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Application of Layer-by-Layer Self-Assembled Nanocoating for Drug Delivery

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 23252

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Special Issue Editors

Prof. Dr. Melgardt de Villiers

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Guest Editor

School of Pharmacy, University of Wisconsin Madison, Madison, WI 53706, USA
Interests: nanotechnology; dendrimers; compounding; amorphous; nanocoating

Dr. Daniel P. Otto

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Guest Editor

Laboratory for Analytical Services, Research Focus Area for Chemical Resource Beneficiation, North-West University, Potchefstroom, South Africa
Interests: drug delivery; LbL nanocoating; surfactants; colloids; NMR
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Special Issue Information

Dear Colleagues,

This Special Issue will focus on the application of nanoshells based on layer-by-layer adsorption of oppositely charged macromolecules onto a substrate and their application in drug delivery and targeting. This technique was introduced in the early 1990s and has been used to form nanoshells around drug and protein cores. The basis of the method involves resaturation of polyion adsorption, resulting in reversal of the terminal surface charge of the film after deposition of each layer. This method provides the possibility of designing ultrathin multilayer films with a precision better than one nanometer in defined molecular composition. By manipulating both the ratio of wall to core and the wall composition, the shells can be precisely tuned, for example, to control the release of macromolecule drugs. No covalent binding is involved in shell formation, which allows the drug or macromolecules to remain intact. Empty nanocapsules can also be prepared after thin-film coatings are formed on colloidal cores that can be dissolved. These empty capsules can be loaded with a drug via diffusion. Controlled release of the capsule interior may be achieved with pH or temperature change, or through external physical influences such as IR laser impulses or alternate magnetic fields. Different templates such as organic and inorganic colloid particles, protein aggregates, and drug nanocrystals, with sizes ranging from a few nanometers to tens of microns, can be coated with these nanoorganized multilayer films. Various materials, e.g., synthetic polyelectrolytes, chitosan and its derivatives, proteins, DNA, lipids, multivalent dyes, and magnetic nanoparticles, can be used to fabricate the designed nanoshell to adjust the required stability, biocompatibility, and affinity properties of the coatings.

For this Special Issue, we seek both reviews and research articles covering the general topics represented by following keywords.

Prof. Dr. Melgardt de Villiers
Dr. Daniel P. Otto
Guest Editors

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. Pharmaceutics 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 2900 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

layer-by-layer
nanocoating
drug delivery
self-assembly
polyelectrolyte/dendrimer

Published Papers (7 papers)

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Research

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19 pages, 2954 KiB

Open AccessArticle

In Vitro Skin Delivery of Griseofulvin by Layer-by-Layer Nanocoated Emulsions Stabilized by Whey Protein and Polysaccharides

by Daniel P. Otto, Anja Otto and Melgardt M. de Villiers

Pharmaceutics 2022, 14(3), 554; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14030554 - 02 Mar 2022

Cited by 6 | Viewed by 1925

Abstract

Griseofulvin is a poorly water-soluble drug administered orally to treat topical fungal infections of the skin and hair. However, oral administration leads to poor and unpredictable drug pharmacokinetics. Additionally, griseofulvin is unstable in the presence of light. A layer-by-layer (LbL) nanocoating approach was employed to curb these shortcomings by stabilizing emulsions, lyophilized emulsions, and reconstituted emulsions with a layer each of whey protein, and either hyaluronic acid, amylopectin, or alginic acid, which captured the drug. The coating materials are biological, environmentally benign, and plentiful. Photostability studies indicated that the LbL particles afforded 6 h of protection of the topical application. In vitro absorption studies showed that griseofulvin concentrated preferentially in the stratum corneum, with virtually no transdermal delivery. Therefore, LbL-nanocoated emulsions, lyophilized particles, and reconstituted lyophilized emulsions can produce a viable topical delivery system to treat superficial fungal infections. Full article

(This article belongs to the Special Issue Application of Layer-by-Layer Self-Assembled Nanocoating for Drug Delivery)

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26 pages, 6420 KiB

Open AccessArticle

Modified Desolvation Method Enables Simple One-Step Synthesis of Gelatin Nanoparticles from Different Gelatin Types with Any Bloom Values

by Pavel Khramtsov, Oksana Burdina, Sergey Lazarev, Anastasia Novokshonova, Maria Bochkova, Valeria Timganova, Dmitriy Kiselkov, Artem Minin, Svetlana Zamorina and Mikhail Rayev

Pharmaceutics 2021, 13(10), 1537; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101537 - 22 Sep 2021

Cited by 16 | Viewed by 3793

Abstract

Gelatin nanoparticles found numerous applications in drug delivery, bioimaging, immunotherapy, and vaccine development as well as in biotechnology and food science. Synthesis of gelatin nanoparticles is usually made by a two-step desolvation method, which, despite providing stable and homogeneous nanoparticles, has many limitations, namely complex procedure, low yields, and poor reproducibility of the first desolvation step. Herein, we present a modified one-step desolvation method, which enables the quick, simple, and reproducible synthesis of gelatin nanoparticles. Using the proposed method one can prepare gelatin nanoparticles from any type of gelatin with any bloom number, even with the lowest ones, which remains unattainable for the traditional two-step technique. The method relies on quick one-time addition of poor solvent (preferably isopropyl alcohol) to gelatin solution in the absence of stirring. We applied the modified desolvation method to synthesize nanoparticles from porcine, bovine, and fish gelatin with bloom values from 62 to 225 on the hundreds-of-milligram scale. Synthesized nanoparticles had average diameters between 130 and 190 nm and narrow size distribution. Yields of synthesis were 62–82% and can be further increased. Gelatin nanoparticles have good colloidal stability and withstand autoclaving. Moreover, they were non-toxic to human immune cells. Full article

(This article belongs to the Special Issue Application of Layer-by-Layer Self-Assembled Nanocoating for Drug Delivery)

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18 pages, 5574 KiB

Open AccessArticle

The Metabolic Response of Various Cell Lines to Microtubule-Driven Uptake of Lipid- and Polymer-Coated Layer-by-Layer Microcarriers

by Claudia Claus, Robert Fritz, Erik Schilling and Uta Reibetanz

Pharmaceutics 2021, 13(9), 1441; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091441 - 10 Sep 2021

Cited by 1 | Viewed by 1805

Abstract

Lipid structures, such as liposomes or micelles, are of high interest as an approach to support the transport and delivery of active agents as a drug delivery system. However, there are many open questions regarding their uptake and impact on cellular metabolism. In this study, lipid structures were assembled as a supported lipid bilayer on top of biopolymer-coated microcarriers based on the Layer-by-Layer assembly strategy. The functionalized microcarriers were then applied to various human and animal cell lines in addition to primary human macrophages (MΦ). Here, their influence on cellular metabolism and their intracellular localization were detected by extracellular flux analysis and immunofluorescence analysis, respectively. The impact of microcarriers on metabolic parameters was in most cell types rather low. However, lipid bilayer-supported microcarriers induced a decrease in oxygen consumption rate (OCR, indicative for mitochondrial respiration) and extracellular acidification rate (ECAR, indicative for glycolysis) in Vero cells. Additionally, in Vero cells lipid bilayer microcarriers showed a more pronounced association with microtubule filaments than polymer-coated microcarrier. Furthermore, they localized to a perinuclear region and induced nuclei with some deformations at a higher rate than unfunctionalized carriers. This association was reduced through the application of the microtubule polymerization inhibitor nocodazole. Thus, the effect of respective lipid structures as a drug delivery system on cells has to be considered in the context of the respective target cell, but in general can be regarded as rather low. Full article

(This article belongs to the Special Issue Application of Layer-by-Layer Self-Assembled Nanocoating for Drug Delivery)

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Graphical abstract

18 pages, 7788 KiB

Open AccessArticle

Revisiting the Cytotoxicity of Cationic Polyelectrolytes as a Principal Component in Layer-by-Layer Assembly Fabrication

by Ekaterina Naumenko, Farida Akhatova, Elvira Rozhina and Rawil Fakhrullin

Pharmaceutics 2021, 13(8), 1230; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081230 - 09 Aug 2021

Cited by 10 | Viewed by 2656

Abstract

Polycations are an essential part of layer-by-layer (LbL)-assembled drug delivery systems, especially for gene delivery. In addition, they are used for other related applications, such as cell surface engineering. As a result, an assessment of the cytotoxicity of polycations and elucidation of the mechanisms of polycation toxicity is of paramount importance. In this study, we examined in detail the effects of a variety of water-soluble, positively charged synthetic polyelectrolytes on in vitro cytotoxicity, cell and nucleus morphology, and monolayer expansion changes. We have ranked the most popular cationic polyelectrolytes from the safest to the most toxic in relation to cell cultures. 3D cellular cluster formation was disturbed by addition of polyelectrolytes in most cases in a dose-dependent manner. Atomic force microscopy allowed us to visualize in detail the structures of the polyelectrolyte–DNA complexes formed due to electrostatic interactions. Our results indicate a relationship between the structure of the polyelectrolytes and their toxicity, which is necessary for optimization of drug and gene delivery systems. Full article

(This article belongs to the Special Issue Application of Layer-by-Layer Self-Assembled Nanocoating for Drug Delivery)

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26 pages, 14563 KiB

Open AccessArticle

Layer-by-Layer Nanoparticles of Tamoxifen and Resveratrol for Dual Drug Delivery System and Potential Triple-Negative Breast Cancer Treatment

by Ali A. Al-jubori, Ghassan M. Sulaiman, Amer T. Tawfeeq, Hamdoon A. Mohammed, Riaz A. Khan and Salman A. A. Mohammed

Pharmaceutics 2021, 13(7), 1098; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13071098 - 20 Jul 2021

Cited by 42 | Viewed by 4660

Abstract

Nanoparticle development demonstrates use in various physicochemical, biological, and functional properties for biomedical applications, including anti-cancer applications. In the current study, a cancer therapeutic conjugate was produced consisting of tamoxifen (TAM) and resveratrol (RES) by layer-by-layer (LbL) nanoparticles based on lipid-based drug delivery systems and liquid crystalline nanoparticles (LCNPs) coated with multiple layers of positively charged chitosan and negatively charged hyaluronic acid for the evaluation of biocompatibility and therapeutic properties against cancer cells. Multiple techniques characterized the synthesis of TAM/RES–LbL-LCNPs, such as Fourier-transform infrared spectroscopy (FTIR), X-ray crystallography (XRD), Zeta potential analysis, particle size analysis, Field Emission Scanning Electron Microscope (FESEM), and Transmission electron microscopy (TEM). The in vitro cytotoxic effects of TAM/RES–LbL-LCNPs were investigated against human breast cancer cell line, Michigan Cancer Foundation-7 (MCF-7), and human triple-negative breast cancer cell line, Centre Antoine Lacassagne-51 (CAL-51), using various parameters. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay confirmed that the treatment of cells with TAM/RES–LbL-LCNPs caused a reduction in cell proliferation, and no such inhibition was observed with human normal liver cell line: American Type Culture Collection Cell Line-48 (WRL-68 [ATCC CL-48]). Fluorescent microscopy examined the ability of Fluorescein isothiocyanate (FITC) to bind to TAM/RES–LbL-LCNPs along with their cellular uptake. Apoptosis determination was performed using hematoxylin–eosin and acridine orange–propidium iodide double staining. The expression of P53 and caspase-8 was analyzed by flow cytometry analysis. An in vivo study determined the toxicity of TAM/RES–LbL-LCNPs in mice and assessed the functional marker changes in the liver and kidneys. No significant statistical differences were found for the tested indicators. TAM/RES–LbL-LCNP treatment showed no apparent damages or histopathological abnormalities in the heart, lung, liver, spleen, and kidney histological images. The current findings observed for the first time propose that TAM/RES–LbL-LCNPs provide a new and safer method to use phytochemicals in combinatorial therapy and provide a novel treatment approach against breast cancers. Full article

(This article belongs to the Special Issue Application of Layer-by-Layer Self-Assembled Nanocoating for Drug Delivery)

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Review

Jump to: Research

27 pages, 4012 KiB

Open AccessReview

Layer-by-Layer Cell Encapsulation for Drug Delivery: The History, Technique Basis, and Applications

by Wenyan Li, Xuejiao Lei, Hua Feng, Bingyun Li, Jiming Kong and Malcolm Xing

Pharmaceutics 2022, 14(2), 297; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14020297 - 27 Jan 2022

Cited by 20 | Viewed by 4249

Abstract

The encapsulation of cells with various polyelectrolytes through layer-by-layer (LbL) has become a popular strategy in cellular function engineering. The technique sprang up in 1990s and obtained tremendous advances in multi-functionalized encapsulation of cells in recent years. This review comprehensively summarized the basis and applications in drug delivery by means of LbL cell encapsulation. To begin with, the concept and brief history of LbL and LbL cell encapsulation were introduced. Next, diverse types of materials, including naturally extracted and chemically synthesized, were exhibited, followed by a complicated basis of LbL assembly, such as interactions within multilayers, charge distribution, and films morphology. Furthermore, the review focused on the protective effects against adverse factors, and bioactive payloads incorporation could be realized via LbL cell encapsulation. Additionally, the payload delivery from cell encapsulation system could be adjusted by environment, redox, biological processes, and functional linkers to release payloads in controlled manners. In short, drug delivery via LbL cell encapsulation, which takes advantage of both cell grafts and drug activities, will be of great importance in basic research of cell science and biotherapy for various diseases. Full article

(This article belongs to the Special Issue Application of Layer-by-Layer Self-Assembled Nanocoating for Drug Delivery)

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22 pages, 3595 KiB

Open AccessReview

Polyelectrolyte Encapsulation and Confinement within Protein Cage-Inspired Nanocompartments

by Qing Liu, Ahmed Shaukat, Daniella Kyllönen and Mauri A. Kostiainen

Pharmaceutics 2021, 13(10), 1551; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101551 - 24 Sep 2021

Cited by 5 | Viewed by 3007

Abstract

Protein cages are nanocompartments with a well-defined structure and monodisperse size. They are composed of several individual subunits and can be categorized as viral and non-viral protein cages. Native viral cages often exhibit a cationic interior, which binds the anionic nucleic acid genome through electrostatic interactions leading to efficient encapsulation. Non-viral cages can carry various cargo, ranging from small molecules to inorganic nanoparticles. Both cage types can be functionalized at targeted locations through genetic engineering or chemical modification to entrap materials through interactions that are inaccessible to wild-type cages. Moreover, the limited number of constitutional subunits ease the modification efforts, because a single modification on the subunit can lead to multiple functional sites on the cage surface. Increasing efforts have also been dedicated to the assembly of protein cage-mimicking structures or templated protein coatings. This review focuses on native and modified protein cages that have been used to encapsulate and package polyelectrolyte cargos and on the electrostatic interactions that are the driving force for the assembly of such structures. Selective encapsulation can protect the payload from the surroundings, shield the potential toxicity or even enhance the intended performance of the payload, which is appealing in drug or gene delivery and imaging. Full article

(This article belongs to the Special Issue Application of Layer-by-Layer Self-Assembled Nanocoating for Drug Delivery)

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