Nanomedicine in Drug Delivery

A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 30707

Special Issue Editor

Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Biophysics/Nanomedicine, Medical University of Graz, Graz, Austria
Interests: nanomedicine; drug delivery; biomaterials; liposomes; lipoprotein mimetics; biophysical characterization; structural biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nanomedicine is an emerging field that fosters the development of novel concepts in drug delivery and the exploration of innovative treatment strategies to combat major diseases. Synthetically manufactured nanoparticles, biomimetic or bio-inspired nanocarriers, nanocomposites, and nanostructured materials with optimized properties are being considered as a new paradigm in the therapy of diseases. “Smart” nanocarriers are developed with high payload capacity to deliver new drugs, target specific cell types or tissues, cross physiological barriers to reach their target, improve the therapeutic window of drugs, and to reduce unwanted side effects. Nanomedicine-based treatment strategies include innovative pharmaceutical carriers for immunotherapy, gene therapy, or combination therapy with perspectives towards personalized medicine. However, to enable the translation from basic research to clinical applications and marketed nanopharmaceuticals, transdisciplinary approaches are needed.

The Special Issue aims to present novel nanomedicine-inspired delivery systems, including ligand-targeted nanoparticles for site-specific transport of pharmaceuticals, improved production and characterization techniques for pharmaceutical nanoparticles, and exploration of alternative routes of administration and delivery strategies. Topics may also include any aspects of functional nanomaterials in therapy. State-of-the-art research on promising nanomedicine-based drug delivery systems with perspectives for clinical translation are welcome.

Prof. Dr. Ruth Prassl
Guest Editor

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Keywords

  • nanoparticles, nanocomposites, nanostructured materials, and biomimetics for drug delivery
  • innovative nanoparticles for immunotherapy, gene therapy, or combination therapy
  • ligand-targeted nanocarriers
  • new nanoparticle production and characterization techniques
  • alternative administration routes and delivery strategies for nanopharmaceuticals
  • clinical translation

Published Papers (7 papers)

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Research

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21 pages, 2355 KiB  
Article
Cytokine-Mediated Inflammation in the Oral Cavity and Its Effect on Lipid Nanocarriers
by Carolin Tetyczka, Sonja Hartl, Ramona Jeitler, Markus Absenger-Novak, Claudia Meindl, Eleonore Fröhlich, Sabrina Riedl, Dagmar Zweytick and Eva Roblegg
Nanomaterials 2021, 11(5), 1330; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11051330 - 18 May 2021
Cited by 5 | Viewed by 2632
Abstract
Topical drug administration to the oral mucosa proves to be a promising treatment alternative for inflammatory diseases. However, disease-related changes in the cell barrier must be considered when developing such delivery systems. This study aimed at investigating the changes in the lining mucosa [...] Read more.
Topical drug administration to the oral mucosa proves to be a promising treatment alternative for inflammatory diseases. However, disease-related changes in the cell barrier must be considered when developing such delivery systems. This study aimed at investigating the changes in the lining mucosa caused by inflammation and evaluating the consequences on drug delivery systems such as nanostructured lipid carriers (NLC). For this, TR146 cells were treated with inflammatory cytokines and bacterial components. Cell viability and integrity, reactive oxygen species (ROS), and interleukin (IL)-8 release were used as endpoints to assess inflammation. Translocation of phosphatidylserine, cytoskeletal arrangement, opening of desmosomes, and cell proliferation were examined. Transport studies with NLC were performed considering active and passive pathways. The results showed that IL-1ß and tumor necrosis factor α induced inflammation by increasing IL-8 and ROS production (22-fold and 2-fold). Morphologically, loss of cell–cell connections and formation of stress fibers and hyperplasia were observed. The charge of the cell membrane shifted from neutral to negative, which increased the absorption of NLC due to the repulsive interactions between the hydrophobic negative particles and the cell membrane on the one hand, and interactions with lipophilic membrane proteins such as caveolin on the other. Full article
(This article belongs to the Special Issue Nanomedicine in Drug Delivery)
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16 pages, 3660 KiB  
Article
Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome
by Luis Sendra, Antonio Miguel, M. Carmen Navarro-Plaza, María José Herrero, José de la Higuera, Consuelo Cháfer-Pericás, Elena Aznar, M. Dolores Marcos, Ramón Martínez-Máñez, Luis Alfonso Rojas, Ramón Alemany and Salvador F. Aliño
Nanomaterials 2020, 10(6), 1183; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10061183 - 17 Jun 2020
Cited by 8 | Viewed by 2359
Abstract
Oncolytic adenoviruses are a therapeutic alternative to treat cancer based on their ability to replicate selectively in tumor cells. However, their use is limited mainly by the neutralizing antibody (Nab) immune response that prevents repeated dosing. An alternative to facilitate the DNA access [...] Read more.
Oncolytic adenoviruses are a therapeutic alternative to treat cancer based on their ability to replicate selectively in tumor cells. However, their use is limited mainly by the neutralizing antibody (Nab) immune response that prevents repeated dosing. An alternative to facilitate the DNA access to the tumor even in the presence of anti-viral Nabs could be gold nanoparticles able to transfer DNA molecules. However, the ability of these nanoparticles to carry large DNA molecules, such as an oncolytic adenovirus genome, has not been studied. In this work, gold nanoparticles were functionalized with different amounts of polyethylenimine to transfer in a safe and efficient manner a large oncolytic virus genome. Their transfer efficacy and final effect of the oncolytic virus in cancer cells are studied. For each synthesized nanoparticle, (a) DNA loading capacity, (b) complex size, (c) DNA protection ability, (d) transfection efficacy and (e) cytotoxic effect were studied. We observed that small gold nanoparticles (70–80 nm in diameter) protected DNA against nucleases and were able to transfect the ICOVIR-15 oncolytic virus genome encoded in pLR1 plasmid. In the present work, efficient transgene RNA expression, luciferase activity and viral cytopathic effect on cancer cells are reported. These results suggest gold nanoparticles to be an efficient and safe vector for oncolytic adenovirus genome transfer. Full article
(This article belongs to the Special Issue Nanomedicine in Drug Delivery)
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14 pages, 5698 KiB  
Article
Internalization of Metal–Organic Framework Nanoparticles in Human Vascular Cells: Implications for Cardiovascular Disease Therapy
by Dana E. Al-Ansari, Nura A. Mohamed, Isra Marei, Atef Zekri, Yu Kameno, Robert P. Davies, Paul D. Lickiss, Md Mizanur Rahman and Haissam Abou-Saleh
Nanomaterials 2020, 10(6), 1028; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10061028 - 27 May 2020
Cited by 11 | Viewed by 3139
Abstract
Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Alteration of endothelial cells and the underlying vasculature plays a central role in the pathogenesis of various CVDs. The application of nanoscale materials such as nanoparticles in biomedicine has opened new [...] Read more.
Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Alteration of endothelial cells and the underlying vasculature plays a central role in the pathogenesis of various CVDs. The application of nanoscale materials such as nanoparticles in biomedicine has opened new horizons in the treatment of CVDs. We have previously shown that the iron metal–organic framework nanoparticle, Materials Institut Lavoisier-89 (nanoMIL-89) represents a viable vehicle for future drug delivery of pulmonary arterial hypertension. In this study, we have assessed the cellular uptake of nanoMIL-89 in pulmonary artery endothelial and smooth muscle cells using microscopy imaging techniques. We also tested the cellular responses to nanoMIL-89 using molecular and cellular assays. Microscopic images showed cellular internalization of nanoMIL-89, packaging into endocytic vesicles, and passing to daughter cells during mitosis. Moreover, nanoMIL-89 showed anti-inflammatory activity without any significant cytotoxicity. Our results indicate that nanoMIL-89 formulation may offer promising therapeutic opportunities and set forth a new prototype for drug delivery not only in CVDs, but also for other diseases yet incurable, such as diabetes and cancer. Full article
(This article belongs to the Special Issue Nanomedicine in Drug Delivery)
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16 pages, 2836 KiB  
Article
Enhancing the Cellular Uptake and Antibacterial Activity of Rifampicin through Encapsulation in Mesoporous Silica Nanoparticles
by Paul Joyce, Hanna Ulmefors, Sajedeh Maghrebi, Santhni Subramaniam, Anthony Wignall, Silver Jõemetsa, Fredrik Höök and Clive A. Prestidge
Nanomaterials 2020, 10(4), 815; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10040815 - 24 Apr 2020
Cited by 23 | Viewed by 4441
Abstract
An urgent demand exists for the development of novel delivery systems that efficiently transport antibacterial agents across cellular membranes for the eradication of intracellular pathogens. In this study, the clinically relevant poorly water-soluble antibiotic, rifampicin, was confined within mesoporous silica nanoparticles (MSN) to [...] Read more.
An urgent demand exists for the development of novel delivery systems that efficiently transport antibacterial agents across cellular membranes for the eradication of intracellular pathogens. In this study, the clinically relevant poorly water-soluble antibiotic, rifampicin, was confined within mesoporous silica nanoparticles (MSN) to investigate their ability to serve as an efficacious nanocarrier system against small colony variants of Staphylococcus aureus (SCV S. aureus) hosted within Caco-2 cells. The surface chemistry and particle size of MSN were varied through modifications during synthesis, where 40 nm particles with high silanol group densities promoted enhanced cellular uptake. Extensive biophysical analysis was performed, using quartz crystal microbalance with dissipation (QCM-D) and total internal reflection fluorescence (TIRF) microscopy, to elucidate the mechanism of MSN adsorption onto semi-native supported lipid bilayers (snSLB) and, thus, uncover potential cellular uptake mechanisms of MSN into Caco-2 cells. Such studies revealed that MSN with reduced silanol group densities were prone to greater particle aggregation on snSLB, which was expected to restrict endocytosis. MSN adsorption and uptake into Caco-2 cells correlated well with antibacterial efficacy against SCV S. aureus, with 40 nm hydrophilic particles triggering a ~2.5-log greater reduction in colony forming units, compared to the pure rifampicin. Thus, this study provides evidence for the potential to design silica nanocarrier systems with controlled surface chemistries that can be used to re-sensitise intracellular bacteria to antibiotics by delivering them to the site of infection. Full article
(This article belongs to the Special Issue Nanomedicine in Drug Delivery)
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Review

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42 pages, 3253 KiB  
Review
Use of Protamine in Nanopharmaceuticals—A Review
by Ivana Ruseska, Katja Fresacher, Christina Petschacher and Andreas Zimmer
Nanomaterials 2021, 11(6), 1508; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11061508 - 07 Jun 2021
Cited by 37 | Viewed by 9391
Abstract
Macromolecular biomolecules are currently dethroning classical small molecule therapeutics because of their improved targeting and delivery properties. Protamine-a small polycationic peptide-represents a promising candidate. In nature, it binds and protects DNA against degradation during spermatogenesis due to electrostatic interactions between the negatively charged [...] Read more.
Macromolecular biomolecules are currently dethroning classical small molecule therapeutics because of their improved targeting and delivery properties. Protamine-a small polycationic peptide-represents a promising candidate. In nature, it binds and protects DNA against degradation during spermatogenesis due to electrostatic interactions between the negatively charged DNA-phosphate backbone and the positively charged protamine. Researchers are mimicking this technique to develop innovative nanopharmaceutical drug delivery systems, incorporating protamine as a carrier for biologically active components such as DNA or RNA. The first part of this review highlights ongoing investigations in the field of protamine-associated nanotechnology, discussing the self-assembling manufacturing process and nanoparticle engineering. Immune-modulating properties of protamine are those that lead to the second key part, which is protamine in novel vaccine technologies. Protamine-based RNA delivery systems in vaccines (some belong to the new class of mRNA-vaccines) against infectious disease and their use in cancer treatment are reviewed, and we provide an update on the current state of latest developments with protamine as pharmaceutical excipient for vaccines. Full article
(This article belongs to the Special Issue Nanomedicine in Drug Delivery)
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12 pages, 1384 KiB  
Review
Recent Advances in Lipid-Based Nanosystems for Gemcitabine and Gemcitabine–Combination Therapy
by Saffiya Habib and Moganavelli Singh
Nanomaterials 2021, 11(3), 597; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11030597 - 27 Feb 2021
Cited by 17 | Viewed by 3088
Abstract
The anti-metabolite drug gemcitabine is widely used for the treatment of a variety of cancers. At present, gemcitabine is administered as a hydrochloride salt that is delivered by slow intravenous injection in cycles of three or four weeks. Although regarded as a ‘front-line’ [...] Read more.
The anti-metabolite drug gemcitabine is widely used for the treatment of a variety of cancers. At present, gemcitabine is administered as a hydrochloride salt that is delivered by slow intravenous injection in cycles of three or four weeks. Although regarded as a ‘front-line’ chemotherapeutic agent, its efficacy is hampered by poor target cell specificity, sub-optimal cellular uptake, rapid clearance from circulation, the development of chemoresistance, and undesirable side-effects. The use of organic, inorganic, and metal-based nanoparticles as delivery agents presents an opportunity to overcome these limitations and safely harness optimal drug efficacy and enhance their therapeutic indices. Among the many and varied nano delivery agents explored, the greatest body of knowledge has been generated in the field of lipid-mediated delivery. We review here the liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, exosomes, lipid-polymer hybrids, and other novel lipid-based agents that have been developed within the past six years for the delivery of gemcitabine and its co-drugs. Full article
(This article belongs to the Special Issue Nanomedicine in Drug Delivery)
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31 pages, 4205 KiB  
Review
Black Phosphorus as Multifaceted Advanced Material Nanoplatforms for Potential Biomedical Applications
by Abhijeet Pandey, Ajinkya N. Nikam, Gasper Fernandes, Sanjay Kulkarni, Bharath Singh Padya, Ruth Prassl, Subham Das, Alex Joseph, Prashant K. Deshmukh, Pravin O. Patil and Srinivas Mutalik
Nanomaterials 2021, 11(1), 13; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11010013 - 23 Dec 2020
Cited by 31 | Viewed by 4551
Abstract
Black phosphorus is one of the emerging members of two-dimensional (2D) materials which has recently entered the biomedical field. Its anisotropic properties and infrared bandgap have enabled researchers to discover its applicability in several fields including optoelectronics, 3D printing, bioimaging, and others. Characterization [...] Read more.
Black phosphorus is one of the emerging members of two-dimensional (2D) materials which has recently entered the biomedical field. Its anisotropic properties and infrared bandgap have enabled researchers to discover its applicability in several fields including optoelectronics, 3D printing, bioimaging, and others. Characterization techniques such as Raman spectroscopy have revealed the structural information of Black phosphorus (BP) along with its fundamental properties, such as the behavior of its photons and electrons. The present review provides an overview of synthetic approaches and properties of BP, in addition to a detailed discussion about various types of surface modifications available for overcoming the stability-related drawbacks and for imparting targeting ability to synthesized nanoplatforms. The review further gives an overview of multiple characterization techniques such as spectroscopic, thermal, optical, and electron microscopic techniques for providing an insight into its fundamental properties. These characterization techniques are not only important for the analysis of the synthesized BP but also play a vital role in assessing the doping as well as the structural integrity of BP-based nanocomposites. The potential role of BP and BP-based nanocomposites for biomedical applications specifically, in the fields of drug delivery, 3D printing, and wound dressing, have been discussed in detail to provide an insight into the multifunctional role of BP-based nanoplatforms for the management of various diseases, including cancer therapy. The review further sheds light on the role of BP-based 2D platforms such as BP nanosheets along with BP-based 0D platforms—i.e., BP quantum dots in the field of therapy and bioimaging of cancer using techniques such as photoacoustic imaging and fluorescence imaging. Although the review inculcates the multimodal therapeutic as well as imaging role of BP, there is still research going on in this field which will help in the development of BP-based theranostic platforms not only for cancer therapy, but various other diseases. Full article
(This article belongs to the Special Issue Nanomedicine in Drug Delivery)
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