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Nanotechnology in Targeted Drug Delivery
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Nanotechnology in Targeted Drug Delivery

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 42303

Special Issue Editor

Prof. Dr. Antonio Di Stefano

E-Mail Website
Guest Editor
Department of Pharmacy, University G. d’Annunzio, Via dei Vestini, 66100 Chieti, Italy
Interests: drug delivery systems; CNS drug delivery; neurodegenerative disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The application of nonotechnology has aroused interest to improve the effectiveness of therapies for a variety of diseases difficult to treat in a conventional way. In this context, nanostructured materials have been proposed as suitable approach employed in the drug delivery to cross physiological barriers, thus increasing bioavailability, biodistribution, and accumulation of therapeutics preferentially in the target diseased area, acting as stability enhancers. Furthermore it is interesting their increasing application in various biomedical fields such as tissue engineering, and medical diagnosis. Starting from these evidences, this Special Issue aims to highlight the latest achievements and current progresses useful to implement the scientific knowledge in the field of targeted drug delivery. For this purpose, we encourage scientists from worldwide to present their work as scientific contribution or review articles. We will really appreciate your valuable contributions and it will be a pleasure to collect them.

Prof. Dr. Antonio Di Stefano
Guest Editor

Manuscript Submission Information

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Keywords

  • pharmaceutical materials
  • functionalization
  • nanoformulations
  • drug release

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Related Special Issue

Published Papers (11 papers)

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Editorial

Jump to: Research, Review

2 pages, 166 KiB  
Editorial
Nanotechnology in Targeted Drug Delivery
by Antonio Di Stefano
Int. J. Mol. Sci. 2023, 24(9), 8194; https://doi.org/10.3390/ijms24098194 - 3 May 2023
Cited by 19 | Viewed by 2278
Abstract
The use of large sized materials in drug delivery raises several challenges, including in vivo stability, poor bioavailability/solubility/absorption, and issues with target-specific delivery, in addition to the side effects of the delivered drugs [...] Full article
(This article belongs to the Special Issue Nanotechnology in Targeted Drug Delivery)

Research

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15 pages, 3583 KiB  
Article
Mathematical Optimisation of Magnetic Nanoparticle Diffusion in the Brain White Matter
by Tian Yuan, Yi Yang, Wenbo Zhan and Daniele Dini
Int. J. Mol. Sci. 2023, 24(3), 2534; https://doi.org/10.3390/ijms24032534 - 28 Jan 2023
Cited by 11 | Viewed by 2342
Abstract
Magnetic nanoparticles (MNPs) are a promising drug delivery system to treat brain diseases, as the particle transport trajectory can be manipulated by an external magnetic field. However, due to the complex microstructure of brain tissues, particularly the arrangement of nerve fibres in the [...] Read more.
Magnetic nanoparticles (MNPs) are a promising drug delivery system to treat brain diseases, as the particle transport trajectory can be manipulated by an external magnetic field. However, due to the complex microstructure of brain tissues, particularly the arrangement of nerve fibres in the white matter (WM), how to achieve desired drug distribution patterns, e.g., uniform distribution, is largely unknown. In this study, by adopting a mathematical model capable of capturing the diffusion trajectories of MNPs, we conducted a pilot study to investigate the effects of key parameters in the MNP delivery on the particle diffusion behaviours in the brain WM microstructures. The results show that (i) a uniform distribution of MNPs can be achieved in anisotropic tissues by adjusting the particle size and magnetic field; (ii) particle size plays a key role in determining MNPs’ diffusion behaviours. The magnitude of MNP equivalent diffusivity is reversely correlated to the particle size. The MNPs with a dimension greater than 90 nm cannot reach a uniform distribution in the brain WM even in an external magnitude field; (iii) axon tortuosity may lead to transversely anisotropic MNP transport in the brain WM; however, this effect can be mitigated by applying an external magnetic field perpendicular to the local axon track. This study not only advances understanding to answer the question of how to optimise MNP delivery, but also demonstrates the potential of mathematical modelling to help achieve desired drug distributions in biological tissues with a complex microstructure. Full article
(This article belongs to the Special Issue Nanotechnology in Targeted Drug Delivery)
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17 pages, 3846 KiB  
Article
Bottom-Up Strategy to Forecast the Drug Location and Release Kinetics in Antitumoral Electrospun Drug Delivery Systems
by Raffaele Longo, Marialuigia Raimondo, Luigi Vertuccio, Maria Camilla Ciardulli, Marco Sirignano, Annaluisa Mariconda, Giovanna Della Porta and Liberata Guadagno
Int. J. Mol. Sci. 2023, 24(2), 1507; https://doi.org/10.3390/ijms24021507 - 12 Jan 2023
Cited by 7 | Viewed by 1978
Abstract
Electrospun systems are becoming promising devices usable for topical treatments. They are eligible to deliver different therapies, from anti-inflammatory to antitumoral. In the current research, polycaprolactone electrospun membranes loaded with synthetic and commercial antitumoral active substances were produced, underlining how the matrix-filler affinity [...] Read more.
Electrospun systems are becoming promising devices usable for topical treatments. They are eligible to deliver different therapies, from anti-inflammatory to antitumoral. In the current research, polycaprolactone electrospun membranes loaded with synthetic and commercial antitumoral active substances were produced, underlining how the matrix-filler affinity is a crucial parameter for designing drug delivery devices. Nanofibrous membranes loaded with different percentages of Dacarbazine (the drug of choice for melanoma) and a synthetic derivative of Dacarbazine were produced and compared to membranes loaded with AuM1, a highly active Au-complex with low affinity to the matrix. AFM morphologies showed that the surface profile of nanofibers loaded with affine substances is similar to one of the unloaded systems, thanks to the nature of the matrix-filler interaction. FTIR analyses proved the efficacy of the interaction between the amidic group of the Dacarbazine and the polycaprolactone. In AuM1-loaded membranes, because of the weak matrix-filler interaction, the complex is mainly aggregated in nanometric domains on the nanofiber surface, which manifests a nanometric roughness. Consequently, the release profiles follow a Fickian behavior for the Dacarbazine-based systems, whereas a two-step with a highly prominent burst effect was observed for AuM1 systems. The performed antitumoral tests evidence the high-cytotoxic activity of the electrospun systems against melanoma cell lines, proving that the synthetic substances are more active than the commercial dacarbazine. Full article
(This article belongs to the Special Issue Nanotechnology in Targeted Drug Delivery)
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19 pages, 2768 KiB  
Article
The Impact of Nanobody Density on the Targeting Efficiency of PEGylated Liposomes
by Bárbara S. Mesquita, Marcel H. A. M. Fens, Alessia Di Maggio, Esmeralda D. C. Bosman, Wim E. Hennink, Michal Heger and Sabrina Oliveira
Int. J. Mol. Sci. 2022, 23(23), 14974; https://doi.org/10.3390/ijms232314974 - 29 Nov 2022
Cited by 9 | Viewed by 2973
Abstract
Nanoparticles (NPs) are commonly modified with tumor-targeting moieties that recognize proteins overexpressed on the extracellular membrane to increase their specific interaction with target cells. Nanobodies (Nbs), the variable domain of heavy chain-only antibodies, are a robust targeting ligand due to their small size, [...] Read more.
Nanoparticles (NPs) are commonly modified with tumor-targeting moieties that recognize proteins overexpressed on the extracellular membrane to increase their specific interaction with target cells. Nanobodies (Nbs), the variable domain of heavy chain-only antibodies, are a robust targeting ligand due to their small size, superior stability, and strong binding affinity. For the clinical translation of targeted Nb-NPs, it is essential to understand how the number of Nbs per NP impacts the receptor recognition on cells. To study this, Nbs targeting the hepatocyte growth factor receptor (MET-Nbs) were conjugated to PEGylated liposomes at a density from 20 to 800 per liposome and their targeting efficiency was evaluated in vitro. MET-targeted liposomes (MET-TLs) associated more profoundly with MET-expressing cells than non-targeted liposomes (NTLs). MET-TLs with approximately 150–300 Nbs per liposome exhibited the highest association and specificity towards MET-expressing cells and retained their targeting capacity when pre-incubated with proteins from different sources. Furthermore, a MET-Nb density above 300 Nbs per liposome increased the interaction of MET-TLs with phagocytic cells by 2-fold in ex vivo human blood compared to NTLs. Overall, this study demonstrates that adjusting the MET-Nb density can increase the specificity of NPs towards their intended cellular target and reduce NP interaction with phagocytic cells. Full article
(This article belongs to the Special Issue Nanotechnology in Targeted Drug Delivery)
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17 pages, 1914 KiB  
Article
Non-Ionic Surfactant Effects on Innate Pluronic 188 Behavior: Interactions, and Physicochemical and Biocompatibility Studies
by Orestis Kontogiannis, Dimitrios Selianitis, Diego Romano Perinelli, Giulia Bonacucina, Natassa Pippa, Maria Gazouli and Stergios Pispas
Int. J. Mol. Sci. 2022, 23(22), 13814; https://doi.org/10.3390/ijms232213814 - 10 Nov 2022
Cited by 16 | Viewed by 2380
Abstract
The aim of this research was to prepare novel block copolymer-surfactant hybrid nanosystems using the triblock copolymer Pluronic 188, along with surfactants of different hydrophilic to lipophilic balance (HLB ratio—which indicates the degree to which a surfactant is hydrophilic or hydrophobic) and thermotropic [...] Read more.
The aim of this research was to prepare novel block copolymer-surfactant hybrid nanosystems using the triblock copolymer Pluronic 188, along with surfactants of different hydrophilic to lipophilic balance (HLB ratio—which indicates the degree to which a surfactant is hydrophilic or hydrophobic) and thermotropic behavior. The surfactants used were of non-ionic nature, of which Tween 80® and Brij 58® were more hydrophilic, while Span 40® and Span 60® were more hydrophobic. Each surfactant has unique innate thermal properties and an affinity towards Pluronic 188. The nanosystems were formulated through mixing the pluronic with the surfactants at three different ratios, namely 90:10, 80:20, and 50:50, using the thin-film hydration technique and keeping the pluronic concentration constant. The physicochemical characteristics of the prepared nanosystems were evaluated using various light scattering techniques, while their thermotropic behavior was characterized via microDSC and high-resolution ultrasound spectroscopy. Microenvironmental parameters were attained through the use of fluorescence spectroscopy, while the cytotoxicity of the nanocarriers was studied in vitro. The results indicate that the combination of Pluronic 188 with the above surfactants was able to produce hybrid homogeneous nanoparticle populations of adequately small diameters. The different surfactants had a clear effect on physicochemical parameters such as the size, hydrodynamic diameter, and polydispersity index of the final formulation. The mixing of surfactants with the pluronic clearly changed its thermotropic behavior and thermal transition temperature (Tm) and highlighted the specific interactions that occurred between the different materials, as well as the effect of increasing the surfactant concentration on inherent polymer characteristics and behavior. The formulated nanosystems were found to be mostly of minimal toxicity. The obtained results demonstrate that the thin-film hydration method can be used for the formulation of pluronic-surfactant hybrid nanoparticles, which in turn exhibit favorable characteristics in terms of their possible use in drug delivery applications. This investigation can be used as a road map for the selection of an appropriate nanosystem as a novel vehicle for drug delivery. Full article
(This article belongs to the Special Issue Nanotechnology in Targeted Drug Delivery)
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18 pages, 5040 KiB  
Article
Naked and Decorated Nanoparticles Containing H2S-Releasing Doxorubicin: Preparation, Characterization and Assessment of Their Antitumoral Efficiency on Various Resistant Tumor Cells
by Elena Peira, Daniela Chirio, Simona Sapino, Konstantin Chegaev, Giulia Chindamo, Iris Chiara Salaroglio, Chiara Riganti and Marina Gallarate
Int. J. Mol. Sci. 2022, 23(19), 11555; https://doi.org/10.3390/ijms231911555 - 30 Sep 2022
Cited by 5 | Viewed by 1911
Abstract
Several semisynthetic, low-cardiotoxicity doxorubicin (DOXO) conjugated have been extensively described, considering the risk of cytotoxicity loss against resistant tumor cells, which mainly present drug efflux capacity. Doxorubicin 14-[4-(4-phenyl-5-thioxo-5H-[1,2]dithiol-3-yl)]-benzoate (H2S-DOXO) was synthetized and tested for its ability to overcome drug resistance with [...] Read more.
Several semisynthetic, low-cardiotoxicity doxorubicin (DOXO) conjugated have been extensively described, considering the risk of cytotoxicity loss against resistant tumor cells, which mainly present drug efflux capacity. Doxorubicin 14-[4-(4-phenyl-5-thioxo-5H-[1,2]dithiol-3-yl)]-benzoate (H2S-DOXO) was synthetized and tested for its ability to overcome drug resistance with good intracellular accumulation. In this paper, we present a formulation study aimed to develop naked and decorated H2S-DOXO-loaded lipid nanoparticles (NPs). NPs prepared by the “cold dilution of microemulsion” method were decorated with hyaluronic acid (HA) to obtain active targeting and characterized for their physicochemical properties, drug entrapment efficiency, long-term stability, and in vitro drug release. Best formulations were tested in vitro on human-sensitive (MCF7) and human/mouse DOXO-resistant (MDA-MDB -231 and JC) breast cancer cells, on human (U-2OS) osteosarcoma cells and DOXO-resistant human/mouse osteosarcoma cells (U-2OS/DX580/K7M2). HA-decoration by HA-cetyltrimethyl ammonium bromide electrostatic interaction on NPs surface was confirmed by Zeta potential and elemental analysis at TEM. NPs had mean diameters lower than 300 nm, 70% H2S-DOXO entrapment efficiency, and were stable for almost 28 days. HA-decorated NPs accumulated H2S-DOXO in Pgp-expressing cells reducing cell viability. HA-decorated NPs result in the best formulation to increase the inter-cellular H2S-DOXO delivery and kill resistant cells, and therefore, as a future perspective, they will be taken into account for further in vivo experiments on tumor animal model. Full article
(This article belongs to the Special Issue Nanotechnology in Targeted Drug Delivery)
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12 pages, 1657 KiB  
Article
Ab Initio Insight into the Interaction of Metal-Decorated Fluorinated Carbon Fullerenes with Anti-COVID Drugs
by Konstantin P. Katin, Alexey I. Kochaev, Savas Kaya, Fadoua El-Hajjaji and Mikhail M. Maslov
Int. J. Mol. Sci. 2022, 23(4), 2345; https://doi.org/10.3390/ijms23042345 - 21 Feb 2022
Cited by 8 | Viewed by 2531
Abstract
We theoretically investigated the adsorption of two common anti-COVID drugs, favipiravir and chloroquine, on fluorinated C60 fullerene, decorated with metal ions Cr3+, Fe2+, Fe3+, Ni2+. We focused on the effect of fluoridation on the [...] Read more.
We theoretically investigated the adsorption of two common anti-COVID drugs, favipiravir and chloroquine, on fluorinated C60 fullerene, decorated with metal ions Cr3+, Fe2+, Fe3+, Ni2+. We focused on the effect of fluoridation on the interaction of fullerene with metal ions and drugs in an aqueous solution. We considered three model systems, C60, C60F2 and C60F48, and represented pristine, low-fluorinated and high-fluorinated fullerenes, respectively. Adsorption energies, deformation of fullerene and drug molecules, frontier molecular orbitals and vibrational spectra were investigated in detail. We found that different drugs and different ions interacted differently with fluorinated fullerenes. Cr3+ and Fe2+ ions lead to the defluorination of low-fluorinated fullerenes. Favipiravir also leads to their defluorination with the formation of HF molecules. Therefore, fluorinated fullerenes are not suitable for the delivery of favipiravir and similar drugs molecules. In contrast, we found that fluorine enhances the adsorption of Ni2+ and Fe3+ ions on fullerene and their activity to chloroquine. Ni2+-decorated fluorinated fullerenes were found to be stable and suitable carriers for the loading of chloroquine. Clear shifts of infrared, ultraviolet and visible spectra can provide control over the loading of chloroquine on Ni2+-doped fluorinated fullerenes. Full article
(This article belongs to the Special Issue Nanotechnology in Targeted Drug Delivery)
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15 pages, 2206 KiB  
Article
An Engineered Nanocomplex with Photodynamic and Photothermal Synergistic Properties for Cancer Treatment
by Eli Varon, Gaddi Blumrosen, Moshe Sinvani, Elina Haimov, Shlomi Polani, Michal Natan, Irit Shoval, Avi Jacob, Ayelet Atkins, David Zitoun and Orit Shefi
Int. J. Mol. Sci. 2022, 23(4), 2286; https://doi.org/10.3390/ijms23042286 - 18 Feb 2022
Cited by 12 | Viewed by 3951
Abstract
Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising therapeutic methods for cancer treatment; however, as single modality therapies, either PDT or PTT is still limited in its success rate. A dual application of both PDT and PTT, in a combined protocol, has [...] Read more.
Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising therapeutic methods for cancer treatment; however, as single modality therapies, either PDT or PTT is still limited in its success rate. A dual application of both PDT and PTT, in a combined protocol, has gained immense interest. In this study, gold nanoparticles (AuNPs) were conjugated with a PDT agent, meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer, designed as nanotherapeutic agents that can activate a dual photodynamic/photothermal therapy in SH-SY5Y human neuroblastoma cells. The AuNP-mTHPC complex is biocompatible, soluble, and photostable. PDT efficiency is high because of immediate reactive oxygen species (ROS) production upon mTHPC activation by the 650-nm laser, which decreased mitochondrial membrane potential (∆ψm). Likewise, the AuNP-mTHPC complex is used as a photoabsorbing (PTA) agent for PTT, due to efficient plasmon absorption and excellent photothermal conversion characteristics of AuNPs under laser irradiation at 532 nm. Under the laser irradiation of a PDT/PTT combination, a twofold phototoxicity outcome follows, compared to PDT-only or PTT-only treatment. This indicates that PDT and PTT have synergistic effects together as a combined therapeutic method. Our study aimed at applying the AuNP-mTHPC approach as a potential treatment of cancer in the biomedical field. Full article
(This article belongs to the Special Issue Nanotechnology in Targeted Drug Delivery)
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12 pages, 2475 KiB  
Article
Stimuli-Responsive Drug Delivery of Doxorubicin Using Magnetic Nanoparticle Conjugated Poly(ethylene glycol)-g-Chitosan Copolymer
by Hyun-Min Yoon, Min-Su Kang, Go-Eun Choi, Young-Joon Kim, Chang-Hyu Bae, Young-Bob Yu and Young-IL Jeong
Int. J. Mol. Sci. 2021, 22(23), 13169; https://doi.org/10.3390/ijms222313169 - 6 Dec 2021
Cited by 24 | Viewed by 3080
Abstract
Stimuli-responsive nanoparticles are regarded as an ideal candidate for anticancer drug targeting. We synthesized glutathione (GSH) and magnetic-sensitive nanocomposites for a dual-targeting strategy. To achieve this goal, methoxy poly (ethylene glycol) (MePEG) was grafted to water-soluble chitosan (abbreviated as ChitoPEG). Then doxorubicin (DOX) [...] Read more.
Stimuli-responsive nanoparticles are regarded as an ideal candidate for anticancer drug targeting. We synthesized glutathione (GSH) and magnetic-sensitive nanocomposites for a dual-targeting strategy. To achieve this goal, methoxy poly (ethylene glycol) (MePEG) was grafted to water-soluble chitosan (abbreviated as ChitoPEG). Then doxorubicin (DOX) was conjugated to the backbone of chitosan via disulfide linkage. Iron oxide (IO) magnetic nanoparticles were also conjugated to the backbone of chitosan to provide magnetic sensitivity. In morphological observation, images from a transmission electron microscope (TEM) showed that IO nanoparticles were embedded in the ChitoPEG/DOX/IO nanocomposites. In a drug release study, GSH addition accelerated DOX release rate from nanocomposites, indicating that nanocomposites have redox-responsiveness. Furthermore, external magnetic stimulus concentrated nanocomposites in the magnetic field and then provided efficient internalization of nanocomposites into cancer cells in cell culture experiments. In an animal study with CT26 cell-bearing mice, nanocomposites showed superior magnetic sensitivity and then preferentially targeted tumor tissues in the field of external magnetic stimulus. Nanocomposites composed of ChitoPEG/DOX/IO nanoparticle conjugates have excellent anticancer drug targeting properties. Full article
(This article belongs to the Special Issue Nanotechnology in Targeted Drug Delivery)
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Review

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25 pages, 1385 KiB  
Review
Melissa officinalis: Composition, Pharmacological Effects and Derived Release Systems—A Review
by Gabriela Petrisor, Ludmila Motelica, Luminita Narcisa Craciun, Ovidiu Cristian Oprea, Denisa Ficai and Anton Ficai
Int. J. Mol. Sci. 2022, 23(7), 3591; https://doi.org/10.3390/ijms23073591 - 25 Mar 2022
Cited by 58 | Viewed by 13569
Abstract
Melissa officinalis is a medicinal plant rich in biologically active compounds which is used worldwide for its therapeutic effects. Chemical studies on its composition have shown that it contains mainly flavonoids, terpenoids, phenolic acids, tannins, and essential oil. The main active constituents of [...] Read more.
Melissa officinalis is a medicinal plant rich in biologically active compounds which is used worldwide for its therapeutic effects. Chemical studies on its composition have shown that it contains mainly flavonoids, terpenoids, phenolic acids, tannins, and essential oil. The main active constituents of Melissa officinalis are volatile compounds (geranial, neral, citronellal and geraniol), triterpenes (ursolic acid and oleanolic acid), phenolic acids (rosmarinic acid, caffeic acid and chlorogenic acid), and flavonoids (quercetin, rhamnocitrin, and luteolin). According to the biological studies, the essential oil and extracts of Melissa officinalis have active compounds that determine many pharmacological effects with potential medical uses. A new field of research has led to the development of controlled release systems with active substances from plants. Therefore, the essential oil or extract of Melissa officinalis has become a major target to be incorporated into various controlled release systems which allow a sustained delivery. Full article
(This article belongs to the Special Issue Nanotechnology in Targeted Drug Delivery)
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22 pages, 1212 KiB  
Review
Nanoparticle-Mediated Delivery Systems in Photodynamic Therapy of Colorectal Cancer
by Nokuphila Winifred Nompumelelo Simelane and Heidi Abrahamse
Int. J. Mol. Sci. 2021, 22(22), 12405; https://doi.org/10.3390/ijms222212405 - 17 Nov 2021
Cited by 28 | Viewed by 3544
Abstract
Colorectal cancer (CRC) involving a malignant tumour remains one of the greatest contributing causes of fatal mortality and has become the third globally ranked malignancy in terms of cancer-associated deaths. Conventional CRC treatment approaches such as surgery, radiation, and chemotherapy are the most [...] Read more.
Colorectal cancer (CRC) involving a malignant tumour remains one of the greatest contributing causes of fatal mortality and has become the third globally ranked malignancy in terms of cancer-associated deaths. Conventional CRC treatment approaches such as surgery, radiation, and chemotherapy are the most utilized approaches to treat this disease. However, they are limited by low selectivity and systemic toxicity, so they cannot completely eradicate this disease. Photodynamic therapy (PDT) is an emerging therapeutic modality that exerts selective cytotoxicity to cancerous cells through the activation of photosensitizers (PSs) under light irradiation to produce cytotoxic reactive oxygen species (ROS), which then cause cancer cell death. Cumulative research findings have highlighted the significant role of traditional PDT in CRC treatment; however, the therapeutic efficacy of the classical PDT strategy is restricted due to skin photosensitivity, poor cancerous tissue specificity, and limited penetration of light. The application of nanoparticles in PDT can mitigate some of these shortcomings and enhance the targeting ability of PS in order to effectively use PDT against CRC as well as to reduce systemic side effects. Although 2D culture models are widely used in cancer research, they have some limitations. Therefore, 3D models in CRC PDT, particularly multicellular tumour spheroids (MCTS), have attracted researchers. This review summarizes several photosensitizers that are currently used in CRC PDT and gives an overview of recent advances in nanoparticle application for enhanced CRC PDT. In addition, the progress of 3D-model applications in CRC PDT is discussed. Full article
(This article belongs to the Special Issue Nanotechnology in Targeted Drug Delivery)
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