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Membranes
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Dynamics of Drug Delivery to Model and Cell Membranes
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Dynamics of Drug Delivery to Model and Cell Membranes

A special issue of Membranes (ISSN 2077-0375). This special issue belongs to the section "Biological Membrane Dynamics and Computation".

Deadline for manuscript submissions: closed (15 August 2021) | Viewed by 10127

Special Issue Editor

Prof. Emiko Okamura

E-Mail Website
Guest Editor
Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 7-2-1, Kamiohno, Himeji 670-8524, Japan
Interests: in-cell NMR spectroscopy; drug delivery; real-time in-situ NMR; peptide reactions including aggregation, bond cleavage, and amino acid isomerization

Special Issue Information

Dear Colleagues

The delivery of drugs to natural cell membranes is crucial as a primary step of the biological action. The mobility of drugs and biomembrane constituents is a key to elucidating the membrane transport mechanisms in the cell. The membrane is a dynamic structure where molecules are always fluctuating under physiological conditions. The mechanism of drug delivery is related to the molecular dynamics in such a soft, fluid membrane interface. In this Special Issue, dynamical aspects of drug delivery to model and cell membranes are emphasized in order to gain insight into the molecular basis of the mechanisms toward final targets of the diagnosis and therapy of diseases.

Contributors are invited to submit papers concerning various aspects of dynamics in drug deliveries from a molecular to cellular scale. The Issue covers non-endocytic membrane transport, endocytosis, delivery via cell-penetrating peptides (CPP), and extracellular vesicles such as exosomes, and so on. Physical, chemical, and biological strategies to analyse the dynamical features of drug deliveries are also welcome.

Prof. Emiko Okamura
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Membranes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • dynamics
  • drug delivery
  • membrane transport
  • endocytosis
  • cell-penetrating peptide
  • exosome
  • analytical method

Published Papers (3 papers)

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Research

17 pages, 3268 KiB  
Article
Formulation and Bioavailability of Novel Mucoadhesive Buccal Films for Candesartan Cilexetil in Rats
by Omar Y. Mady, Mahmoud M. A. Abulmeaty, Ahmed A. Donia, Abdulaziz A. Al-Khureif, Adam A. Al-Shoubki, Manal Abudawood and Doaa A. Abdel Moety
Membranes 2021, 11(9), 659; https://doi.org/10.3390/membranes11090659 - 26 Aug 2021
Cited by 10 | Viewed by 3882
Abstract
Candesartan cilexetil (CC) is an antihypertensive drug. It has low solubility and faces hepatic first-pass metabolism after oral ingestion. We formulated bioadhesive buccal films and studied the respective drug pharmacokinetics. Different bioadhesive films were prepared (40, 80, 120, 160, 200, and 240 mg [...] Read more.
Candesartan cilexetil (CC) is an antihypertensive drug. It has low solubility and faces hepatic first-pass metabolism after oral ingestion. We formulated bioadhesive buccal films and studied the respective drug pharmacokinetics. Different bioadhesive films were prepared (40, 80, 120, 160, 200, and 240 mg CC per film) by using the solvent casting method. The drug concentrations used affect the drug entrapment mechanism, which was reflected in the film physicochemical properties like thickness, weight, drug content, bioadhesion, and drug release. Low drug concentration (F2, 40 mg per film) led to minute drug crystal dispersion while increasing the drug concentration (F7, 240 mg per film) showed drug crystal encapsulation, which affects the drug release. The drug pharmacokinetic from the prepared films was studied compared to the oral form by serial blood sampling via an inserted catheter in the carotid of rats. High-Performance Liquid Chromatography assay was used to measure the plasma concentration of CC in different forms. Compared to other films, the F2 showed the highest maximal concentration (Cmax) and the lowest elimination half-life (t1/2). Bioadhesion buccal film of CC has better bioavailability, especially at low concentrations. The ease, robustness, and ruggedness of the preparation suggests the same procedure for drugs like CC. Full article
(This article belongs to the Special Issue Dynamics of Drug Delivery to Model and Cell Membranes)
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11 pages, 2290 KiB  
Article
Synergistic Effect of Chemical Penetration Enhancers on Lidocaine Permeability Revealed by Coarse-Grained Molecular Dynamics Simulations
by Marine E. Bozdaganyan and Philipp S. Orekhov
Membranes 2021, 11(6), 410; https://doi.org/10.3390/membranes11060410 - 29 May 2021
Cited by 6 | Viewed by 3141
Abstract
The search for new formulations for transdermal drug delivery (TDD) is an important field in medicine and cosmetology. Molecules with specific physicochemical properties which can increase the permeability of active ingredients across the stratum corneum (SC) are called chemical penetration enhancers (CPEs), and [...] Read more.
The search for new formulations for transdermal drug delivery (TDD) is an important field in medicine and cosmetology. Molecules with specific physicochemical properties which can increase the permeability of active ingredients across the stratum corneum (SC) are called chemical penetration enhancers (CPEs), and it was shown that some CPEs can act synergistically. In this study, we performed coarse-grained (CG) molecular dynamics (MD) simulations of the lidocaine delivery facilitated by two CPEs—linoleic acid (LA) and ethanol—through the SC model membrane containing cholesterol, N-Stearoylsphingosine (DCPE), and behenic acid. In our simulations, we probed the effects of individual CPEs as well as their combination on various properties of the SC membrane and the lidocaine penetration across it. We demonstrated that the addition of both CPEs decreases the membrane thickness and the order parameters of the DPCE hydrocarbon chains. Moreover, LA also enhances diffusion of the SC membrane components, especially cholesterol. The estimated potential of mean force (PMF) profiles for the lidocaine translocation across SC in the presence/absence of two individual CPEs and their combination demonstrated that while ethanol lowers the free energy barrier for lidocaine to enter SC, LA decreases the depth of the free energy minima for lidocaine inside SC. These two effects supposedly result in synergistic penetration enhancement of drugs. Altogether, the present simulations provide a detailed molecular picture of CPEs’ action and their synergistic effect on the penetration of small molecular weight therapeutics that can be beneficial for the design of novel drug and cosmetics formulations. Full article
(This article belongs to the Special Issue Dynamics of Drug Delivery to Model and Cell Membranes)
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16 pages, 12788 KiB  
Article
Interactions of Linear Analogues of Battacin with Negatively Charged Lipid Membranes
by Kinga Burdach, Dagmara Tymecka, Aneta Urban, Robert Lasek, Dariusz Bartosik and Slawomir Sek
Membranes 2021, 11(3), 192; https://doi.org/10.3390/membranes11030192 - 10 Mar 2021
Cited by 5 | Viewed by 2329
Abstract
The increasing resistance of bacteria to available antibiotics has stimulated the search for new antimicrobial compounds with less specific mechanisms of action. These include the ability to disrupt the structure of the cell membrane, which in turn leads to its damage. In this [...] Read more.
The increasing resistance of bacteria to available antibiotics has stimulated the search for new antimicrobial compounds with less specific mechanisms of action. These include the ability to disrupt the structure of the cell membrane, which in turn leads to its damage. In this context, amphiphilic lipopeptides belong to the class of the compounds which may fulfill this requirement. In this paper, we describe two linear analogues of battacin with modified acyl chains to tune the balance between the hydrophilic and hydrophobic portion of lipopeptides. We demonstrate that both compounds display antimicrobial activity with the lowest values of minimum inhibitory concentrations found for Gram-positive pathogens. Therefore, their mechanism of action was evaluated on a molecular level using model lipid films mimicking the membrane of Gram-positive bacteria. The surface pressure measurements revealed that both lipopeptides show ability to bind and incorporate into the lipid monolayers, resulting in decreased ordering of lipids and membrane fluidization. Atomic force microscopy (AFM) imaging demonstrated that the exposure of the model bilayers to lipopeptides leads to a transition from the ordered gel phase to disordered liquid crystalline phase. This observation was confirmed by attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) results, which revealed that lipopeptide action causes a substantial increase in the average tilt angle of lipid acyl chains with respect to the surface normal to compensate for lipopeptide insertion into the membrane. Moreover, the peptide moieties in both molecules do not adopt any well-defined secondary structure upon binding with the lipid membrane. It was also observed that a small difference in the structure of a lipophilic chain, altering the balance between hydrophobic and hydrophilic portion of the molecules, results in different insertion depth of the active compounds. Full article
(This article belongs to the Special Issue Dynamics of Drug Delivery to Model and Cell Membranes)
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