Membranes

Editorial

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3 pages, 196 KiB

Open AccessEditorial

Special Issue on Drug–Membrane Interactions

by Marina Pinheiro

Membranes 2021, 11(10), 764; https://doi.org/10.3390/membranes11100764 - 01 Oct 2021

Cited by 2 | Viewed by 1503

Abstract

Drug–membrane interactions immediately occur when drugs are administered, independently of the route of administration or the target location (i [...] Full article

(This article belongs to the Special Issue Study on Drug-Membrane Interactions)

Research

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19 pages, 4390 KiB

Open AccessArticle

How Insertion of a Single Tryptophan in the N-Terminus of a Cecropin A-Melittin Hybrid Peptide Changes Its Antimicrobial and Biophysical Profile

by Ana Rita Ferreira, Cátia Teixeira, Carla F. Sousa, Lucinda J. Bessa, Paula Gomes and Paula Gameiro

Membranes 2021, 11(1), 48; https://doi.org/10.3390/membranes11010048 - 12 Jan 2021

Cited by 11 | Viewed by 2803

Abstract

In the era of antibiotic resistance, there is an urgent need for efficient antibiotic therapies to fight bacterial infections. Cationic antimicrobial peptides (CAMP) are promising lead compounds given their membrane-targeted mechanism of action, and high affinity towards the anionic composition of bacterial membranes. [...] Read more.

In the era of antibiotic resistance, there is an urgent need for efficient antibiotic therapies to fight bacterial infections. Cationic antimicrobial peptides (CAMP) are promising lead compounds given their membrane-targeted mechanism of action, and high affinity towards the anionic composition of bacterial membranes. We present a new CAMP, W-BP100, derived from the highly active BP100, holding an additional tryptophan at the N-terminus. W-BP100 showed a broader antibacterial activity, demonstrating a potent activity against Gram-positive strains. Revealing a high partition constant towards anionic over zwitterionic large unilamellar vesicles and inducing membrane saturation at a high peptide/lipid ratio, W-BP100 has a preferential location for hydrophobic environments. Contrary to BP100, almost no aggregation of anionic vesicles is observed around saturation conditions and at higher concentrations no aggregation is observed. With these results, it is possible to state that with the incorporation of a single tryptophan to the N-terminus, a highly active peptide was obtained due to the π–electron system of tryptophan, resulting in negatively charged clouds, that participate in cation–π interactions with lysine residues. Furthermore, we propose that W-BP100 action can be achieved by electrostatic interactions followed by peptide translocation. Full article

(This article belongs to the Special Issue Study on Drug-Membrane Interactions)

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12 pages, 1907 KiB

Open AccessArticle

Unraveling the Role of Drug-Lipid Interactions in NSAIDs-Induced Cardiotoxicity

by Catarina Pereira-Leite, Marina Figueiredo, Kinga Burdach, Cláudia Nunes and Salette Reis

Membranes 2021, 11(1), 24; https://doi.org/10.3390/membranes11010024 - 29 Dec 2020

Cited by 16 | Viewed by 2437

Abstract

Cardiovascular (CV) toxicity is nowadays recognized as a class effect of non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs). However, their mechanisms of cardiotoxicity are not yet well understood, since different compounds with similar action mechanisms exhibit distinct cardiotoxicity. For instance, diclofenac (DIC) is among the [...] Read more.

Cardiovascular (CV) toxicity is nowadays recognized as a class effect of non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs). However, their mechanisms of cardiotoxicity are not yet well understood, since different compounds with similar action mechanisms exhibit distinct cardiotoxicity. For instance, diclofenac (DIC) is among the most cardiotoxic compounds, while naproxen (NAP) is associated with low CV risk. In this sense, this study aimed to unravel the role of drug-lipid interactions in NSAIDs-induced cardiotoxicity. For that, DIC and NAP interactions with lipid bilayers as model systems of cell and mitochondrial membranes were characterized by derivative spectrophotometry, fluorometric leakage assays, and synchrotron X-ray scattering. Both DIC and NAP were found to have the ability to permeabilize the membrane models, as well as to alter the bilayers’ structure. The NSAIDs-induced modifications were dependent on the lipid composition of the membrane model, the three-dimensional structure of the drug, as well as the drug:lipid molar ratio tested. Altogether, this work supports the hypothesis that NSAIDs-lipid interactions, in particular at the mitochondrial level, may be another key step among the mechanisms underlying NSAIDs-induced cardiotoxicity. Full article

(This article belongs to the Special Issue Study on Drug-Membrane Interactions)

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12 pages, 2907 KiB

Open AccessArticle

Insights into the Membranolytic Activity of Antimalarial Drug-Cell Penetrating Peptide Conjugates

by Luísa Aguiar, Marina Pinheiro, Ana Rute Neves, Nuno Vale, Sira Defaus, David Andreu, Salette Reis and Paula Gomes

Membranes 2021, 11(1), 4; https://doi.org/10.3390/membranes11010004 - 22 Dec 2020

Cited by 3 | Viewed by 2055

Abstract

Conjugation of TP10, a cell-penetrating peptide with intrinsic antimalarial activity, to the well-known antimalarial drugs chloroquine and primaquine has been previously shown to enhance the peptide’s action against, respectively, blood- and liver-stage malaria parasites. Yet, this was achieved at the cost of a [...] Read more.

Conjugation of TP10, a cell-penetrating peptide with intrinsic antimalarial activity, to the well-known antimalarial drugs chloroquine and primaquine has been previously shown to enhance the peptide’s action against, respectively, blood- and liver-stage malaria parasites. Yet, this was achieved at the cost of a significant increase in haemolytic activity, as fluorescence microscopy and flow cytometry studies showed the conjugates to be more haemolytic for non-infected than for Plasmodium-infected red blood cells. To gain further insight into how these conjugates distinctively bind, and likely disrupt, membranes of both Plasmodium-infected and non-infected erythrocytes, we used dynamic light scattering and surface plasmon resonance to study the interactions of two representative conjugates and their parent compounds with lipid model membranes. Results obtained are herein reported and confirm that a strong membrane-disruptive character underlies the haemolytic properties of these conjugates, thus hampering their ability to exert selective antimalarial action. Full article

(This article belongs to the Special Issue Study on Drug-Membrane Interactions)

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18 pages, 1192 KiB

Open AccessArticle

Fluoroquinolone Metalloantibiotics to Bypass Antimicrobial Resistance Mechanisms: Decreased Permeation through Porins

by Mariana Ferreira, Carla F. Sousa and Paula Gameiro

Membranes 2021, 11(1), 3; https://doi.org/10.3390/membranes11010003 - 22 Dec 2020

Cited by 6 | Viewed by 2029

Abstract

Fluoroquinolones (FQs) are broad-spectrum antibiotics largely used in the clinical practice against Gram-negative and some Gram-positive bacteria. Nevertheless, bacteria have developed several antimicrobial resistance mechanisms against such class of antibiotics. Ternary complexes of FQs, copper(II) and phenanthroline, known as metalloantibiotics, arise in an [...] Read more.

Fluoroquinolones (FQs) are broad-spectrum antibiotics largely used in the clinical practice against Gram-negative and some Gram-positive bacteria. Nevertheless, bacteria have developed several antimicrobial resistance mechanisms against such class of antibiotics. Ternary complexes of FQs, copper(II) and phenanthroline, known as metalloantibiotics, arise in an attempt to counteract an antibiotic resistance mechanism related to low membrane permeability. These metalloantibiotics seem to use an alternative influx route, independent of porins. The translocation pathways of five FQs and its metalloantibiotics were studied through biophysical experiments, allowing us to infer about the role of OmpF porin in the influx. The FQ-OmpF interaction was assessed in mimetic membrane systems differing on the lipidic composition, disclosing no interference of the lipidic composition. The drug-porin interaction revealed similar values for the association constants of FQs and metalloantibiotics with native OmpF. Therefore, OmpF mutants and specific quenchers were used to study the location-association relationship, comparing a free FQ and its metalloantibiotic. The free FQ revealed a specific association, with preference for residues on the centre of OmpF, while the metalloantibiotic showed a random interaction. Thereby, metalloantibiotics may be an alternative to pure FQs, being able to overcome some antimicrobial resistance mechanism of Gram-negative bacteria related to decreased membrane permeability. Full article

(This article belongs to the Special Issue Study on Drug-Membrane Interactions)

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16 pages, 6615 KiB

Open AccessArticle

Analysis of Dynamics Targeting CNT-Based Drug Delivery through Lung Cancer Cells: Design, Simulation, and Computational Approach

by Nafiseh Sohrabi, Afshar Alihosseini, Vahid Pirouzfar and Maysam Zamani Pedram

Membranes 2020, 10(10), 283; https://doi.org/10.3390/membranes10100283 - 14 Oct 2020

Cited by 15 | Viewed by 2688

Abstract

Nowadays, carbon nano (CN) structures and specifically carbon nanotubes (CNTs), because of the nanotube’s nanoscale shape, are widely used in carrier and separation applications. The conjugation of CNTs with polysaccharide, proteins, drugs, and magnetic nanoparticles provides a chance for smart targeting and trajectory [...] Read more.

Nowadays, carbon nano (CN) structures and specifically carbon nanotubes (CNTs), because of the nanotube’s nanoscale shape, are widely used in carrier and separation applications. The conjugation of CNTs with polysaccharide, proteins, drugs, and magnetic nanoparticles provides a chance for smart targeting and trajectory manipulation, which are used in the crucial field of life science applications, including for cancer disease diagnostics and treatments. Providing an optimal procedure for delivering a drug to a specific area based on mathematical criteria is key in systemic delivery design. Trajectory guidance and applied force control are the main parameters affected by systemic delivery. Moreover, a better understanding of the tissue parameters and cell membrane molecular behaviour are other factors that can be indirectly affected by the targeted delivery. Both sides are an essential part of successful targeting. The lung is one of the challenging organs for drug delivery inside the human body. It has a large surface area with a thin epithelium layer. A few severe diseases directly involve human lung cells, and optimal and successful drug delivery to the lung for the treatment procedure is vital. In this paper, we studied functionalized CNTs’ targeted delivery via crossing through the lung cell membrane. Molecular dynamics (MD) software simulated all the interaction forces. Mathematical modelling of the cell membrane and proposed delivery system based on the relation of velocity and force has been considered. Dynamics equations for CNTs were defined in the time and frequency domain using control theory methods. The proposed delivery system consists of two main parts: crossing through the cell membrane and targeting inside the cell. For both steps, a mathematical model and a proper magnetic field profile have been proposed. The designed system provides criteria for crossing through the cell membrane within 30 s to 5 min and a translocation profile of 1 to 100 Å. Full article

(This article belongs to the Special Issue Study on Drug-Membrane Interactions)

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Review

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22 pages, 4759 KiB

Open AccessReview

Current Status of Amino Acid-Based Permeation Enhancers in Transdermal Drug Delivery

by Rui Pereira, Sandra G. Silva, Marina Pinheiro, Salette Reis and M. Luísa do Vale

Membranes 2021, 11(5), 343; https://doi.org/10.3390/membranes11050343 - 07 May 2021

Cited by 25 | Viewed by 5556

Abstract

Transdermal drug delivery (TDD) presents many advantages compared to other conventional routes of drug administration, yet its full potential has not been achieved. The administration of drugs through the skin is hampered by the natural barrier properties of the skin, which results in [...] Read more.

Transdermal drug delivery (TDD) presents many advantages compared to other conventional routes of drug administration, yet its full potential has not been achieved. The administration of drugs through the skin is hampered by the natural barrier properties of the skin, which results in poor permeation of most drugs. Several methods have been developed to overcome this limitation. One of the approaches to increase drug permeation and thus to enable TDD for a wider range of drugs consists in the use of chemical permeation enhancers (CPEs), compounds that interact with skin to ultimately increase drug flux. Amino acid derivatives show great potential as permeation enhancers, as they exhibit high biodegradability and low toxicity. Here we present an overview of amino acid derivatives investigated so far as CPEs for the delivery of hydrophilic and lipophilic drugs across the skin, focusing on the structural features which promote their enhancement capacity. Full article

(This article belongs to the Special Issue Study on Drug-Membrane Interactions)

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21 pages, 1440 KiB

Open AccessEditor’s ChoiceReview

A Reevaluation of Chitosan-Decorated Nanoparticles to Cross the Blood-Brain Barrier

by Hernán Cortés, Sergio Alcalá-Alcalá, Isaac H. Caballero-Florán, Sergio A. Bernal-Chávez, Arturo Ávalos-Fuentes, Maykel González-Torres, Manuel González-Del Carmen, Gabriela Figueroa-González, Octavio D. Reyes-Hernández, Benjamín Floran, María L. Del Prado-Audelo and Gerardo Leyva-Gómez

Membranes 2020, 10(9), 212; https://doi.org/10.3390/membranes10090212 - 30 Aug 2020

Cited by 53 | Viewed by 5349

Abstract

The blood-brain barrier (BBB) is a sophisticated and very selective dynamic interface composed of endothelial cells expressing enzymes, transport systems, and receptors that regulate the passage of nutrients, ions, oxygen, and other essential molecules to the brain, regulating its homeostasis. Moreover, the BBB [...] Read more.

The blood-brain barrier (BBB) is a sophisticated and very selective dynamic interface composed of endothelial cells expressing enzymes, transport systems, and receptors that regulate the passage of nutrients, ions, oxygen, and other essential molecules to the brain, regulating its homeostasis. Moreover, the BBB performs a vital function in protecting the brain from pathogens and other dangerous agents in the blood circulation. Despite its crucial role, this barrier represents a difficult obstacle for the treatment of brain diseases because many therapeutic agents cannot cross it. Thus, different strategies based on nanoparticles have been explored in recent years. Concerning this, chitosan-decorated nanoparticles have demonstrated enormous potential for drug delivery across the BBB and treatment of Alzheimer’s disease, Parkinson’s disease, gliomas, cerebral ischemia, and schizophrenia. Our main objective was to highlight the high potential of chitosan adsorption to improve the penetrability through the BBB of nanoformulations for diseases of CNS. Therefore, we describe the BBB structure and function, as well as the routes of chitosan for crossing it. Moreover, we define the methods of decoration of nanoparticles with chitosan and provide numerous examples of their potential utilization in a variety of brain diseases. Lastly, we discuss future directions, mentioning the need for extensive characterization of proposed nanoformulations and clinical trials for evaluation of their efficacy. Full article

(This article belongs to the Special Issue Study on Drug-Membrane Interactions)

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