Special Issue "Nanopharmaceutics"

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

Deadline for manuscript submissions: closed (30 September 2020).

Special Issue Editor

Dr. Anton Naumov
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Guest Editor
Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX, USA
Interests: nanomaterials; fluorescence; nanotubes; graphene; quantum dots; biomedical imaging; near-infrared; cancer nanotechnology; drug delivery
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Nanomaterials have recently been utilized in a number of different applications in biotechnology, pioneering advances in the biomedical field through the areas of drug delivery, imaging, sensing, and tissue engineering. They have been demonstrated to substantially enhance treatment efficacy, protect healthy tissue from the adverse effects of toxic therapeutics, safely deliver degradable genetic medicines, target the therapies to the disease site, and serve as therapeutics on their own. Nanomaterials can be structurally adapted to a particular application and rendered biocompatible while facilitating the imaging and diagnostics of a variety of conditions. Such multifunctionality can address critical biomedical issues and enable novel advantageous pharmaceutic approaches.

This Special Issue of Nanomaterials aims to cover the latest advancements in the applications of nanomaterials in the development of pharmaceutical platforms and formulations for a variety of conditions. The scope of the issue includes drug and gene delivery, diagnostic or theranostic formulations, as well as nanomedicines.

Dr. Anton Naumov
Guest Editor

Manuscript Submission Information

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Keywords

Nanomaterials; drug delivery; drug transport; nanomedicine; imaging; targeting; photodynamic therapy; nanocomposite; fluorescence; MRI imaging; CT imaging; theranostic; nanosensor; nanoformulation; nanoparticles; nanorobotics; nanodiagnostics; nanobiotechnology

Published Papers (9 papers)

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Research

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Open AccessArticle
Effects of Doxorubicin Delivery by Nitrogen-Doped Graphene Quantum Dots on Cancer Cell Growth: Experimental Study and Mathematical Modeling
Nanomaterials 2021, 11(1), 140; https://doi.org/10.3390/nano11010140 - 08 Jan 2021
Abstract
With 18 million new cases diagnosed each year worldwide, cancer strongly impacts both science and society. Current models of cancer cell growth and therapeutic efficacy in vitro are time-dependent and often do not consider the Emax value (the maximum reduction in the [...] Read more.
With 18 million new cases diagnosed each year worldwide, cancer strongly impacts both science and society. Current models of cancer cell growth and therapeutic efficacy in vitro are time-dependent and often do not consider the Emax value (the maximum reduction in the growth rate), leading to inconsistencies in the obtained IC50 (concentration of the drug at half maximum effect). In this work, we introduce a new dual experimental/modeling approach to model HeLa and MCF-7 cancer cell growth and assess the efficacy of doxorubicin chemotherapeutics, whether alone or delivered by novel nitrogen-doped graphene quantum dots (N-GQDs). These biocompatible/biodegradable nanoparticles were used for the first time in this work for the delivery and fluorescence tracking of doxorubicin, ultimately decreasing its IC50 by over 1.5 and allowing for the use of up to 10 times lower doses of the drug to achieve the same therapeutic effect. Based on the experimental in vitro studies with nanomaterial-delivered chemotherapy, we also developed a method of cancer cell growth modeling that (1) includes an Emax value, which is often not characterized, and (2), most importantly, is measurement time-independent. This will allow for the more consistent assessment of the efficiency of anti-cancer drugs and nanomaterial-delivered formulations, as well as efficacy improvements of nanomaterial delivery. Full article
(This article belongs to the Special Issue Nanopharmaceutics)
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Open AccessArticle
Synthesis of Radioluminescent CaF2:Ln Core, Mesoporous Silica Shell Nanoparticles for Use in X-ray Based Theranostics
Nanomaterials 2020, 10(8), 1447; https://doi.org/10.3390/nano10081447 - 24 Jul 2020
Abstract
X-ray radiotherapy is a common method of treating cancerous tumors or other malignant lesions. The side effects of this treatment, however, can be deleterious to patient quality of life if critical tissues are affected. To potentially lower the effective doses of radiation and [...] Read more.
X-ray radiotherapy is a common method of treating cancerous tumors or other malignant lesions. The side effects of this treatment, however, can be deleterious to patient quality of life if critical tissues are affected. To potentially lower the effective doses of radiation and negative side-effects, new classes of nanoparticles are being developed to enhance reactive oxygen species production during irradiation. This report presents the synthesis and radiotherapeutic efficacy evaluation of a new nanoparticle formulation designed for this purpose, composed of a CaF2 core, mesoporous silica shell, and polyethylene glycol coating. The construct was additionally doped with Tb and Eu during the CaF2 core synthesis to prepare nanoparticles (NPs) with X-ray luminescent properties for potential application in fluorescence imaging. The mesoporous silica shell was added to provide the opportunity for small molecule loading, and the polyethylene glycol coating was added to impart aqueous solubility and biocompatibility. The potential of these nanomaterials to act as radiosensitizers for enhancing X-ray radiotherapy was supported by reactive oxygen species generation assays. Further, in vitro experiments indicate biocompatibility and enhanced cellular damage during X-ray radiotherapy. Full article
(This article belongs to the Special Issue Nanopharmaceutics)
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Open AccessArticle
Application of Nanopharmaceutics for Flibanserin Brain Delivery Augmentation Via the Nasal Route
Nanomaterials 2020, 10(7), 1270; https://doi.org/10.3390/nano10071270 - 29 Jun 2020
Abstract
Flibanserin (FLB) is a nonhormonal medicine approved by the Food and Drug Administration (FDA) to treat the hypoactive sexual appetite disorder in females. However, the peroral administration of the medicine is greatly affected by its poor bioavailability as a result of its extensive [...] Read more.
Flibanserin (FLB) is a nonhormonal medicine approved by the Food and Drug Administration (FDA) to treat the hypoactive sexual appetite disorder in females. However, the peroral administration of the medicine is greatly affected by its poor bioavailability as a result of its extensive first-pass effect and poor solubility. Aiming at circumventing these drawbacks, this work involves the formulation of optimized FLB transfersome (TRF) loaded intranasal hydrogel. Box–Behnken design was utilized for the improvement of FLB TRFs with decreased size. The FLB-to-phospholipid molar ratio, the edge activator hydrophilic lipophilic balance, and the pH of the hydration medium all exhibited significant effects on the TRF size. The optimized/developed TRFs were unilamellar in shape. Hydroxypropyl methyl cellulose based hydrogel filled with the optimized FLB TRFs exhibited an improved ex vivo permeation when compared with the control FLB-loaded hydrogel. In addition, the optimized TRF-loaded hydrogel exhibited higher bioavailability and enhanced brain delivery relative to the control hydrogel following intranasal administration in Wistar rats. The results foreshadow the possible potential application of the proposed intranasal optimized FLB-TRF-loaded hydrogel to increase the bioavailability and nose-to-brain delivery of the drug. Full article
(This article belongs to the Special Issue Nanopharmaceutics)
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Open AccessFeature PaperArticle
Effects of Nanoparticle Size and Radiation Energy on Copper-Cysteamine Nanoparticles for X-ray Induced Photodynamic Therapy
Nanomaterials 2020, 10(6), 1087; https://doi.org/10.3390/nano10061087 - 01 Jun 2020
Cited by 1
Abstract
The Copper-cysteamine (Cu-Cy) nanoparticle is a novel sensitizer with a potential to increase the effectiveness of radiation therapy for cancer treatment. In this work, the effect of nanoparticle size and the energy of X-rays on the effectiveness of radiation therapy are investigated. The [...] Read more.
The Copper-cysteamine (Cu-Cy) nanoparticle is a novel sensitizer with a potential to increase the effectiveness of radiation therapy for cancer treatment. In this work, the effect of nanoparticle size and the energy of X-rays on the effectiveness of radiation therapy are investigated. The effect of the particle size on their performance is very complicated. The nanoparticles with an average size of 300 nm have the most intense photoluminescence, the nanoparticles with the average size of 100 nm have the most reactive oxygen species production upon X-ray irradiation, while the nanoparticles with the average size of 40 nm have the best outcome in the tumor suppression in mice upon X-ray irradiation. For energy, 90 kVp radiation resulted in smaller tumor sizes than 250 kVp or 350 kVp radiation energies. Overall, knowledge of the effect of nanoparticle size and radiation energy on radiation therapy outcomes could be useful for future applications of Cu-Cy nanoparticles. Full article
(This article belongs to the Special Issue Nanopharmaceutics)
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Open AccessArticle
High Density Display of an Anti-Angiogenic Peptide on Micelle Surfaces Enhances Their Inhibition of αvβ3 Integrin-Mediated Neovascularization In Vitro
Nanomaterials 2020, 10(3), 581; https://doi.org/10.3390/nano10030581 - 22 Mar 2020
Cited by 1
Abstract
Diabetic retinopathy (DR), Retinopathy of Pre-maturity (ROP), and Age-related Macular Degeneration (AMD) are multifactorial manifestations associated with abnormal growth of blood vessels in the retina. These three diseases account for 5% of the total blindness and vision impairment in the US alone. The [...] Read more.
Diabetic retinopathy (DR), Retinopathy of Pre-maturity (ROP), and Age-related Macular Degeneration (AMD) are multifactorial manifestations associated with abnormal growth of blood vessels in the retina. These three diseases account for 5% of the total blindness and vision impairment in the US alone. The current treatment options involve heavily invasive techniques such as frequent intravitreal administration of anti-VEGF (vascular endothelial growth factor) antibodies, which pose serious risks of endophthalmitis, retinal detachment and a multitude of adverse effects stemming from the diverse physiological processes that involve VEGF. To overcome these limitations, this current study utilizes a micellar delivery vehicle (MC) decorated with an anti-angiogenic peptide (aANGP) that inhibits αvβ3 mediated neovascularization using primary endothelial cells (HUVEC). Stable incorporation of the peptide into the micelles (aANGP-MCs) for high valency surface display was achieved with a lipidated peptide construct. After 24 h of treatment, aANGP-MCs showed significantly higher inhibition of proliferation and migration compared to free from aANGP peptide. A tube formation assay clearly demonstrated a dose-dependent angiogenic inhibitory effect of aANGP-MCs with a maximum inhibition at 4 μg/mL, a 1000-fold lower concentration than that required for free from aANGP to display a biological effect. These results demonstrate valency-dependent enhancement in the therapeutic efficacy of a bioactive peptide following conjugation to nanoparticle surfaces and present a possible treatment alternative to anti-VEGF antibody therapy with decreased side effects and more versatile options for controlled delivery. Full article
(This article belongs to the Special Issue Nanopharmaceutics)
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Open AccessArticle
In Vivo Biodistribution of Respirable Solid Lipid Nanoparticles Surface-Decorated with a Mannose-Based Surfactant: A Promising Tool for Pulmonary Tuberculosis Treatment?
Nanomaterials 2020, 10(3), 568; https://doi.org/10.3390/nano10030568 - 21 Mar 2020
Cited by 3
Abstract
The active targeting to alveolar macrophages (AM) is an attractive strategy to improve the therapeutic efficacy of ‘old’ drugs currently used in clinical practice for the treatment of pulmonary tuberculosis. Previous studies highlighted the ability of respirable solid lipid nanoparticle assemblies (SLNas), loaded [...] Read more.
The active targeting to alveolar macrophages (AM) is an attractive strategy to improve the therapeutic efficacy of ‘old’ drugs currently used in clinical practice for the treatment of pulmonary tuberculosis. Previous studies highlighted the ability of respirable solid lipid nanoparticle assemblies (SLNas), loaded with rifampicin (RIF) and functionalized with a novel synthesized mannose-based surfactant (MS), both alone and in a blend with sodium taurocholate, to efficiently target the AM via mannose receptor-mediated mechanism. Here, we present the in vivo biodistribution of these mannosylated SLNas, in comparison with the behavior of both non-functionalized SLNas and bare RIF. SLNas biodistribution was assessed, after intratracheal instillation in mice, by whole-body real-time fluorescence imaging in living animals and RIF quantification in excised organs and plasma. Additionally, SLNas cell uptake was determined by using fluorescence microscopy on AM from bronchoalveolar lavage fluid and alveolar epithelium from lung dissections. Finally, histopathological evaluation was performed on lungs 24 h after administration. SLNas functionalized with MS alone generated the highest retention in lungs associated with a poor spreading in extra-pulmonary regions. This effect could be probably due to a greater AM phagocytosis with respect to SLNas devoid of mannose on their surface. The results obtained pointed out the unique ability of the nanoparticle surface decoration to provide a potential more efficient treatment restricted to the lungs where the primary tuberculosis infection is located. Full article
(This article belongs to the Special Issue Nanopharmaceutics)
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Open AccessArticle
Single-Walled Carbon Nanotube-Assisted Antibiotic Delivery and Imaging in S. epidermidis Strains Addressing Antibiotic Resistance
Nanomaterials 2019, 9(12), 1685; https://doi.org/10.3390/nano9121685 - 25 Nov 2019
Cited by 5
Abstract
Although conventional antibiotics have evolved as a staple of modern medicine, increasing antibiotic resistance and the lack of antibiotic efficacy against new bacterial threats is becoming a major medical threat. In this work, we employ single-walled carbon nanotubes (SWCNTs) known to deliver and [...] Read more.
Although conventional antibiotics have evolved as a staple of modern medicine, increasing antibiotic resistance and the lack of antibiotic efficacy against new bacterial threats is becoming a major medical threat. In this work, we employ single-walled carbon nanotubes (SWCNTs) known to deliver and track therapeutics in mammalian cells via intrinsic near-infrared fluorescence as carriers enhancing antibacterial delivery of doxycycline and methicillin. SWCNTs dispersed in water by antibiotics without the use of toxic bile salt surfactants facilitate efficacy enhancement for both antibiotics against Staphylococcus epidermidis strain showing minimal sensitivity to methicillin. Doxycycline to which the strain did not show resistance in complex with SWCNTs provides only minor increase in efficacy, whereas the SWCNTs/methicillin complex yields up to 40-fold efficacy enhancement over antibiotics alone, suggesting that SWCNT-assisted delivery may circumvent antibiotic resistance in that bacterial strain. At the same time SWCNT/antibiotic formulations appear to be less toxic to mammalian cells than antibiotics alone suggesting that nanomaterial platforms may not restrict potential biomedical applications. The improvement in antibacterial performance with SWCNT delivery is tested via 3 independent assays—colony count, MIC (Minimal Inhibitory Concentration) turbidity and disk diffusion, with the statistical significance of the latter verified by ANOVA and Dunnett’s method. The potential mechanism of action is attributed to SWCNT interactions with bacterial cell wall and adherence to the membrane, as substantial association of SWCNT with bacteria is observed—the near-infrared fluorescence microscopy of treated bacteria shows localization of SWCNT fluorescence in bacterial clusters, scanning electron microscopy verifies SWCNT association with bacterial surface, whereas transmission electron microscopy shows individual SWCNT penetration into bacterial cell wall. This work characterizes SWCNTs as novel advantageous antibiotic delivery/imaging agents having the potential to address antibiotic resistance. Full article
(This article belongs to the Special Issue Nanopharmaceutics)
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Open AccessArticle
Medium-Dependent Antibacterial Properties and Bacterial Filtration Ability of Reduced Graphene Oxide
Nanomaterials 2019, 9(10), 1454; https://doi.org/10.3390/nano9101454 - 13 Oct 2019
Cited by 2
Abstract
Toxicity of reduced graphene oxide (rGO) has been a topic of multiple studies and was shown to depend on a variety of characteristics of rGO and biological objects of interest. In this paper, we demonstrate that when studying the same dispersions of rGO [...] Read more.
Toxicity of reduced graphene oxide (rGO) has been a topic of multiple studies and was shown to depend on a variety of characteristics of rGO and biological objects of interest. In this paper, we demonstrate that when studying the same dispersions of rGO and fluorescent Escherichia coli (E. coli) bacteria, the outcome of nanotoxicity experiments also depends on the type of culture medium. We show that rGO inhibits the growth of bacteria in a nutrition medium but shows little effect on the behavior of E. coli in a physiological saline solution. The observed effects of rGO on E. coli in different media could be at least partially rationalized through the adsorption of bacteria and nutrients on the dispersed rGO sheets, which is likely mediated via hydrogen bonding. We also found that the interaction between rGO and E. coli is medium-dependent, and in physiological saline solutions they form stable flocculate structures that were not observed in nutrition media. Furthermore, the aggregation of rGO and E. coli in saline media was observed regardless of whether the bacteria were alive or dead. Filtration of the aggregate suspensions led to nearly complete removal of bacteria from filtered liquids, which highlights the potential of rGO for the filtration and separation of biological contaminants, regardless of whether they include live or dead microorganisms. Full article
(This article belongs to the Special Issue Nanopharmaceutics)
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Review

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Open AccessReview
Nanopharmaceutics: Part II—Production Scales and Clinically Compliant Production Methods
Nanomaterials 2020, 10(3), 455; https://doi.org/10.3390/nano10030455 - 04 Mar 2020
Cited by 16
Abstract
Due the implementation of nanotechnologies in the pharmaceutical industry over the last few decades, new type of cutting-edge formulations—nanopharmaceutics—have been proposed. These comprise pharmaceutical products at the nanoscale, developed from different types of materials with the purpose to, e.g., overcome solubility problems of [...] Read more.
Due the implementation of nanotechnologies in the pharmaceutical industry over the last few decades, new type of cutting-edge formulations—nanopharmaceutics—have been proposed. These comprise pharmaceutical products at the nanoscale, developed from different types of materials with the purpose to, e.g., overcome solubility problems of poorly water-soluble drugs, the pharmacokinetic and pharmacodynamic profiles of known drugs but also of new biomolecules, to modify the release profile of loaded compounds, or to decrease the risk of toxicity by providing site-specific delivery reducing the systemic distribution and thus adverse side effects. To succeed with the development of a nanopharmaceutical formulation, it is first necessary to analyze the type of drug which is to be encapsulated, select the type matrix to load it (e.g., polymers, lipids, polysaccharides, proteins, metals), followed by the production procedure. Together these elements have to be compatible with the administration route. To be launched onto the market, the selected production method has to be scaled-up, and quality assurance implemented for the product to reach clinical trials, during which in vivo performance is evaluated. Regulatory issues concerning nanopharmaceutics still require expertise for harmonizing legislation and a clear understanding of clinically compliant production methods. The first part of this study addressing “Nanopharmaceutics: Part I—Clinical trials legislation and Good Manufacturing Practices (GMP) of nanotherapeutics in the EU” has been published in Pharmaceutics. This second part complements the study with the discussion about the production scales and clinically compliant production methods of nanopharmaceutics. Full article
(This article belongs to the Special Issue Nanopharmaceutics)
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