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Special Issue "Surface-Functionalized Nanoparticles as Drug Carriers"

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

Deadline for manuscript submissions: closed (25 September 2019).

Special Issue Editors

Prof. Dr. Jagdish Singh
E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, College of Health Professions, North Dakota State University, Fargo, ND 58108-6050, USA
Interests: Mechanistic studies for developing and testing novel delivery technologies to deliver biotechnologically derived molecules (e.g., peptide, protein, and gene). The specific research interests are: gene delivery to prevent and treat neurodegenerative disorders, using nanotechnology; delivery of anticancer drugs to the brain for the treatment of brain tumors using bi-ligand (transferrin and cell-penetrating peptides) tethered liposomes; synthesis and characterization of biomaterials for gene and protein delivery for the treatment of diabetes, osteoporosis, and neurodegenerative diseases; fatty acid/amino acid and cell-penetrating peptide grafted chitosan-based nanomicelles for the delivery of pDNA encoding IL-4 and IL-10 for the prevention of type 1 diabetes; cationic nanomicelles for the delivery of DNA vaccines
Special Issues and Collections in MDPI journals
Dr. Buddhadev Layek
E-Mail Website
Guest Editor
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard St. SE, Room 9-153 WDH, Minneapolis, MN 55455, USA
Interests: drug and gene delivery; nanomedicine; biomaterials; pharmacokinetics; stem cells
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

With their unique physicochemical properties and nanoscale effects, nanoparticles can modulate the basic properties and bioactivity of drugs. These features make them attractive tools for diverse biomedical applications, especially in the field of drug delivery. Over the decades, nanocarriers have been extensively investigated for improved pharmacokinetics and biodistribution, increased stability, reduced toxicities, controlled release, and site-specific delivery of therapeutics. However, the efficacy of nanocarrier-based drug delivery systems is largely dependent on their controlled interactions with biomolecules. Therefore, nanoparticles have often been surface-functionalized with a variety of ligands, not only to impart site specificity and increase cell penetration, but also to provide stealth properties and improve payload capacity. For example, the surface functionalization of nanoparticles has made remarkable advances in tumor-targeted delivery and drug delivery across the blood-brain barrier. This Special Issue will focus on recent progress in nanotechnology in the areas of basic and applied research, as well as clinical medicine. Topics of interest include, but are not limited to, cutting-edge research on the preparation of surface-functionalized nanoparticles and their in vitro and in vivo evaluation. Further, the interaction between nanoparticles and bio-interfaces will also be included.

Prof. Dr. Jagdish Singh
Dr. Buddhadev Layek
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 papers will be 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • drug delivery
  • gene delivery
  • nanoparticles
  • targeted drug delivery
  • surface-functionalized nanoparticles
  • pharmacokinetics
  • controlled release

Published Papers (7 papers)

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Research

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Open AccessCommunication
The Intercalation of CORM-2 with Pharmaceutical Clay Montmorillonite (MMT) Aids for Therapeutic Carbon Monoxide Release
Int. J. Mol. Sci. 2019, 20(14), 3453; https://doi.org/10.3390/ijms20143453 - 14 Jul 2019
Abstract
The pharmaceutical clay montmorillonite (MMT) is, for the first time, explored as a carbon monoxide-releasing material (CORMat). MMT consists of silicate double layered structure; its exfoliation feature intercalate the CORM-2 [RuCl(μ-Cl)(CO)3]2 inside the layers to suppress the toxicity of organometallic [...] Read more.
The pharmaceutical clay montmorillonite (MMT) is, for the first time, explored as a carbon monoxide-releasing material (CORMat). MMT consists of silicate double layered structure; its exfoliation feature intercalate the CORM-2 [RuCl(μ-Cl)(CO)3]2 inside the layers to suppress the toxicity of organometallic segment. The infrared spectroscopy (IR) confirmed the existence of ruthenium coordinated carbonyl ligand in MMT layers. The energy-dispersive X-ray spectroscopy (EDX) analysis showed that ruthenium element in this material was about 5%. The scanning electron microscopy (SEM) and transmission electron microscope (TEM) images showed that the layer-structure of MMT has been maintained after loading the ruthenium carbonyl segment. Moreover, the layers have been stretched out, which was confirmed by X-ray diffraction (XRD) analysis. Thermogravimetric (TG) curves with huge weight loss around 100–200 °C were attributed to the CO hot-release of ruthenium carbonyl as well as the loss of the adsorbed solvent molecules and the water molecules between the layers. The CO-liberating properties have been assessed through myoglobin assay. The horse myoglobin test showed that the material could be hydrolyzed to slowly release carbon monoxide in physiological environments. The half-life of CO release was much longer than that of CORM-3, and it has an excellent environmental tolerance and slow release effect. Full article
(This article belongs to the Special Issue Surface-Functionalized Nanoparticles as Drug Carriers)
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Open AccessArticle
Preparation and In Vitro/In Vivo Characterization of Polymeric Nanoparticles Containing Methotrexate to Improve Lymphatic Delivery
Int. J. Mol. Sci. 2019, 20(13), 3312; https://doi.org/10.3390/ijms20133312 - 05 Jul 2019
Abstract
Methotrexate (MTX) is a folic acid antagonist used as an effective drug to treat various kinds of cancers. However, MTX has limited use in cancer chemotherapy due to its adverse effects such as poor bioavailability, low specificity, drug resistance, and dose-dependent side effects. [...] Read more.
Methotrexate (MTX) is a folic acid antagonist used as an effective drug to treat various kinds of cancers. However, MTX has limited use in cancer chemotherapy due to its adverse effects such as poor bioavailability, low specificity, drug resistance, and dose-dependent side effects. To improve lymphatic delivery and reduce toxicity of MTX, MTX-loaded nanoparticles (NPs) were prepared in the present study. NPs were prepared with double emulsion solvent evaporation method using poly(lactide-co-glycolide) (PLGA). NPs were assessed for size, encapsulation efficiency, morphology, Fourier-transform infrared spectroscopy, X-ray diffraction, and thermal characterization. In vitro release profiles and cytotoxicity of these NPs were also evaluated. Prepared NPs and free MTX were administered orally or intravenously (5 mg/kg as MTX) to rats to evaluate their pharmacokinetic characteristics and lymphatic delivery effects. Mean particle size and encapsulation efficiency of NPs were 163.7 ± 10.25 nm and 93.3 ± 0.5%, respectively. Prepared NPs showed a sustained release profile of MTX in vitro and may be effective to cancer cells. Area under the blood concentration-time curve, total clearance, half-life, and lymphatic targeting efficiency were significantly different (p < 0.05) between prepared NPs and free MTX. These results demonstrate that MTX-loaded PLGA NPs are good candidates for targeted delivery of MTX to the lymphatic system. Full article
(This article belongs to the Special Issue Surface-Functionalized Nanoparticles as Drug Carriers)
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Open AccessArticle
Self-Assembled Benznidazole-Loaded Cationic Nanoparticles Containing Cholesterol/Sialic Acid: Physicochemical Properties, In Vitro Drug Release and In Vitro Anticancer Efficacy
Int. J. Mol. Sci. 2019, 20(9), 2350; https://doi.org/10.3390/ijms20092350 - 11 May 2019
Cited by 1
Abstract
Cationic polymeric nanoparticles (NPs) have the ability to overcome biological membranes, leading to improved efficacy of anticancer drugs. The modulation of the particle-cell interaction is desired to control this effect and avoid toxicity to normal cells. In this study, we explored the surface [...] Read more.
Cationic polymeric nanoparticles (NPs) have the ability to overcome biological membranes, leading to improved efficacy of anticancer drugs. The modulation of the particle-cell interaction is desired to control this effect and avoid toxicity to normal cells. In this study, we explored the surface functionalization of cationic polymethylmethacrylate (PMMA) NPs with two natural compounds, sialic acid (SA) and cholesterol (Chol). The performance of benznidazole (BNZ) was assessed in vitro in the normal renal cell line (HEK-293) and three human cancer cell lines, as follows: human colorectal cancer (HT-29), human cervical carcinoma (HeLa), and human hepatocyte carcinoma (HepG2). The structural properties and feasibility of NPs were evaluated and the changes induced by SA and Chol were determined by using multiple analytical approaches. Small (<200 nm) spherical NPs, with a narrow size distribution and high drug-loading efficiency were prepared by using a simple and reproducible emulsification solvent evaporation method. The drug interactions in the different self-assembled NPs were assessed by using Fourier transform-infrared spectroscopy. All formulations exhibited a slow drug-release profile and physical stability for more than 6 weeks. Both SA and Chol changed the kinetic properties of NPs and the anticancer efficacy. The feasibility and potential of SA/Chol-functionalized NPs has been demonstrated in vitro in the HEK-293, HepG2, HeLa, and HT-29 cell lines as a promising system for the delivery of BNZ. Full article
(This article belongs to the Special Issue Surface-Functionalized Nanoparticles as Drug Carriers)
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Open AccessArticle
Levan-Capped Silver Nanoparticles for Bactericidal Formulations: Release and Activity Modelling
Int. J. Mol. Sci. 2019, 20(6), 1502; https://doi.org/10.3390/ijms20061502 - 26 Mar 2019
Abstract
An environmentally friendly technique was used to produce levan-capped silver nanoparticles of about 30 nm (with a loading of 30%) that showed bactericide effect, for E. coli and B. subtilis. That effect was mathematically studied with a dose-response model (lethal dose of [...] Read more.
An environmentally friendly technique was used to produce levan-capped silver nanoparticles of about 30 nm (with a loading of 30%) that showed bactericide effect, for E. coli and B. subtilis. That effect was mathematically studied with a dose-response model (lethal dose of 12.4 ppm and 6.8 ppm respectively). These silver nanoparticles were subsequently introduced in a gel to create a silver release system with bacteria inhibition activity. Silver release from the gel and its bactericidal activity was theoretically studied to develop a unique model that is able to predict accurately both silver release and lethal dose for any type of bacteria. This model will be useful for performing predictions for future silver in gel applications. Full article
(This article belongs to the Special Issue Surface-Functionalized Nanoparticles as Drug Carriers)
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Open AccessArticle
Energy-Dependent Endocytosis Is Involved in the Absorption of Indomethacin Nanoparticles in the Small Intestine
Int. J. Mol. Sci. 2019, 20(3), 476; https://doi.org/10.3390/ijms20030476 - 22 Jan 2019
Cited by 1
Abstract
We previously reported that oral formulations containing indomethacin nanoparticles (IND-NPs) showed high bioavailability, and, consequently, improved therapeutic effects and reduced injury to the small intestine. However, the pathway for the transintestinal penetration of nanoparticles remained unclear. Thus, in this study, we investigated whether [...] Read more.
We previously reported that oral formulations containing indomethacin nanoparticles (IND-NPs) showed high bioavailability, and, consequently, improved therapeutic effects and reduced injury to the small intestine. However, the pathway for the transintestinal penetration of nanoparticles remained unclear. Thus, in this study, we investigated whether endocytosis was related to the penetration of IND-NPs (72.1 nm) using a transcell set with Caco-2 cells or rat intestine. Four inhibitors of various endocytosis pathways were used [nystatin, caveolae-dependent endocytosis (CavME); dynasore, clathrin-dependent endocytosis (CME); rottlerin, macropinocytosis; and cytochalasin D, phagocytosis inhibitor], and all energy-dependent endocytosis was inhibited at temperatures under 4 °C in this study. Although IND-NPs showed high transintestinal penetration, no particles were detected in the basolateral side. IND-NPs penetration was strongly prevented at temperatures under 4 °C. In experiments using pharmacological inhibitors, only CME inhibited penetration in the jejunum, while in the ileum, both CavME and CME significantly attenuated penetration. In conclusion, we found a novel pathway for the transintestinal penetration of drug nanoparticles. Our hypothesis was that nanoparticles would be taken up into the intestinal epithelium by endocytosis (CME in jejunum, CavME and CME in ileum), and dissolved and diffused in the intestine. Our findings are likely to be of significant use for the development of nanomedicines. Full article
(This article belongs to the Special Issue Surface-Functionalized Nanoparticles as Drug Carriers)
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Review

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Open AccessReview
Surface-Functionalized Nanoparticles as Efficient Tools in Targeted Therapy of Pregnancy Complications
Int. J. Mol. Sci. 2019, 20(15), 3642; https://doi.org/10.3390/ijms20153642 - 25 Jul 2019
Abstract
Minimizing exposure of the fetus to medication and reducing adverse off-target effects in the mother are the primary challenges in developing novel drugs to treat pregnancy complications. Nanomedicine has introduced opportunities for the development of novel platforms enabling targeted delivery of drugs in [...] Read more.
Minimizing exposure of the fetus to medication and reducing adverse off-target effects in the mother are the primary challenges in developing novel drugs to treat pregnancy complications. Nanomedicine has introduced opportunities for the development of novel platforms enabling targeted delivery of drugs in pregnancy. This review sets out to discuss the advances and potential of surface-functionalized nanoparticles in the targeted therapy of pregnancy complications. We first describe the human placental anatomy, which is fundamental for developing placenta-targeted therapy, and then we review current knowledge of nanoparticle transplacental transport mechanisms. Meanwhile, recent surface-functionalized nanoparticles for targeting the uterus and placenta are examined. Indeed, surface-functionalized nanoparticles could help prevent transplacental passage and promote placental-specific drug delivery, thereby enhancing efficacy and improving safety. We have achieved promising results in targeting the placenta via placental chondroitin sulfate A (plCSA), which is exclusively expressed in the placenta, using plCSA binding peptide (plCSA-BP)-decorated nanoparticles. Others have also focused on using placenta- and uterus-enriched molecules as targets to deliver therapeutics via surface-functionalized nanoparticles. Additionally, we propose that placenta-specific exosomes and surface-modified exosomes might be potential tools in the targeted therapy of pregnancy complications. Altogether, surface-functionalized nanoparticles have great potential value as clinical tools in the targeted therapy of pregnancy complications. Full article
(This article belongs to the Special Issue Surface-Functionalized Nanoparticles as Drug Carriers)
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Advances in Therapeutic Implications of Inorganic Drug Delivery Nano-Platforms for Cancer
Int. J. Mol. Sci. 2019, 20(4), 965; https://doi.org/10.3390/ijms20040965 - 22 Feb 2019
Cited by 5
Abstract
Numerous nanoparticles drug delivery systems for therapeutic implications in cancer treatment are in preclinical development as conventional chemotherapy has several drawbacks. A chemotherapeutic approach requires high doses of chemotherapeutic agents with low bioavailability, non-specific targeting, and above all, development of multiple drug resistance. [...] Read more.
Numerous nanoparticles drug delivery systems for therapeutic implications in cancer treatment are in preclinical development as conventional chemotherapy has several drawbacks. A chemotherapeutic approach requires high doses of chemotherapeutic agents with low bioavailability, non-specific targeting, and above all, development of multiple drug resistance. In recent years, inorganic nano-drug delivery platforms (NDDPs; with a metal core) have emerged as potential chemotherapeutic systems in oncology. One of the major goals of developing inorganic NDDPs is to effectively address the targeted anti-cancer drug(s) delivery related problems by carrying the therapeutic agents to desired tumors sites. In this current review, we delve into summarizing the recent developments in targeted release of anti-cancer drugs loaded in inorganic NDDPs such as mesoporous silica nanoparticles, carbon nanotubes, layered double hydroxides, superparamagnetic iron oxide nanoparticles and calcium phosphate nanoparticles together with highlighting their therapeutic performance at tumor sites. Full article
(This article belongs to the Special Issue Surface-Functionalized Nanoparticles as Drug Carriers)
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