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Pharmaceutics beyond Liposomes: Versatile Carriers and Templates from Bioceramic and Mineral Materials for Drug Delivery and Tissue Engineering

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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 (20 September 2022) | Viewed by 25976

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Special Issue Editors

Dr. Yulia I. Svenskaya

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Guest Editor

Science Medical Center, Saratov State University, Astrakhanskaya str. 83, 410012 Saratov, Russia
Interests: drug delivery; controlled release systems; theranostics; nanotechnology for biomedical applications; vaterite particles; nanocomposite structures; polyelectrolyte capsules; hair follicles; magnetic targeting; targeted delivery of photosensitizers; transdermal drug administration for the treatment of skin disorders; vitiligo treatment; antifungal therapy
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Dr. Denis V. Voronin

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Department of Physical and Colloid Chemistry, National University of Oil and Gas «Gubkin University», Leninsky Prospekt 65-1, Moscow 119991, Russia
Interests: layer-by-layer assembly; polyelectrolyte capsules; targeted delivery systems; encapsulation; magnetic nanoparticles; nanocomposite materials; hybrid materials; magnetically responsive systems; phase-change materials; thermo-regulating materials; natural mineral carriers; halloysite; vaterite; nanocellulose

Dr. Tatiana N. Borodina

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Guest Editor

Federal Scientific Research Center “Crystallography and Photonics” Russian Academy of Sciences, Leninsky Prospekt, 59, 119333 Moscow, Russia
Interests: polymer and materials chemistry; colloidal systems: preparation and properties investigation; synthesis, characterization, and applications of nanoparticles; surface chemistry; materials characterization; layer-by-layer (LbL) self-assembly of oppositely charged polyelectrolytes; fabrication of polymer capsules for the entrapment of various biomolecules and cells (proteins, cells, DNA etc.); novel drug delivery systems; polymer vehicles with controllable release/upload properties

Special Issue Information

Dear Colleagues,

In the last few decades, biomedicine was revolutionized by the emerging novel technologies for the design of materials with intended and adjustable properties at the micro- and nanoscale. The emerging drug delivery approaches offered site-specific targeting and controllable drug release with high efficiency and minimized side effects. This gave rise to the fields of nano- and personalized medicine, theranostics, and advanced tissue engineering. Currently, liposomes represent one of the most clinically established technologies applied for the encapsulation and delivery of a tremendous diversity of pharmaceuticals. However, a plenty of challenges in biomedicine push one to take a step beyond liposomal drug delivery. Naturally occurring bioceramic and mineral particles represent alternative vehicles with a high payload ability and controlled-release property, as well as promising templates for therapeutic platforms. Their original biocompatibility and diversity of sizes, shapes, and physicochemical properties open a wide avenue of advanced approaches to meet the foremost demands of modern biomedicine.

This Special Issue serves to highlight recent research exploiting the unique features of biocompatible inorganic (non-metallic) materials within the context of drug delivery and tissue regeneration. We cordially invite the submission of contributions dealing with the application of bioceramics and mineral materials as carriers for sustained drug delivery and as templates for therapeutic platforms with a broad range of biomedical applications.

Dr. Yulia I. Svenskaya
Dr. Denis V. Voronin
Dr. Tatiana N. Borodina
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

drug delivery
theranostics
tissue regeneration
tissue engineering
particulate delivery systems
controlled release
drug encapsulation
carriers
nano- and microcontainers
nature-derived materials
mineral materials
bioceramics
functional coatings
vaterite
calcium carbonate
calcium phosphate
hydroxyapatite
halloysite
cellulose nanofibers
composite polyelectrolyte capsules
gel capsules
hydrogels
hybrid scaffolds
injectable systems
local drug delivery
depot systems
systemic drug delivery

Published Papers (9 papers)

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Research

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14 pages, 4534 KiB

Open AccessArticle

Photoinduced Antibacterial Activity and Cytotoxicity of CdS Stabilized on Mesoporous Aluminosilicates and Silicates

by Anna Stavitskaya, Eliza Sitmukhanova, Adeliya Sayfutdinova, Elnara Khusnetdenova, Kristina Mazurova, Kirill Cherednichenko, Ekaterina Naumenko and Rawil Fakhrullin

Pharmaceutics 2022, 14(7), 1309; https://doi.org/10.3390/pharmaceutics14071309 - 21 Jun 2022

Cited by 5 | Viewed by 1634

Abstract

Inactivation of bacteria under the influence of visible light in presence of nanostructured materials is an alternative approach to overcome the serious problem of the growing resistance of pathogenic bacteria to antibiotics. Cadmium sulfide quantum dots are superefficient photocatalytic material suitable for visible light transformation. In this work, CdS nanoparticles with size of less than 10 nm (QDs) were synthesized on the surface of natural and synthetic mesoporous aluminosilicates and silicates (halloysite nanotubes, MCM-41, MCM-41/Halloysite, SBA-15). Materials containing 5–7 wt.% of CdS were characterized and tested as agents for photocatalytic bacteria degradation of Gram-positive S. aureus and Gram-negative E. coli with multiple antibiotic resistance. Eukaryotic cell viability tests were also conducted on the model cancer cells A 459. We found that the carrier affects prokaryotic and eukaryotic toxicity of CdS quantum dots. CdS/MCM-41/HNTs were assumed to be less toxic to eukaryotic cells and possess the most prominent photocatalytic antibacterial efficiency. Under visible light irradiation, it induced 100% bacterial growth inhibition at the concentration of 125 μg/mL and the bacteriostatic effect at the concentration of 63 μg/mL. CdS/MCM-41/HNTs showed 100% E. coli growth inhibition in the concentration of 1000 μg/mL under visible light irradiation. Full article

(This article belongs to the Special Issue Pharmaceutics beyond Liposomes: Versatile Carriers and Templates from Bioceramic and Mineral Materials for Drug Delivery and Tissue Engineering)

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15 pages, 30357 KiB

Open AccessArticle

WPI Hydrogels with a Prolonged Drug-Release Profile for Antimicrobial Therapy

by Valentina O. Plastun, Ekaterina S. Prikhozhdenko, Olga I. Gusliakova, Svetlana V. Raikova, Timothy E. L. Douglas, Olga A. Sindeeva and Oksana A. Mayorova

Pharmaceutics 2022, 14(6), 1199; https://doi.org/10.3390/pharmaceutics14061199 - 4 Jun 2022

Cited by 3 | Viewed by 2452

Abstract

Infectious sequelae caused by surgery are a significant problem in modern medicine due to their reduction of therapeutic effectiveness and the patients’ quality of life.Recently, new methods of local antimicrobial prophylaxis of postoperative sequelae have been actively developed. They allow high local concentrations of drugs to be achieved, increasing the antibiotic therapy’s effectiveness while reducing its side effects. We have developed and characterized antimicrobial hydrogels based on an inexpensive and biocompatible natural substance from the dairy industry—whey protein isolate—as matrices for drug delivery. The release of cefazolin from the pores of hydrogel structures directly depends on the amount of the loaded drug and occurs in a prolonged manner for three days. Simultaneously with the antibiotic release, hydrogel swelling and partial degradation occurs. The WPI hydrogels absorb solvent, doubling in size in three days and retaining cefazolin throughout the duration of the experiment. The antimicrobial activity of cefazolin-loaded WPI hydrogels against Staphylococcus aureus growth is prolonged in comparison to that of the free cefazolin. The overall cytotoxic effect of cefazolin-containing WPI hydrogels is lower than that of free antibiotics. Thus, our work shows that antimicrobial WPI hydrogels are suitable candidates for local antibiotic therapy of infectious surgical sequelae. Full article

(This article belongs to the Special Issue Pharmaceutics beyond Liposomes: Versatile Carriers and Templates from Bioceramic and Mineral Materials for Drug Delivery and Tissue Engineering)

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15 pages, 5780 KiB

Open AccessArticle

Development of Submicrocapsules Based on Co-Assembled Like-Charged Silica Nanoparticles and Detonation Nanodiamonds and Polyelectrolyte Layers

by Konstantin V. Palamarchuk, Tatiana N. Borodina, Anastasia V. Kostenko, Yury M. Chesnokov, Roman A. Kamyshinsky, Natalya P. Palamarchuk, Elena B. Yudina, Elena D. Nikolskaya, Nikita G. Yabbarov, Mariia R. Mollaeva and Tatiana V. Bukreeva

Pharmaceutics 2022, 14(3), 575; https://doi.org/10.3390/pharmaceutics14030575 - 5 Mar 2022

Cited by 5 | Viewed by 2029

Abstract

Capsules with shells based on nanoparticles of different nature co-assembled at the interface of liquid phases of emulsion are promising carriers of lipophilic drugs. To obtain such capsules, theoretically using the Derjaguin–Landau–Verwey–Overbeek (DLVO) theory and experimentally using dynamic light-scattering (DLS) and transmission electron microscopy (TEM) methods, the interaction of like-charged silica nanoparticles and detonation nanodiamonds in an aqueous solution was studied and their ratios selected for the formation of submicron-sized colloidosomes. The resulting colloidosomes were modified with additional layers of nanoparticles and polyelectrolytes, applying LbL technology. As a model anti-cancer drug, thymoquinone was loaded into the developed capsules, demonstrating a significant delay of the release as a result of colloidosome surface modification. Fluorescence flow cytometry and confocal laser scanning microscopy showed efficient internalization of the capsules by MCF7 cancer cells. The obtained results demonstrated a high potential for nanomedicine application in the field of the drug-delivery system development. Full article

(This article belongs to the Special Issue Pharmaceutics beyond Liposomes: Versatile Carriers and Templates from Bioceramic and Mineral Materials for Drug Delivery and Tissue Engineering)

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18 pages, 5158 KiB

Open AccessArticle

Permeability of the Composite Magnetic Microcapsules Triggered by a Non-Heating Low-Frequency Magnetic Field

by Ivan A. Burmistrov, Maxim M. Veselov, Alexander V. Mikheev, Tatiana N. Borodina, Tatiana V. Bukreeva, Michael A. Chuev, Sergey S. Starchikov, Igor S. Lyubutin, Vladimir V. Artemov, Dmitry N. Khmelenin, Natalia L. Klyachko and Daria B. Trushina

Pharmaceutics 2022, 14(1), 65; https://doi.org/10.3390/pharmaceutics14010065 - 28 Dec 2021

Cited by 8 | Viewed by 1925

Abstract

Nanosystems for targeted delivery and remote-controlled release of therapeutic agents has become a top priority in pharmaceutical science and drug development in recent decades. Application of a low frequency magnetic field (LFMF) as an external stimulus opens up opportunities to trigger release of the encapsulated bioactive substances with high locality and penetration ability without heating of biological tissue in vivo. Therefore, the development of novel microencapsulated drug formulations sensitive to LFMF is of paramount importance. Here, we report the result of LFMF-triggered release of the fluorescently labeled dextran from polyelectrolyte microcapsules modified with magnetic iron oxide nanoparticles. Polyelectrolyte microcapsules were obtained by a method of sequential deposition of oppositely charged poly(allylamine hydrochloride) (PAH) and poly(sodium 4-styrenesulfonate) (PSS) on the surface of colloidal vaterite particles. The synthesized single domain maghemite nanoparticles integrated into the polymer multilayers serve as magneto-mechanical actuators. We report the first systematic study of the effect of magnetic field with different frequencies on the permeability of the microcapsules. The in situ measurements of the optical density curves upon the 100 mT LFMF treatment were carried out for a range of frequencies from 30 to 150 Hz. Such fields do not cause any considerable heating of the magnetic nanoparticles but promote their rotating-oscillating mechanical motion that produces mechanical forces and deformations of the adjacent materials. We observed the changes in release of the encapsulated TRITC-dextran molecules from the PAH/PSS microcapsules upon application of the 50 Hz alternating magnetic field. The obtained results open new horizons for the design of polymer systems for triggered drug release without dangerous heating and overheating of tissues. Full article

(This article belongs to the Special Issue Pharmaceutics beyond Liposomes: Versatile Carriers and Templates from Bioceramic and Mineral Materials for Drug Delivery and Tissue Engineering)

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17 pages, 14560 KiB

Open AccessArticle

Effect of Size on Magnetic Polyelectrolyte Microcapsules Behavior: Biodistribution, Circulation Time, Interactions with Blood Cells and Immune System

by Roman Verkhovskii, Alexey Ermakov, Olga Sindeeva, Ekaterina Prikhozhdenko, Anastasiia Kozlova, Oleg Grishin, Mikhail Makarkin, Dmitry Gorin and Daniil Bratashov

Pharmaceutics 2021, 13(12), 2147; https://doi.org/10.3390/pharmaceutics13122147 - 14 Dec 2021

Cited by 8 | Viewed by 2466

Abstract

Drug carriers based on polyelectrolyte microcapsules remotely controlled with an external magnetic field are a promising drug delivery system. However, the influence of capsule parameters on microcapsules’ behavior in vivo is still ambiguous and requires additional study. Here, we discuss how the processes occurring in the blood flow influence the circulation time of magnetic polyelectrolyte microcapsules in mouse blood after injection into the blood circulatory system and their interaction with different blood components, such as WBCs and RBCs. The investigation of microcapsules ranging in diameter 1–5.5

μ

m allowed us to reveal the dynamics of their filtration by vital organs, cytotoxicity, and hemotoxicity, which is dependent on their size, alongside the efficiency of their interaction with the magnetic field. Our results show that small capsules have a long circulation time and do not affect blood cells. In contrast, the injection of large 5.5

μ

m microcapsules leads to fast filtration from the blood flow, induces the inhibition of macrophage cell line proliferation after 48 h, and causes an increase in hemolysis, depending on the carrier concentration. The obtained results reveal the possible directions of fine-tuning microcapsule parameters, maximizing capsule payload without the side effects for the blood flow or the blood cells. Full article

(This article belongs to the Special Issue Pharmaceutics beyond Liposomes: Versatile Carriers and Templates from Bioceramic and Mineral Materials for Drug Delivery and Tissue Engineering)

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16 pages, 29005 KiB

Open AccessArticle

Synthesis, Drug Release, and Antibacterial Properties of Novel Dendritic CHX-SrCl₂ and CHX-ZnCl₂ Particles

by Rui Sun, Jiaxin Zhang, Robert A. Whiley, Gleb B. Sukhorukov and Michael J. Cattell

Pharmaceutics 2021, 13(11), 1799; https://doi.org/10.3390/pharmaceutics13111799 - 27 Oct 2021

Cited by 3 | Viewed by 2270

Abstract

This work demonstrated for the first time the synthesis of novel chlorhexidine particles containing strontium and zinc, to provide an effective, affordable, and safe intervention in the treatment of recurrent infections found in Medicine and Dentistry. The CHX-SrCl₂ and CHX-ZnCl₂ particles were synthesized by co-precipitation of chlorhexidine diacetate (CHXD) and zinc chloride or strontium chloride, where particle size was manipulated by controlling processing time and temperature. The CHX-ZnCl₂ and CHX-SrCl₂ particles were characterized using SEM, FTIR, and XRD. UV-Vis using artificial saliva (pH 4 and pH 7) was used to measure the drug release and ICP-OES ion release. The antibacterial properties were examined against P. gingivalis, A. actinomycetemcomitans, and F. nucleatum subsp. Polymorphum, and cytotoxicity was evaluated using mouse fibroblast L929 cells. The novel particles were as safe as commercial CHXD, with antibacterial activity against a range of oral pathogens. UV-Vis results run in artificial saliva (pH 4 and pH 7) indicated a higher release rate in acidic rather than neutral conditions. The CHX-ZnCl₂ particles provided the functionality of a smart Zinc and CHX release, with respect to environmental pH, allowing responsive antibacterial applications in the field of medicine and dentistry. Full article

(This article belongs to the Special Issue Pharmaceutics beyond Liposomes: Versatile Carriers and Templates from Bioceramic and Mineral Materials for Drug Delivery and Tissue Engineering)

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Review

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43 pages, 6029 KiB

Open AccessReview

Hard, Soft, and Hard-and-Soft Drug Delivery Carriers Based on CaCO₃ and Alginate Biomaterials: Synthesis, Properties, Pharmaceutical Applications

by Yanqi Huang, Lin Cao, Bogdan V. Parakhonskiy and Andre G. Skirtach

Pharmaceutics 2022, 14(5), 909; https://doi.org/10.3390/pharmaceutics14050909 - 21 Apr 2022

Cited by 34 | Viewed by 4721

Abstract

Because free therapeutic drug molecules often have adverse effects on normal tissues, deliver scanty drug concentrations and exhibit a potentially low efficacy at pathological sites, various drug carriers have been developed for preclinical and clinical trials. Their physicochemical and toxicological properties are the subject of extensive research. Inorganic calcium carbonate particles are promising candidates as drug delivery carriers owning to their hardness, porous internal structure, high surface area, distinctive pH-sensitivity, low degradability, etc, while soft organic alginate hydrogels are also widely used because of their special advantages such as a high hydration, bio-adhesiveness, and non-antigenicity. Here, we review these two distinct substances as well as hybrid structures encompassing both types of carriers. Methods of their synthesis, fundamental properties and mechanisms of formation, and their respective applications are described. Furthermore, we summarize and compare similarities versus differences taking into account unique advantages and disadvantages of these drug delivery carriers. Moreover, rational combination of both carrier types due to their performance complementarity (yin-&yang properties: in general, yin is referred to for definiteness as hard, and yang is broadly taken as soft) is proposed to be used in the so-called hybrid carriers endowing them with even more advanced properties envisioned to be attractive for designing new drug delivery systems. Full article

(This article belongs to the Special Issue Pharmaceutics beyond Liposomes: Versatile Carriers and Templates from Bioceramic and Mineral Materials for Drug Delivery and Tissue Engineering)

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40 pages, 4988 KiB

Open AccessEditor’s ChoiceReview

Inorganic Nanoparticles in Bone Healing Applications

by Alexandra-Cristina Burdușel, Oana Gherasim, Ecaterina Andronescu, Alexandru Mihai Grumezescu and Anton Ficai

Pharmaceutics 2022, 14(4), 770; https://doi.org/10.3390/pharmaceutics14040770 - 31 Mar 2022

Cited by 26 | Viewed by 4755

Abstract

Modern biomedicine aims to develop integrated solutions that use medical, biotechnological, materials science, and engineering concepts to create functional alternatives for the specific, selective, and accurate management of medical conditions. In the particular case of tissue engineering, designing a model that simulates all tissue qualities and fulfills all tissue requirements is a continuous challenge in the field of bone regeneration. The therapeutic protocols used for bone healing applications are limited by the hierarchical nature and extensive vascularization of osseous tissue, especially in large bone lesions. In this regard, nanotechnology paves the way for a new era in bone treatment, repair and regeneration, by enabling the fabrication of complex nanostructures that are similar to those found in the natural bone and which exhibit multifunctional bioactivity. This review aims to lay out the tremendous outcomes of using inorganic nanoparticles in bone healing applications, including bone repair and regeneration, and modern therapeutic strategies for bone-related pathologies. Full article

(This article belongs to the Special Issue Pharmaceutics beyond Liposomes: Versatile Carriers and Templates from Bioceramic and Mineral Materials for Drug Delivery and Tissue Engineering)

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14 pages, 2275 KiB

Open AccessReview

Microfluidic Synthesis and Analysis of Bioinspired Structures Based on CaCO₃ for Potential Applications as Drug Delivery Carriers

by Ekaterina V. Lengert, Daria B. Trushina, Mikhail Soldatov and Alexey V. Ermakov

Pharmaceutics 2022, 14(1), 139; https://doi.org/10.3390/pharmaceutics14010139 - 7 Jan 2022

Cited by 11 | Viewed by 2566

Abstract

Naturally inspired biomaterials such as calcium carbonate, produced in biological systems under specific conditions, exhibit superior properties that are difficult to reproduce in a laboratory. The emergence of microfluidic technologies provides an effective approach for the synthesis of such materials, which increases the interest of researchers in the creation and investigation of crystallization processes. Besides accurate tuning of the synthesis parameters, microfluidic technologies also enable an analysis of the process in situ with a range of methods. Understanding the mechanisms behind the microfluidic biomineralization processes could open a venue for new strategies in the development of advanced materials. In this review, we summarize recent advances in microfluidic synthesis and analysis of CaCO₃-based bioinspired nano- and microparticles as well as core-shell structures on its basis. Particular attention is given to the application of calcium carbonate particles for drug delivery. Full article

(This article belongs to the Special Issue Pharmaceutics beyond Liposomes: Versatile Carriers and Templates from Bioceramic and Mineral Materials for Drug Delivery and Tissue Engineering)

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