State-of-the-Art Nanomaterials and Nanotechnology in Drug Delivery and Release

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

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 73960

Special Issue Editors

Department of Mechanical and Aerospace Engineering, Politecnico di Torino, 10129 Torino, Italy
Interests: cancer nanomedicine; polyurethanes; drug delivery
Special Issues, Collections and Topics in MDPI journals
Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy
Interests: polymeric biomaterials; tissue engineering; drug delivery; vectors for nanomedicine; tissue and organ models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the past decade, nanotechnology-based drug delivery systems have gained increasing interest because of their ability to overcome the well-known drawbacks of systemic drug administration, such as poor patient compliance, and severe side effects in non-target tissues and organs.

Nanosystems in the form of nanoparticles, nanocomposites, nanogels, inclusion complexes, and stimuli-responsive nanohydrogels offer multiple advantages, such as localized drug delivery, target-specificity, and extended and triggered drug release, thereby improving efficacy, stability, and tolerability of active agents.

To facilitate the translation of nanosystems to clinical practice, a better understanding of their interactions with the biological milieu at different levels (e.g., cells, tissues), their bio-distribution, and their fate is of paramount importance. For instance, bioengineered three-dimensional organ or tissue models have been introduced as screening tools for nanosystems, being more cost-effective and of reduced ethical impact than animal tests.

This Special Issue aims to provide readers with a snapshot of the new design strategies for smart and targeted drug delivery nanosystems, as well as of the advanced testing tools based on bio-engineered tissue and organ mimics.

We welcome the submission of original research articles and short communications, as well as reviews, mini-reviews, and systematic review articles that cover, but are not limited to, the following topics:

  1. Nanosystem design and characterization.
  2. Surface or bulk functionalized nanosystems for active targeting.
  3. Stimuli-responsive nanosystems for triggered drug delivery.
  4. Safety, stability, biodistribution, tolerability, and fate of nanosystems.
  5. Bioengineered three-dimensional models for nanosystem testing.
  6. Regulatory aspects of nanosystem introduction into clinical practice.

Dr. Monica Boffito
Dr. Clara Mattu
Prof. Dr. Gianluca Ciardelli
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. Nanomaterials is an international peer-reviewed open access semimonthly 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

  • nanotechnology
  • nanosystems
  • nanoparticles
  • nanocomposites
  • nanohydrogels
  • drug delivery
  • drug release
  • active targeting
  • stimuli-responsiveness
  • regenerative pharmacology
  • bioengineered 3D in vitro models
  • inclusion complexes
  • nanosystem fate/biodistribution/safety/stability/tolerability

Published Papers (6 papers)

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Research

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16 pages, 3820 KiB  
Article
Magneto-Mechanically Triggered Thick Films for Drug Delivery Micropumps
by Georgiana Dolete, Cristina Chircov, Ludmila Motelica, Denisa Ficai, Ovidiu-Cristian Oprea, Marin Gheorghe, Anton Ficai and Ecaterina Andronescu
Nanomaterials 2022, 12(20), 3598; https://0-doi-org.brum.beds.ac.uk/10.3390/nano12203598 - 13 Oct 2022
Cited by 6 | Viewed by 1464
Abstract
Given the demanding use of controlled drug delivery systems, our attention was focused on developing a magnetic film that can be triggered in the presence of a magnetic field for both drug delivery and the actuating mechanism in micropump biomedical microelectromechanical systems (BioMEMS). [...] Read more.
Given the demanding use of controlled drug delivery systems, our attention was focused on developing a magnetic film that can be triggered in the presence of a magnetic field for both drug delivery and the actuating mechanism in micropump biomedical microelectromechanical systems (BioMEMS). Magnetic alginate films were fabricated in three steps: the co-precipitation of iron salts in an alkaline environment to obtain magnetite nanoparticles (Fe3O4), the mixing of the obtained nanoparticles with a sodium alginate solution containing glycerol as a plasticizer and folic acid as an active substance, and finally the casting of the final solution in a Petri dish followed by cross-linking with calcium chloride solution. Magnetite nanoparticles were incorporated in the alginate matrix because of the well-established biocompatibility of both materials, a property that would make the film convenient for implantable BioMEMS devices. The obtained film was analyzed in terms of its magnetic, structural, and morphological properties. To demonstrate the hypothesis that the magnetic field can be used to trigger drug release from the films, we studied the release profile in an aqueous medium (pH = 8) using a NdFeB magnet as a triggering factor. Full article
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31 pages, 5928 KiB  
Article
Anti-EGFR Targeted Multifunctional I-131 Radio-Nanotherapeutic for Treating Osteosarcoma: In Vitro 3D Tumor Spheroid Model
by Suphalak Khamruang Marshall, Boonyisa Saelim, Maneerat Taweesap, Verachai Pachana, Yada Panrak, Naritsara Makchuchit and Passara Jaroenpakdee
Nanomaterials 2022, 12(19), 3517; https://0-doi-org.brum.beds.ac.uk/10.3390/nano12193517 - 08 Oct 2022
Cited by 7 | Viewed by 60745
Abstract
The systemic delivery of doxorubicin (DOX) to treat osteosarcoma requires an adequate drug concentration to be effective, but in doing so, it raises the risk of increasing organ off-target toxicity and developing drug resistance. Herein, this study reveals a multiple therapeutic nanocarrier delivery [...] Read more.
The systemic delivery of doxorubicin (DOX) to treat osteosarcoma requires an adequate drug concentration to be effective, but in doing so, it raises the risk of increasing organ off-target toxicity and developing drug resistance. Herein, this study reveals a multiple therapeutic nanocarrier delivery platform that overcomes off-target toxicity by providing good specificity and imparting enhanced tumor penetration in a three-dimensional (3D) human MG-63 spheroid model. By synthesizing PEG-PLGA nanoparticles by the double emulsion method, encapsulating DOX and Na131I in the inner core, and conjugating with an epidermal growth factor receptor (EGFR) antibody, it is intended to specifically target human MG-63 cells. The nanocarrier is biocompatible with blood and has good stability characteristics. Na131I encapsulation efficiency was >96%, and radiochemical purity was >96% over 96 h. A DOX encapsulation efficacy of ~80% was achieved, with a drug loading efficiency of ~3%, and a sustained DOX release over 5 days. The nanocarrier EGFR antibody achieved a ~80-fold greater targeting efficacy to MG-63 cells (EGFR+) than fibroblast cells (EGFR−). The targeted multiple therapeutic DIE-NPs have a higher penetration and uptake of Na131I to the 3D model and a ~3-fold higher cytotoxicity than the DOX monotherapy (D-NPs). The co-administration of DOX and Na131I (DIE-NPs) disrupts DNA repair and generates free radicals resulting in DNA damage, triggering the activation of apoptosis pathways. This leads to inhibition of MG-63 cell proliferation and promotes cell cycle arrest in the G0/G1 phase. Furthermore, the PEGylated anti-EGFR functionalized DIE-NPs were found to be biocompatible with red blood cells and to have no adverse effects. This anti-EGFR targeted multifunctional I-131 radio-nanotherapeutic signifies a customizable specific targeted treatment for osteosarcoma. Full article
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20 pages, 2579 KiB  
Article
Tween® Preserves Enzyme Activity and Stability in PLGA Nanoparticles
by Jason Thomas Duskey, Ilaria Ottonelli, Arianna Rinaldi, Irene Parmeggiani, Barbara Zambelli, Leon Z. Wang, Robert K. Prud’homme, Maria Angela Vandelli, Giovanni Tosi and Barbara Ruozi
Nanomaterials 2021, 11(11), 2946; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11112946 - 03 Nov 2021
Cited by 11 | Viewed by 2404
Abstract
Enzymes, as natural and potentially long-term treatment options, have become one of the most sought-after pharmaceutical molecules to be delivered with nanoparticles (NPs); however, their instability during formulation often leads to underwhelming results. Various molecules, including the Tween® polysorbate series, have demonstrated [...] Read more.
Enzymes, as natural and potentially long-term treatment options, have become one of the most sought-after pharmaceutical molecules to be delivered with nanoparticles (NPs); however, their instability during formulation often leads to underwhelming results. Various molecules, including the Tween® polysorbate series, have demonstrated enzyme activity protection but are often used uncontrolled without optimization. Here, poly(lactic-co-glycolic) acid (PLGA) NPs loaded with β-glucosidase (β-Glu) solutions containing Tween® 20, 60, or 80 were compared. Mixing the enzyme with Tween® pre-formulation had no effect on particle size or physical characteristics, but increased the amount of enzyme loaded. More importantly, NPs made with Tween® 20:enzyme solutions maintained significantly higher enzyme activity. Therefore, Tween® 20:enzyme solutions ranging from 60:1 to 2419:1 mol:mol were further analyzed. Isothermal titration calorimetry analysis demonstrated low affinity and unquantifiable binding between Tween® 20 and β-Glu. Incorporating these solutions in NPs showed no effect on size, zeta potential, or morphology. The amount of enzyme and Tween® 20 in the NPs was constant for all samples, but a trend towards higher activity with higher molar rapports of Tween® 20:β-Glu was observed. Finally, a burst release from NPs in the first hour with Tween®:β-Glu solutions was the same as free enzyme, but the enzyme remained active longer in solution. These results highlight the importance of stabilizers during NP formulation and how optimizing their use to stabilize an enzyme can help researchers design more efficient and effective enzyme loaded NPs. Full article
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23 pages, 4060 KiB  
Article
Iron-Doped ZnO Nanoparticles as Multifunctional Nanoplatforms for Theranostics
by Marco Carofiglio, Marco Laurenti, Veronica Vighetto, Luisa Racca, Sugata Barui, Nadia Garino, Roberto Gerbaldo, Francesco Laviano and Valentina Cauda
Nanomaterials 2021, 11(10), 2628; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11102628 - 06 Oct 2021
Cited by 25 | Viewed by 2962
Abstract
Zinc oxide nanoparticles (ZnO NPs) are currently among the most promising nanomaterials for theranostics. However, they suffer from some drawbacks that could prevent their application in nanomedicine as theranostic agents. The doping of ZnO NPs can be effectively exploited to enhance the already-existing [...] Read more.
Zinc oxide nanoparticles (ZnO NPs) are currently among the most promising nanomaterials for theranostics. However, they suffer from some drawbacks that could prevent their application in nanomedicine as theranostic agents. The doping of ZnO NPs can be effectively exploited to enhance the already-existing ZnO properties and introduce completely new functionalities in the doped material. Herein, we propose a novel synthetic approach for iron-doped ZnO (Fe:ZnO) NPs as a multifunctional theranostic nanoplatform aimed at cancer cell treatment. Pure ZnO and Fe:ZnO NPs, with two different levels of iron doping, were synthesized by a rapid wet-chemical method and analyzed in terms of morphology, crystal structure and chemical composition. Interestingly, Fe:ZnO NPs featured bioimaging potentialities thanks to superior optical properties and novel magnetic responsiveness. Moreover, iron doping provides a way to enhance the electromechanical behavior of the NPs, which are then expected to show enhanced therapeutic functionalities. Finally, the intrinsic therapeutic potentialities of the NPs were tested in terms of cytotoxicity and cellular uptake with both healthy B lymphocytes and cancerous Burkitt’s lymphoma cells. Furthermore, their biocompatibility was tested with a pancreatic ductal adenocarcinoma cell line (BxPC-3), where the novel properties of the proposed iron-doped ZnO NPs can be potentially exploited for theranostics. Full article
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14 pages, 13786 KiB  
Article
Data-Driven Modeling of the Cellular Pharmacokinetics of Degradable Chitosan-Based Nanoparticles
by Huw D. Summers, Carla P. Gomes, Aida Varela-Moreira, Ana P. Spencer, Maria Gomez-Lazaro, Ana P. Pêgo and Paul Rees
Nanomaterials 2021, 11(10), 2606; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11102606 - 03 Oct 2021
Cited by 2 | Viewed by 1986
Abstract
Nanoparticle drug delivery vehicles introduce multiple pharmacokinetic processes, with the delivery, accumulation, and stability of the therapeutic molecule influenced by nanoscale processes. Therefore, considering the complexity of the multiple interactions, the use of data-driven models has critical importance in understanding the interplay between [...] Read more.
Nanoparticle drug delivery vehicles introduce multiple pharmacokinetic processes, with the delivery, accumulation, and stability of the therapeutic molecule influenced by nanoscale processes. Therefore, considering the complexity of the multiple interactions, the use of data-driven models has critical importance in understanding the interplay between controlling processes. We demonstrate data simulation techniques to reproduce the time-dependent dose of trimethyl chitosan nanoparticles in an ND7/23 neuronal cell line, used as an in vitro model of native peripheral sensory neurons. Derived analytical expressions of the mean dose per cell accurately capture the pharmacokinetics by including a declining delivery rate and an intracellular particle degradation process. Comparison with experiment indicates a supply time constant, τ = 2 h. and a degradation rate constant, b = 0.71 h−1. Modeling the dose heterogeneity uses simulated data distributions, with time dependence incorporated by transforming data-bin values. The simulations mimic the dynamic nature of cell-to-cell dose variation and explain the observed trend of increasing numbers of high-dose cells at early time points, followed by a shift in distribution peak to lower dose between 4 to 8 h and a static dose profile beyond 8 h. Full article
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Review

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21 pages, 1596 KiB  
Review
In Vitro Models of Bacterial Biofilms: Innovative Tools to Improve Understanding and Treatment of Infections
by G. Crivello, L. Fracchia, G. Ciardelli, M. Boffito and C. Mattu
Nanomaterials 2023, 13(5), 904; https://0-doi-org.brum.beds.ac.uk/10.3390/nano13050904 - 27 Feb 2023
Cited by 5 | Viewed by 2504
Abstract
Bacterial infections are a growing concern to the health care systems. Bacteria in the human body are often found embedded in a dense 3D structure, the biofilm, which makes their eradication even more challenging. Indeed, bacteria in biofilm are protected from external hazards [...] Read more.
Bacterial infections are a growing concern to the health care systems. Bacteria in the human body are often found embedded in a dense 3D structure, the biofilm, which makes their eradication even more challenging. Indeed, bacteria in biofilm are protected from external hazards and are more prone to develop antibiotic resistance. Moreover, biofilms are highly heterogeneous, with properties dependent on the bacteria species, the anatomic localization, and the nutrient/flow conditions. Therefore, antibiotic screening and testing would strongly benefit from reliable in vitro models of bacterial biofilms. This review article summarizes the main features of biofilms, with particular focus on parameters affecting biofilm composition and mechanical properties. Moreover, a thorough overview of the in vitro biofilm models recently developed is presented, focusing on both traditional and advanced approaches. Static, dynamic, and microcosm models are described, and their main features, advantages, and disadvantages are compared and discussed. Full article
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