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Surface-Functionalized Nanoparticles as Drug Carriers

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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) | Viewed by 57315

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Prof. Dr. Jagdish Singh

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Guest Editor

Department of Pharmaceutical Sciences, College of Health Professions, North Dakota State University, Fargo, ND 58108-6050, USA
Interests: nanoparticle; targeted delivery; brain-drug delivery; intranasal; nanomicelles; liposomes
Special Issues, Collections and Topics in MDPI journals

Dr. Buddhadev Layek

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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, Collections and Topics 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

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Keywords

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

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Published Papers (10 papers)

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Editorial

Jump to: Research, Review

5 pages, 194 KiB

Open AccessEditorial

Editorial of Special Issue “Surface-Functionalized Nanoparticles as Drug Carriers”

by Buddhadev Layek and Jagdish Singh

Int. J. Mol. Sci. 2019, 20(24), 6352; https://doi.org/10.3390/ijms20246352 - 17 Dec 2019

Cited by 4 | Viewed by 2443

Abstract

Safe and effective delivery of therapeutics at the target site is the key to successful therapy. Nanocarriers can offer significant advantages over conventional dosage forms. Over the decades, nanoparticles have been extensively used to increase bioavailability, improve solubility and stability, reduce toxicities, and facilitate the controlled release of therapeutics. Further, nanoparticles have often been surface-functionalized with a variety of ligands to enhance circulation half-life and increase target-specificity. Although nanotechnology has shown significant therapeutic benefits for multiple biomedical applications, limited nanoparticle-based formulations have progressed to clinical trials, and only a few have reached the pharmaceutical market. This editorial is an introduction to the special issue entitled Surface-Functionalized Nanoparticles as Drug Carriers. We outline the scope of the special issue, summarize the results and conclusions of the nine articles published in this issue, and provide perspective on the application of surface-functionalized nanoparticles in the drug delivery field. Full article

(This article belongs to the Special Issue Surface-Functionalized Nanoparticles as Drug Carriers)

Research

Jump to: Editorial, Review

16 pages, 1879 KiB

Open AccessArticle

Quantification of Surface GalNAc Ligands Decorating Nanostructured Lipid Carriers by UPLC-ELSD

by Laura Gauthier, Mathieu Varache, Anne-Claude Couffin, Colette Lebrun, Pascale Delangle, Christelle Gateau and Isabelle Texier

Int. J. Mol. Sci. 2019, 20(22), 5669; https://doi.org/10.3390/ijms20225669 - 12 Nov 2019

Cited by 5 | Viewed by 3572

Abstract

Nanoparticles have been extensively studied for drug delivery and targeting to specific organs. The functionalization of the nanoparticle surface by site-specific ligands (antibodies, peptides, saccharides) can ensure efficient recognition and binding with relevant biological targets. One of the main challenges in the development of these decorated nanocarriers is the accurate quantification of the amount of ligands on the nanoparticle surface. In this study, nanostructured lipid carriers (NLC) were functionalized with N-acetyl-D-galactosamine (GalNAc) units, known to target the asialoglycoprotein receptor (ASGPR). Different molar percentages of GalNAc-functionalized surfactant (0%, 2%, 5%, and 14%) were used in the formulation. Based on ultra-high-performance liquid chromatography separation and evaporative light-scattering detection (UPLC-ELSD), an analytical method was developed to specifically quantify the amount of GalNAc units present at the NLC surface. This method allowed the accurate quantification of GalNAc surfactant and therefore gave some insights into the structural parameters of these multivalent ligand systems. Our data show that the GalNAc decorated NLC possess large numbers of ligands at their surface and suitable distances between them for efficient multivalent interaction with the ASGPR, and therefore promising liver-targeting efficiency. Full article

(This article belongs to the Special Issue Surface-Functionalized Nanoparticles as Drug Carriers)

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16 pages, 10822 KiB

Open AccessCommunication

The Intercalation of CORM-2 with Pharmaceutical Clay Montmorillonite (MMT) Aids for Therapeutic Carbon Monoxide Release

by Muhammad Faizan, Kifayat Ullah Khan Niazi, Niaz Muhammad, Yongxia Hu, Yanyan Wang, Dezhi Lin, Yuanyuan Liu, Weiqiang Zhang and Ziwei Gao

Int. J. Mol. Sci. 2019, 20(14), 3453; https://doi.org/10.3390/ijms20143453 - 14 Jul 2019

Cited by 7 | Viewed by 4019

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 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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24 pages, 5376 KiB

Open AccessArticle

Preparation and In Vitro/In Vivo Characterization of Polymeric Nanoparticles Containing Methotrexate to Improve Lymphatic Delivery

by Ji-Hun Jang, Seung-Hyun Jeong and Yong-Bok Lee

Int. J. Mol. Sci. 2019, 20(13), 3312; https://doi.org/10.3390/ijms20133312 - 5 Jul 2019

Cited by 58 | Viewed by 5405

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. 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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16 pages, 2355 KiB

Open AccessArticle

Self-Assembled Benznidazole-Loaded Cationic Nanoparticles Containing Cholesterol/Sialic Acid: Physicochemical Properties, In Vitro Drug Release and In Vitro Anticancer Efficacy

by Alaine Maria dos Santos-Silva, Lilia Basílio de Caland, Ednaldo Gomes do Nascimento, Ana Luiza C. de S.L. Oliveira, Raimundo F. de Araújo-Júnior, Alianda Maira Cornélio, Matheus F. Fernandes-Pedrosa and Arnóbio Antônio da Silva-Júnior

Int. J. Mol. Sci. 2019, 20(9), 2350; https://doi.org/10.3390/ijms20092350 - 11 May 2019

Cited by 16 | Viewed by 3640

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 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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19 pages, 5163 KiB

Open AccessArticle

Levan-Capped Silver Nanoparticles for Bactericidal Formulations: Release and Activity Modelling

by Álvaro González-Garcinuño, Rubén Masa, María Hernández, Ángel Domínguez, Antonio Tabernero and Eva Martín del Valle

Int. J. Mol. Sci. 2019, 20(6), 1502; https://doi.org/10.3390/ijms20061502 - 26 Mar 2019

Cited by 24 | Viewed by 4784

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 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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14 pages, 3091 KiB

Open AccessArticle

Energy-Dependent Endocytosis Is Involved in the Absorption of Indomethacin Nanoparticles in the Small Intestine

by Miyu Ishii, Yuya Fukuoka, Saori Deguchi, Hiroko Otake, Tadatoshi Tanino and Noriaki Nagai

Int. J. Mol. Sci. 2019, 20(3), 476; https://doi.org/10.3390/ijms20030476 - 22 Jan 2019

Cited by 34 | Viewed by 7597

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 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

Jump to: Editorial, Research

25 pages, 3276 KiB

Open AccessReview

Overcoming Hurdles in Nanoparticle Clinical Translation: The Influence of Experimental Design and Surface Modification

by Jacob W. Shreffler, Jessica E. Pullan, Kaitlin M. Dailey, Sanku Mallik and Amanda E. Brooks

Int. J. Mol. Sci. 2019, 20(23), 6056; https://doi.org/10.3390/ijms20236056 - 30 Nov 2019

Cited by 95 | Viewed by 7615

Abstract

Nanoparticles are becoming an increasingly popular tool for biomedical imaging and drug delivery. While the prevalence of nanoparticle drug-delivery systems reported in the literature increases yearly, relatively little translation from the bench to the bedside has occurred. It is crucial for the scientific community to recognize this shortcoming and re-evaluate standard practices in the field, to increase clinical translatability. Currently, nanoparticle drug-delivery systems are designed to increase circulation, target disease states, enhance retention in diseased tissues, and provide targeted payload release. To manage these demands, the surface of the particle is often modified with a variety of chemical and biological moieties, including PEG, tumor targeting peptides, and environmentally responsive linkers. Regardless of the surface modifications, the nano–bio interface, which is mediated by opsonization and the protein corona, often remains problematic. While fabrication and assessment techniques for nanoparticles have seen continued advances, a thorough evaluation of the particle’s interaction with the immune system has lagged behind, seemingly taking a backseat to particle characterization. This review explores current limitations in the evaluation of surface-modified nanoparticle biocompatibility and in vivo model selection, suggesting a promising standardized pathway to clinical translation. Full article

(This article belongs to the Special Issue Surface-Functionalized Nanoparticles as Drug Carriers)

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16 pages, 1263 KiB

Open AccessReview

Surface-Functionalized Nanoparticles as Efficient Tools in Targeted Therapy of Pregnancy Complications

by Baozhen Zhang, Ruijing Liang, Mingbin Zheng, Lintao Cai and Xiujun Fan

Int. J. Mol. Sci. 2019, 20(15), 3642; https://doi.org/10.3390/ijms20153642 - 25 Jul 2019

Cited by 46 | Viewed by 9014

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 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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17 pages, 765 KiB

Open AccessReview

Advances in Therapeutic Implications of Inorganic Drug Delivery Nano-Platforms for Cancer

by Safia Naz, Muhammad Shamoon, Rui Wang, Li Zhang, Juan Zhou and Jinghua Chen

Int. J. Mol. Sci. 2019, 20(4), 965; https://doi.org/10.3390/ijms20040965 - 22 Feb 2019

Cited by 66 | Viewed by 8442

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. 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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