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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Nanomedicine and Nanobiology".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 36442

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Dr. Elisabete M. S. Castanheira

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Physics Centre of Minho and Porto Universities (CF-UM-UP), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Interests: drug delivery systems; magnetic and plasmonic nanoparticles; (magneto)liposomes; bionanomaterials; combined cancer therapy
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Dr. Sérgio R. S. Veloso

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Physics Centre of Minho and Porto Universities (CF-UM-UP), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Interests: drug delivery systems; biomaterials; nanomaterials; colloids and interfaces; nanomedicine; nanosystems for theranostics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the last several decades, nanomedicine has provided various high-performance tools to overcome biomedical challenges that have resulted in numerous patents. Particularly, drug delivery systems enabled the surpassing of drug stability and solubility limits, improved the routes for drug administration, reduced the dose-associated toxicity, and enhanced the target specificity by exploring both active and passive delivery strategies.

The combination of different nanomaterials has opened paths for the development of smart multifunctional drug delivery systems, for example, the synergistic use of both therapeutic and diagnostic agents (i.e., theranostic agents) in a single drug carrier. These advancements have enabled the spatial and temporal manipulation of drug delivery systems and thus on-demand drug release upon an external stimulus. This control over drug release remains a major challenge, moving towards multimodal and multifunctional strategies as a means to optimize efficiency and efficacy.

This Special Issue aims to attract the academic and scientific communities within this biomedical field to contribute their developments in drug delivery systems based on nanomaterials. Original research articles and reviews are welcome, including those providing a fundamental understanding of the principles, fabrication, and application of traditional or innovative systems that demonstrate an advantage over current clinical formulations. The systems can include (but are not limited to) biomaterials, carbonaceous materials, as well as magnetic and/or plasmonic materials

Dr. Elisabete M. S. Castanheira
Dr. Sérgio R. S. Veloso
Guest Editors

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Keywords

drug delivery systems
on-demand delivery
target therapy
theranostic
nanomedicine
nanoparticles
nanomaterials
biomaterials
multifunctional materials

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Advances in Nanomaterials for Drug Delivery 2.0 in Biomedicines (5 articles)

Published Papers (12 papers)

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Editorial

Jump to: Research, Review

3 pages, 199 KiB

Open AccessEditorial

Advances in Nanomaterials for Drug Delivery

by Sérgio R. S. Veloso and Elisabete M. S. Castanheira

Biomedicines 2023, 11(2), 399; https://doi.org/10.3390/biomedicines11020399 - 29 Jan 2023

Viewed by 1375

Abstract

In recent years, nanomedicine has provided several high-performance tools for overcoming biomedical challenges, resulting in numerous patents [...] Full article

(This article belongs to the Special Issue Advances in Nanomaterials for Drug Delivery)

Research

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16 pages, 2025 KiB

Open AccessArticle

Curcumin Hybrid Lipid Polymeric Nanoparticles: Antioxidant Activity, Immune Cellular Response, and Cytotoxicity Evaluation

by María Isabel Quirós-Fallas, Krissia Wilhelm-Romero, Silvia Quesada-Mora, Gabriela Azofeifa-Cordero, Luis Felipe Vargas-Huertas, Diego Alvarado-Corella, Juan José Mora-Román, José Roberto Vega-Baudrit, Mirtha Navarro-Hoyos and Andrea Mariela Araya-Sibaja

Biomedicines 2022, 10(10), 2431; https://doi.org/10.3390/biomedicines10102431 - 29 Sep 2022

Cited by 6 | Viewed by 2170

Abstract

Poor solubility and short biological half-life present a challenge that needs to be overcome in order to improve the recognized bioactivities of curcumin (CUR), the main phenolic compounds derived from the roots of Curcuma longa. However, drug delivery systems have proven to be an excellent strategy to improve and obtain greater bioavailability. Our previous studies on curcuminoid hybrid nanoparticles have shown promising results by significantly increasing the solubility of desmethoxycurcumin (DMC) and bisdemethoxycurcumin (BDM). In this contribution, we performed a detailed characterization of a CUR as well as in vitro and in vivo studies. The developed method produced CUR loaded nanoparticles with an average size of 49.46 ± 0.80. Moreover, the FT-IR analysis confirmed the encapsulation, and TEM images showed their spherical shape. The NP achieved an encapsulation efficiency greater than 99%. Further, the release studies found that the NPs obtained a significantly higher release than the pure compounds in water. In vivo delayed-type hypersensitivity (DTH) studies showed promising results by enhancing the immune activity response of CUR in NP compared to bulk CUR. Furthermore, we report a significant increase in antioxidant activity for CUR-NP in aqueous solution compared to free CUR. Finally, an important in vitro cytotoxic effect on gastric AGS and colon SW620 adenocarcinoma cell lines was found for CUR-NP while empty carrier nanoparticles are observed to exhibit low cytotoxicity, indicating the potential of these CUR-PLU NPs for further studies to assess their phytotherapeutic applications. Full article

(This article belongs to the Special Issue Advances in Nanomaterials for Drug Delivery)

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15 pages, 20262 KiB

Open AccessArticle

Molecularly Imprinted Nanoparticles towards MMP9 for Controlling Cardiac ECM after Myocardial Infarction: A Predictive Experimental-Computational Chemistry Investigation

by Anthea Villano, Giovanni Barcaro, Susanna Monti, Niccoletta Barbani, Antonio Rizzo, Daniela Rossin, Raffaella Rastaldo, Claudia Giachino and Caterina Cristallini

Biomedicines 2022, 10(9), 2070; https://doi.org/10.3390/biomedicines10092070 - 24 Aug 2022

Cited by 7 | Viewed by 2193

Abstract

The recent advances in nanotechnology are revolutionizing preventive and therapeutic approaches to treating cardiovascular diseases. Controlling the extracellular matrix metalloproteinase (MMP) activation and expression in the failing human left ventricular myocardium represents a significant therapeutic target for heart disease. In this study, we used molecularly imprinting polymers (MIPs) to restore the correct balance between MMPs and their tissue inhibitors (TIMPs), and explored the potential of this technique exhaustively through chemical synthesis, physicochemical and biological characterizations, and computational chemistry methods. By molecular dynamics simulations based on classical force fields, we simulated the early stages of the imprinting process in solution disclosing the pivotal interaction established between the monomers and the MMP9 protein template. The average interaction energies of methacrylic acid (MAA) and poly (ethylene glycol) ethyl ether methacrylate (PEG) units were in the ranges 17–22 and 30–37 kcal/mol, respectively. At low coverage, the PEG monomers seemed firmly anchored to the protein surface and were not displaced by water, while only about 20% of MAA was replaced by water. The synthesis of MIPs was successfully with a monomer conversion higher than 99% and the production of spherical particles with average diameter of 344 ± 33 nm. HPLC analysis showed a specific recognition factor of MMP9 on MIPs of about 1.3. FT-IR Chemical Imaging confirmed the mechanisms necessary to generate a “selective memory” of the MIPs towards the enzyme. HPLC results indicated that the rebound amount of both TIMP1 and MMP2 to MIPs is lower than that of the template, showing a selectivity factor of 2.1 and 2.3, respectively. Preliminary tests on the effect of MIPs on H9C2 cells revealed that this treatment has no cytotoxic effects. Full article

(This article belongs to the Special Issue Advances in Nanomaterials for Drug Delivery)

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24 pages, 5995 KiB

Open AccessArticle

Therapeutic Potential of Quercetin Loaded Nanoparticles: Novel Insights in Alleviating Colitis in an Experimental DSS Induced Colitis Model

by Safaa I. Khater, Marwa M. Lotfy, Maher N. Alandiyjany, Leena S. Alqahtani, Asmaa W. Zaglool, Fayez Althobaiti, Tamer Ahmed Ismail, Mohamed Mohamed Soliman, Saydat Saad and Doaa Ibrahim

Biomedicines 2022, 10(7), 1654; https://doi.org/10.3390/biomedicines10071654 - 9 Jul 2022

Cited by 24 | Viewed by 3585

Abstract

Oxidative stress is considered the main etiologic factor involved in inflammatory bowel disease (IBD). Integration of nanocarriers for natural therapeutic agents with antioxidant and anti-inflammatory potential is a novel promising candidate for curing IBD. Herein, the colonic antioxidant and anti-inflammatory effects of different concentrations of quercetin nanoparticles (QT-NPs) were evaluated using a dextran sulfate sodium (DSS)-induced colitis model. Following colitis induction, the efficacy and mechanistic actions of QT-NPs were evaluated by assessing lesion severity, molecular aids controlling oxidative stress and inflammatory response, and histopathological and immunohistochemistry examination of colonic tissues. Administration of QT-NPs, especially at higher concentrations, significantly reduced the disease activity index and values of fecal calprotectin marker compared to the colitic group. Colonic oxidant/antioxidant status (ROS, H₂O₂, MDA, SOD, CAT, GPX and TAC) was restored after treatment with higher concentrations of QT-NPs. Moreover, QT-NPs at levels of 20 mg/kg and, to a lesser extent, 15 mg/kg reduced Nrf2 and HO-1 gene expression, which was in line with decreasing the expression of iNOS and COX2 in colonic tissues. Higher concentrations of QT-NPs greatly downregulated pro-inflammatory cytokines; upregulated genes encoding occludin, MUC-2 and JAM; and restored the healthy architectures of colonic tissues. Taken together, these data suggest that QT-NPs could be a promising alternative to current IBD treatments. Full article

(This article belongs to the Special Issue Advances in Nanomaterials for Drug Delivery)

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15 pages, 1963 KiB

Open AccessArticle

Enhanced Antibacterial Activity of a Cationic Macromolecule by Its Complexation with a Weakly Active Pyrazole Derivative

by Anna Maria Schito, Debora Caviglia, Chiara Brullo, Alessia Zorzoli, Danilo Marimpietri and Silvana Alfei

Biomedicines 2022, 10(7), 1607; https://doi.org/10.3390/biomedicines10071607 - 6 Jul 2022

Cited by 4 | Viewed by 1609

Abstract

Molecules containing the pyrazole nucleus are widely reported as promising candidates to develop new antimicrobial compounds against multidrug-resistant (MDR) bacteria, where available antibiotics may fail. Recently, aiming at improving the too-high minimum inhibitory concentrations (MICs) of a pyrazole hydrochloride salt (CB1H), CB1H-loaded nanoparticles (CB1H-P7 NPs) were developed using a potent cationic bactericidal macromolecule (P7) as polymer matrix. Here, CB1H-P7 NPs have been successfully tested on several clinical isolates of Gram-positive and Gram-negative species, including relevant MDR strains. CB1H-P7 NPs displayed very low MICs (0.6–4.8 µM), often two-fold lower than those of P7, on 34 out of 36 isolates tested. Upon complexation, the antibacterial effects of pristine CB1H were improved by 2–16.4-fold, and, unexpectedly, also the already potent antibacterial effects of P7 were 2–8 times improved against most of bacteria tested when complexed with CB1H. Time-killing experiments performed on selected species established that CB1H-P7 NPs were bactericidal against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Selectivity indices values up to 2.4, determined by cytotoxicity experiments on human keratinocytes, suggested that CB1H-P7 NPs could be promising for counteracting serious infections sustained by most of the isolates tested in this study. Full article

(This article belongs to the Special Issue Advances in Nanomaterials for Drug Delivery)

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16 pages, 2320 KiB

Open AccessArticle

The Peptide/Antibody-Based Surface Decoration of Calcium Phosphate Nanoparticles Carrying siRNA Influences the p65 NF-κB Protein Expression in Inflamed Cells In Vitro

by Elena K. Müller, Nataniel Białas, Matthias Epple and Ingrid Hilger

Biomedicines 2022, 10(7), 1571; https://doi.org/10.3390/biomedicines10071571 - 1 Jul 2022

Cited by 2 | Viewed by 1845

Abstract

Earlier studies with nanoparticles carrying siRNA were restricted to investigating the inhibition of target-specific protein expression, while almost ignoring effects related to the nanoparticle composition. Here, we demonstrate how the design and surface decoration of nanoparticles impact the p65 nuclear factor-kappa B (NF-κB) protein expression in inflamed leucocytes and endothelial cells in vitro. We prepared silica-coated calcium phosphate nanoparticles carrying encapsulated siRNA against p65 NF-κB and surface-decorated with peptides or antibodies. We show that RGD-decorated nanoparticles are efficient in down-regulating p65 NF-κB protein expression in endothelial cells as a result of an enhanced specific cellular binding and subsequent uptake of nanoparticles. In contrast, nanoparticles decorated with IgG (whether specific or not for CD69) are efficient in down-regulating p65 NF-κB protein expression in T-cells, but not in B-cells. Thus, an optimized nanoparticle decoration with xenogenic IgG may stimulate a specific cellular uptake. In summary, the composition of siRNA-loaded calcium phosphate nanoparticles can either weaken or stimulate p65 NF-κB protein expression in targeted inflamed leucocytes and endothelial cells. In general, unveiling such interactions may be very useful for the future design of anti-p65 siRNA-based nanomedicines for treatment of inflammation-associated diseases. Full article

(This article belongs to the Special Issue Advances in Nanomaterials for Drug Delivery)

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19 pages, 3347 KiB

Open AccessArticle

Solid Magnetoliposomes as Multi-Stimuli-Responsive Systems for Controlled Release of Doxorubicin: Assessment of Lipid Formulations

by Beatriz D. Cardoso, Vanessa F. Cardoso, Senetxu Lanceros-Méndez and Elisabete M. S. Castanheira

Biomedicines 2022, 10(5), 1207; https://doi.org/10.3390/biomedicines10051207 - 23 May 2022

Cited by 8 | Viewed by 3053

Abstract

Stimuli-responsive liposomes are a class of nanocarriers whose drug release occurs, preferentially, when exposed to a specific biological environment, to an external stimulus, or both. This work is focused on the design of solid magnetoliposomes (SMLs) as lipid-based nanosystems aiming to obtain multi-stimuli-responsive vesicles for doxorubicin (DOX) controlled release in pathological areas under the action of thermal, magnetic, and pH stimuli. The effect of lipid combinations on structural, colloidal stability, and thermodynamic parameters were evaluated. The results confirmed the reproducibility for SMLs synthesis based on nine lipid formulations (combining DPPC, DSPC, CHEMS, DOPE and/or DSPE-PEG), with structural and colloidal properties suitable for biological applications. A loss of stability and thermosensitivity was observed for formulations containing dioleoylphosphatidylethanolamine (DOPE) lipid. SMLs PEGylation is an essential step to enhance both their long-term storage stability and stealth properties. DOX encapsulation (encapsulation efficiency ranging between 87% and 96%) in the bilayers lowered its pK_a, which favors the displacement of DOX from the acyl chains to the surface when changing from alkaline to acidic pH. The release profiles demonstrated a preferential release at acidic pH, more pronounced under mimetic mild-hyperthermia conditions (42 °C). Release kinetics varied with the lipid formulation, generally demonstrating hyperthermia temperatures and acidic pH as determining factors in DOX release; PEGylation was shown to act as a diffusion barrier on the SMLs surface. The integrated assessment and characterization of SMLs allows tuning lipid formulations that best respond to the needs for specific controlled release profiles of stimuli-responsive nanosystems as a multi-functional approach to cancer targeting and therapy. Full article

(This article belongs to the Special Issue Advances in Nanomaterials for Drug Delivery)

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17 pages, 1969 KiB

Open AccessArticle

Ammonium Glycyrrhizinate and Bergamot Essential Oil Co-Loaded Ultradeformable Nanocarriers: An Effective Natural Nanomedicine for In Vivo Anti-Inflammatory Topical Therapies

by Maria Chiara Cristiano, Nicola d’Avanzo, Antonia Mancuso, Martine Tarsitano, Antonella Barone, Daniele Torella, Donatella Paolino and Massimo Fresta

Biomedicines 2022, 10(5), 1039; https://doi.org/10.3390/biomedicines10051039 - 30 Apr 2022

Cited by 15 | Viewed by 2606

Abstract

Bergamot essential oil (BEO) and Ammonium glycyrrhizinate (AG), naturally derived compounds, have remarkable anti-inflammatory properties, thus making them suitable candidates for the treatment of skin disorders. Despite this, their inadequate physicochemical properties strongly compromise their topical application. Ultradeformable nanocarriers containing both BEO and AG were used to allow their passage through the skin, thus maximizing their therapeutic activity. Physicochemical characterization studies were performed using Zetasizer Nano ZS and Turbiscan Lab^®. The dialysis method was used to investigate the release profile of the active compounds. In vivo studies were performed on human healthy volunteers through the X-Rite spectrophotometer. The nanosystems showed suitable features for topical cutaneous administration in terms of mean size, surface charge, size distribution, and long-term stability/storability. The co-delivery of BEO and AG in the deformable systems improved both the release profile kinetic of ammonium glycyrrhizinate and deformability properties of the resulting nanosystems. The topical cutaneous administration on human volunteers confirmed the efficacy of the nanosystems. In detail, BEO and AG-co-loaded ultradeformable vesicles showed a superior activity compared to that recorded from the ones containing AG as a single agent. These results are promising and strongly encourage a potential topical application of AG/BEO co-loaded nanocarriers for anti-inflammatory therapies. Full article

(This article belongs to the Special Issue Advances in Nanomaterials for Drug Delivery)

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21 pages, 20663 KiB

Open AccessArticle

Pyrazole-Based Water-Soluble Dendrimer Nanoparticles as a Potential New Agent against Staphylococci

by Silvana Alfei, Chiara Brullo, Debora Caviglia, Gabriella Piatti, Alessia Zorzoli, Danilo Marimpietri, Guendalina Zuccari and Anna Maria Schito

Biomedicines 2022, 10(1), 17; https://doi.org/10.3390/biomedicines10010017 - 23 Dec 2021

Cited by 15 | Viewed by 2898

Abstract

Although the antimicrobial potency of the pyrazole nucleus is widely reported, the antimicrobial effects of the 2-(4-bromo-3,5-diphenyl-pyrazol-1-yl)-ethanol (BBB4), found to be active against several other conditions, have never been investigated. Considering the worldwide need for new antimicrobial agents, we thought it noteworthy to assess the minimum inhibitory concentration (MICs) of BBB4 but, due to its scarce water-solubility, unequivocal determinations were tricky. To obtain more reliable MICs and to obtain a substance also potentially applicable in vivo, we recently prepared water-soluble, BBB4-loaded dendrimer nanoparticles (BBB4-G4K NPs), which proved to have physicochemical properties suitable for clinical application. Here, with the aim of developing a new antibacterial agent based on BBB4, the BBB4-G4K NPs were tested on several strains of different species of the Staphylococcus genus. Very low MICs (1.5–3.0 µM), 15.5–124.3-fold lower than those of the free BBB4, were observed against several isolates of S. aureus and S. epidermidis, the most pathogenic species of this genus, regardless of their resistance patterns to antibiotics. Aiming at hypothesizing a clinical use of BBB4-G4K NPs for staphylococcal skin infections, cytotoxicity experiments on human keratinocytes were performed; it was found that the nano-manipulated BBB4 released from BBB4-G4K NPs (LD₅₀ 138.6 µM) was 2.5-fold less cytotoxic than the untreated BBB4 (55.9 µM). Due to its physicochemical and biological properties, BBB4-G4K NPs could be considered as a promising novel therapeutic option against the very frequent staphylococcal skin infections. Full article

(This article belongs to the Special Issue Advances in Nanomaterials for Drug Delivery)

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Review

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29 pages, 3675 KiB

Open AccessReview

Carbon Graphitization: Towards Greener Alternatives to Develop Nanomaterials for Targeted Drug Delivery

by Davide Marin and Silvia Marchesan

Biomedicines 2022, 10(6), 1320; https://doi.org/10.3390/biomedicines10061320 - 4 Jun 2022

Cited by 2 | Viewed by 2885

Abstract

Carbon nanomaterials have attracted great interest for their unique physico-chemical properties for various applications, including medicine and, in particular, drug delivery, to solve the most challenging unmet clinical needs. Graphitization is a process that has become very popular for their production or modification. However, traditional conditions are energy-demanding; thus, recent efforts have been devoted to the development of greener routes that require lower temperatures or that use waste or byproducts as a carbon source in order to be more sustainable. In this concise review, we analyze the progress made in the last five years in this area, as well as in their development as drug delivery agents, focusing on active targeting, and conclude with a perspective on the future of the field. Full article

(This article belongs to the Special Issue Advances in Nanomaterials for Drug Delivery)

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35 pages, 1367 KiB

Open AccessReview

Current Development of Nano-Drug Delivery to Target Macrophages

by Donglin Cai, Wendong Gao, Zhelun Li, Yufeng Zhang, Lan Xiao and Yin Xiao

Biomedicines 2022, 10(5), 1203; https://doi.org/10.3390/biomedicines10051203 - 23 May 2022

Cited by 27 | Viewed by 6186

Abstract

Macrophages are the most important innate immune cells that participate in various inflammation-related diseases. Therefore, macrophage-related pathological processes are essential targets in the diagnosis and treatment of diseases. Since nanoparticles (NPs) can be preferentially taken up by macrophages, NPs have attracted most attention for specific macrophage-targeting. In this review, the interactions between NPs and the immune system are introduced to help understand the pharmacokinetics and biodistribution of NPs in immune cells. The current design and strategy of NPs modification for specific macrophage-targeting are investigated and summarized. Full article

(This article belongs to the Special Issue Advances in Nanomaterials for Drug Delivery)

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31 pages, 49644 KiB

Open AccessReview

Functionalized Liposome and Albumin-Based Systems as Carriers for Poorly Water-Soluble Anticancer Drugs: An Updated Review

by Sofia Teixeira, Maria Alice Carvalho and Elisabete M. S. Castanheira

Biomedicines 2022, 10(2), 486; https://doi.org/10.3390/biomedicines10020486 - 18 Feb 2022

Cited by 18 | Viewed by 4141

Abstract

Cancer is one of the leading causes of death worldwide. In the available treatments, chemotherapy is one of the most used, but has several associated problems, namely the high toxicity to normal cells and the resistance acquired by cancer cells to the therapeutic agents. The scientific community has been battling against this disease, developing new strategies and new potential chemotherapeutic agents. However, new drugs often exhibit poor solubility in water, which led researchers to develop functionalized nanosystems to carry and, specifically deliver, the drugs to cancer cells, targeting overexpressed receptors, proteins, and organelles. Thus, this review is focused on the recent developments of functionalized nanosystems used to carry poorly water-soluble drugs, with special emphasis on liposomes and albumin-based nanosystems, two major classes of organic nanocarriers with formulations already approved by the U.S. Food and Drug Administration (FDA) for cancer therapeutics. Full article

(This article belongs to the Special Issue Advances in Nanomaterials for Drug Delivery)

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