the last few decades, many aspects of it remain to be elucidated. In particular, a reliable and well-understood method for in vitro-in vivo correlations remains to be established. With the rapid and ongoing advancement of technology, there is much potential to better utilise computational methods including different types of modelling and simulation approaches to support inhaled formulation development. This review intends to provide an introduction on some fundamental concepts in pulmonary drug delivery and inhaled formulation development followed by discussions on some challenges and opportunities in the translation of inhaled pharmaceuticals from preclinical studies to clinical development. The review concludes with some recent advancements in modelling and simulation approaches that could play an increasingly important role in modern formulation development of inhaled pharmaceuticals.

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Permeation of beta-defensin-3 encapsulated with polyethylene glycol in lung surfactant models at air-water interface

Cited by 17 publications

References 94 publications

Lipophilicity of Coarse-Grained Cholesterol Models

Lipophilicity of Coarse-Grained Cholesterol Models

Molecular Simulations of PEGylated Biomolecules, Liposomes, and Nanoparticles for Drug Delivery Applications

Contemporary Formulation Development for Inhaled Pharmaceuticals

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