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Nanoparticles Assisted Drug Delivery

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A special issue of Nanomaterials (ISSN 2079-4991).

Deadline for manuscript submissions: closed (15 October 2015) | Viewed by 117628

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Prof. Dr. Andrea Danani

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Department of Innovative Technologies, University of Applied Sciences and Arts of Southern Switzerland, Galleria 2, CH-6928 Manno, Switzerland
Interests: nanoparticles; drug delivery systems; computational modeling; virtual screening

Special Issue Information

Dear Colleagues,

Delivering therapeutic compounds to the target site is a major problem in the treatment of many diseases. Nanocarriers as drug delivery systems (DDSs) are designed to improve the efficacy and to reduce the toxicity of drugs by providing control of biodistribution and pharmacokinetics. Moreover, the combination of active molecules with nanocarriers can protect them against both inactivation and degradation. In comparison with traditional unconjugated drugs, nanocarrier-drug complexes are more effective and selective. As a consequence, the required doses of drugs are lower offering various advantages.

However, despite the large expectations with regards to nanoparticle DDS (nDDSs), they still have several drawbacks and limitations that need to be tackled. For instance, nanocarrier-drug complexes can be phagocytosed by unspecific cells, especially immune cells, giving rise to safety concerns. Moreover, the small size and large surface area can lead to an aggregation, leading to scaling up problems, and making their handling difficult.

Despite all these limitations, nDDSs have a great potential to solve many of the current open issues in drug-treatment. However, to provide a clinically successful DDSs-portfolio, for example, the following challenges have to be overcome: improving biocompatibility, drug loading customization, interaction with biological barriers controlling, immune-defense escape, targeting and release optimization, experimental protocols standardization, and monitoring the exposure level assessing the impact on the environment.

For this Special Issue, we are especially interested in manuscripts that deal with the major classes of nanoparticle platforms: liposomes, polymers, dendrimers, lipid-polymer hybrids, silica, and magnetic nanoparticles. They have to address the aforementioned examples of challenges, with a particular emphasis on their applications in the targeted and controlled delivery of therapeutic molecules, as well as in biocompatibility. This Special Issue invites both experimental and computational-based manuscripts.

Prof. Dr. Andrea Danani
Guest Editor

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Keywords

drug delivery system
nanoparticles
nanocarriers
nanotoxicity
targeting therapy
toxicology

Published Papers (11 papers)

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Research

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2611 KiB

Open AccessArticle

Repair of the Orbital Wall Fractures in Rabbit Animal Model Using Nanostructured Hydroxyapatite-Based Implant

by Sinziana Gradinaru, Laura Madalina Popescu, Roxana Mioara Piticescu, Sabina Zurac, Radu Ciuluvica, Alexandrina Burlacu, Raluca Tutuianu, Sorina-Nicoleta Valsan, Adrian Mihail Motoc and Liliana Mary Voinea

Nanomaterials 2016, 6(1), 11; https://0-doi-org.brum.beds.ac.uk/10.3390/nano6010011 - 07 Jan 2016

Cited by 9 | Viewed by 5788

Abstract

Cellular uptake and cytotoxicity of nanostructured hydroxyapatite (nanoHAp) are dependent on its physical parameters. Therefore, an understanding of both surface chemistry and morphology of nanoHAp is needed in order to be able to anticipate its in vivo behavior. The aim of this paper is to characterize an engineered nanoHAp in terms of physico-chemical properties, biocompatibility, and its capability to reconstitute the orbital wall fractures in rabbits. NanoHAp was synthesized using a high pressure hydrothermal method and characterized by physico-chemical, structural, morphological, and optical techniques. X-ray diffraction revealed HAp crystallites of 21 nm, while Scanning Electron Microscopy (SEM) images showed spherical shapes of HAp powder. Mean particle size of HAp measured by DLS technique was 146.3 nm. Biocompatibility was estimated by the effect of HAp powder on the adhesion and proliferation of mesenchymal stem cells (MSC) in culture. The results showed that cell proliferation on powder-coated slides was between 73.4% and 98.3% of control cells (cells grown in normal culture conditions). Computed tomography analysis of the preformed nanoHAp implanted in orbital wall fractures, performed at one and two months postoperative, demonstrated the integration of the implants in the bones. In conclusion, our engineered nanoHAp is stable, biocompatible, and may be safely considered for reconstruction of orbital wall fractures. Full article

(This article belongs to the Special Issue Nanoparticles Assisted Drug Delivery)

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4645 KiB

Open AccessFeature PaperArticle

Targeted Sterically Stabilized Phospholipid siRNA Nanomedicine for Hepatic and Renal Fibrosis

by Fatima Khaja, Dulari Jayawardena, Antonina Kuzmis and Hayat Önyüksel

Nanomaterials 2016, 6(1), 8; https://0-doi-org.brum.beds.ac.uk/10.3390/nano6010008 - 05 Jan 2016

Cited by 20 | Viewed by 6282

Abstract

Since its discovery, small interfering RNA (siRNA) has been considered a potent tool for modulating gene expression. It has the ability to specifically target proteins via selective degradation of messenger RNA (mRNA) not easily accessed by conventional drugs. Hence, RNA interference (RNAi) therapeutics have great potential in the treatment of many diseases caused by faulty protein expression such as fibrosis and cancer. However, for clinical application siRNA faces a number of obstacles, such as poor in vivo stability, and off-target effects. Here we developed a unique targeted nanomedicine to tackle current siRNA delivery issues by formulating a biocompatible, biodegradable and relatively inexpensive nanocarrier of sterically stabilized phospholipid nanoparticles (SSLNPs). This nanocarrier is capable of incorporating siRNA in its core through self-association with a novel cationic lipid composed of naturally occuring phospholipids and amino acids. This overall assembly protects and delivers sufficient amounts of siRNA to knockdown over-expressed protein in target cells. The siRNA used in this study, targets connective tissue growth factor (CTGF), an important regulator of fibrosis in both hepatic and renal cells. Furthermore, asialoglycoprotein receptors are targeted by attaching the galactosamine ligand to the nanocarries which enhances the uptake of nanoparticles by hepatocytes and renal tubular epithelial cells, the major producers of CTGF in fibrosis. On animals this innovative nanoconstruct, small interfering RNA in sterically stabilized phospholipid nanoparticles (siRNA-SSLNP), showed favorable pharmacokinetic properties and accumulated mostly in hepatic and renal tissues making siRNA-SSLNP a suitable system for targeting liver and kidney fibrotic diseases. Full article

(This article belongs to the Special Issue Nanoparticles Assisted Drug Delivery)

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4545 KiB

Open AccessArticle

Effects of Particle Hydrophobicity, Surface Charge, Media pH Value and Complexation with Human Serum Albumin on Drug Release Behavior of Mitoxantrone-Loaded Pullulan Nanoparticles

by Xiaojun Tao, Shu Jin, Dehong Wu, Kai Ling, Liming Yuan, Pingfa Lin, Yongchao Xie and Xiaoping Yang

Nanomaterials 2016, 6(1), 2; https://0-doi-org.brum.beds.ac.uk/10.3390/nano6010002 - 25 Dec 2015

Cited by 34 | Viewed by 7588

Abstract

We prepared two types of cholesterol hydrophobically modified pullulan nanoparticles (CHP) and carboxyethyl hydrophobically modified pullulan nanoparticles (CHCP) substituted with various degrees of cholesterol, including 3.11, 6.03, 6.91 and 3.46 per polymer, and named CHP_−3.11, CHP_−6.03, CHP_−6.91 and CHCP_−3.46. Dynamic laser light scattering (DLS) showed that the pullulan nanoparticles were 80–120 nm depending on the degree of cholesterol substitution. The mean size of CHCP nanoparticles was about 160 nm, with zeta potential −19.9 mV, larger than CHP because of the carboxyethyl group. A greater degree of cholesterol substitution conferred greater nanoparticle hydrophobicity. Drug-loading efficiency depended on nanoparticle hydrophobicity, that is, nanoparticles with the greatest degree of cholesterol substitution (6.91) showed the most drug encapsulation efficiency (90.2%). The amount of drug loading increased and that of drug release decreased with enhanced nanoparticle hydrophobicity. Nanoparticle surface-negative charge disturbed the amount of drug loading and drug release, for an opposite effect relative to nanoparticle hydrophobicity. The drug release in pullulan nanoparticles was higher pH 4.0 than pH 6.8 media. However, the changed drug release amount was not larger for negative-surface nanoparticles than CHP nanoparticles in the acid release media. Drug release of pullulan nanoparticles was further slowed with human serum albumin complexation and was little affected by nanoparticle hydrophobicity and surface negative charge. Full article

(This article belongs to the Special Issue Nanoparticles Assisted Drug Delivery)

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2255 KiB

Open AccessArticle

Non-Cytotoxic Quantum Dot–Chitosan Nanogel Biosensing Probe for Potential Cancer Targeting Agent

by Tyler Maxwell, Tahmina Banu, Edward Price, Jeremy Tharkur, Maria Gabriela Nogueira Campos, Andre Gesquiere and Swadeshmukul Santra

Nanomaterials 2015, 5(4), 2359-2379; https://0-doi-org.brum.beds.ac.uk/10.3390/nano5042359 - 18 Dec 2015

Cited by 18 | Viewed by 7102

Abstract

Quantum dot (Qdot) biosensors have consistently provided valuable information to researchers about cellular activity due to their unique fluorescent properties. Many of the most popularly used Qdots contain cadmium, posing the risk of toxicity that could negate their attractive optical properties. The design of a non-cytotoxic probe usually involves multiple components and a complex synthesis process. In this paper, the design and synthesis of a non-cytotoxic Qdot-chitosan nanogel composite using straight-forward cyanogen bromide (CNBr) coupling is reported. The probe was characterized by spectroscopy (UV-Vis, fluorescence), microscopy (Fluorescence, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Dynamic Light Scattering. This activatable (“OFF”/“ON”) probe contains a core–shell Qdot (CdS:Mn/ZnS) capped with dopamine, which acts as a fluorescence quencher and a model drug. Dopamine capped “OFF” Qdots can undergo ligand exchange with intercellular glutathione, which turns the Qdots “ON” to restore fluorescence. These Qdots were then coated with chitosan (natural biocompatible polymer) functionalized with folic acid (targeting motif) and Fluorescein Isothiocyanate (FITC; fluorescent dye). To demonstrate cancer cell targetability, the interaction of the probe with cells that express different folate receptor levels was analyzed, and the cytotoxicity of the probe was evaluated on these cells and was shown to be nontoxic even at concentrations as high as 100 mg/L. Full article

(This article belongs to the Special Issue Nanoparticles Assisted Drug Delivery)

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788 KiB

Open AccessArticle

Nanocarriers for DNA Vaccines: Co-Delivery of TLR-9 and NLR-2 Ligands Leads to Synergistic Enhancement of Proinflammatory Cytokine Release

by Johanna Poecheim, Simon Heuking, Livia Brunner, Christophe Barnier-Quer, Nicolas Collin and Gerrit Borchard

Nanomaterials 2015, 5(4), 2317-2334; https://0-doi-org.brum.beds.ac.uk/10.3390/nano5042317 - 17 Dec 2015

Cited by 11 | Viewed by 6212

Abstract

Adjuvants enhance immunogenicity of vaccines through either targeted antigen delivery or stimulation of immune receptors. Three cationic nanoparticle formulations were evaluated for their potential as carriers for a DNA vaccine, and muramyl dipeptide (MDP) as immunostimulatory agent, to induce and increase immunogenicity of Mycobacterium tuberculosis antigen encoding plasmid DNA (pDNA). The formulations included (1) trimethyl chitosan (TMC) nanoparticles, (2) a squalene-in-water nanoemulsion, and (3) a mineral oil-in-water nanoemulsion. The adjuvant effect of the pDNA-nanocomplexes was evaluated by serum antibody analysis in immunized mice. All three carriers display a strong adjuvant effect, however, only TMC nanoparticles were capable to bias immune responses towards Th1. pDNA naturally contains immunostimulatory unmethylated CpG motifs that are recognized by Toll-like receptor 9 (TLR-9). In mechanistic in vitro studies, activation of TLR-9 and the ability to enhance immunogenicity by simultaneously targeting TLR-9 and NOD-like receptor 2 (NLR-2) was determined by proinflammatory cytokine release in RAW264.7 macrophages. pDNA in combination with MDP was shown to significantly increase proinflammatory cytokine release in a synergistic manner, dependent on NLR-2 activation. In summary, novel pDNA-Ag85A loaded nanoparticle formulations, which induce antigen specific immune responses in mice were developed, taking advantage of the synergistic combinations of TLR and NLR agonists to increase the adjuvanticity of the carriers used. Full article

(This article belongs to the Special Issue Nanoparticles Assisted Drug Delivery)

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751 KiB

Open AccessArticle

Cytotoxicity, Uptake Behaviors, and Oral Absorption of Food Grade Calcium Carbonate Nanomaterials

by Mi-Kyung Kim, Jeong-A. Lee, Mi-Rae Jo, Min-Kyu Kim, Hyoung-Mi Kim, Jae-Min Oh, Nam Woong Song and Soo-Jin Choi

Nanomaterials 2015, 5(4), 1938-1954; https://0-doi-org.brum.beds.ac.uk/10.3390/nano5041938 - 10 Nov 2015

Cited by 38 | Viewed by 7338

Abstract

Calcium is the most abundant mineral in human body and essential for the formation and maintenance of bones and teeth as well as diverse cellular functions. Calcium carbonate (CaCO₃) is widely used as a dietary supplement; however, oral absorption efficiency of CaCO₃ is extremely low, which may be overcome by applying nano-sized materials. In this study, we evaluated the efficacy of food grade nano CaCO₃ in comparison with that of bulk- or reagent grade nano CaCO₃ in terms of cytotoxicity, cellular uptake, intestinal transport, and oral absorption. Cytotoxicity results demonstrated that nano-sized CaCO₃ particles were slightly more toxic than bulk materials in terms of oxidative stress and membrane damage. Cellular uptake behaviors of CaCO₃ nanoparticles were different from bulk CaCO₃ or Ca²⁺ ions in human intestinal epithelial cells, showing efficient cellular internalization and elevated intracellular Ca²⁺ levels. Meanwhile, CaCO₃ nanoparticles were efficiently transported by microfold (M) cells in vitro model of human intestinal follicle-associated epithelium, in a similar manner as Ca²⁺ ions did. Biokinetic study revealed that the biological fate of CaCO₃ particles was different from Ca²⁺ ions; however, in vivo, its oral absorption was not significantly affected by particle size. These findings provide crucial information to understand and predict potential toxicity and oral absorption efficiency of food grade nanoparticles. Full article

(This article belongs to the Special Issue Nanoparticles Assisted Drug Delivery)

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2829 KiB

Open AccessArticle

Dendrimer-Functionalized Laponite Nanodisks as a Platform for Anticancer Drug Delivery

by Rania Mustafa, Yu Luo, Yilun Wu, Rui Guo and Xiangyang Shi

Nanomaterials 2015, 5(4), 1716-1731; https://0-doi-org.brum.beds.ac.uk/10.3390/nano5041716 - 20 Oct 2015

Cited by 25 | Viewed by 6571

Abstract

In this study, we synthesized dendrimer-functionalized laponite (LAP) nanodisks for loading and delivery of anticancer drug doxorubicin (DOX). Firstly, LAP was modified with silane coupling agents and succinic anhydride to render abundant carboxyl groups on the surface of LAP. Then, poly(amidoamine) (PAMAM) dendrimer of generation 2 (G2) were conjugated to form LM-G2 nanodisks. Anticancer drug DOX was then loaded on the LM-G2 with an impressively high drug loading efficiency of 98.4% and could be released in a pH-sensitive and sustained manner. Moreover, cell viability assay results indicate that LM-G2/DOX complexes could more effectively inhibit the proliferation of KB cells (a human epithelial carcinoma cell line) than free DOX at the same drug concentration. Flow cytometry analysis and confocal laser scanning microscope demonstrated that LM-G2/DOX could be uptaken by KB cells more effectively than free DOX. Considering the exceptional high drug loading efficiency and the abundant dendrimer amine groups on the surface that can be further modified, the developed LM-G2 nanodisks may hold a great promise to be used as a novel platform for anticancer drug delivery. Full article

(This article belongs to the Special Issue Nanoparticles Assisted Drug Delivery)

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Review

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2340 KiB

Open AccessReview

Manufacturing Techniques and Surface Engineering of Polymer Based Nanoparticles for Targeted Drug Delivery to Cancer

by Yichao Wang, Puwang Li, Thao Truong-Dinh Tran, Juan Zhang and Lingxue Kong

Nanomaterials 2016, 6(2), 26; https://0-doi-org.brum.beds.ac.uk/10.3390/nano6020026 - 01 Feb 2016

Cited by 167 | Viewed by 17639

Abstract

The evolution of polymer based nanoparticles as a drug delivery carrier via pharmaceutical nano/microencapsulation has greatly promoted the development of nano- and micro-medicine in the past few decades. Poly(lactide-co-glycolide) (PLGA) and chitosan, which are biodegradable and biocompatible polymers, have been approved by both the Food & Drug Administration (FDA) and European Medicine Agency (EMA), making them ideal biomaterials that can be advanced from laboratory development to clinical oral and parental administrations. PLGA and chitosan encapsulated nanoparticles (NPs) have successfully been developed as new oral drug delivery systems with demonstrated high efficacy. This review aims to provide a comprehensive overview of the fabrication of PLGA and chitosan particulate systems using nano/microencapsulation methods, the current progress and the future outlooks of the nanoparticulate drug delivery systems. Especially, we focus on the formulations and nano/micro-encapsulation techniques using top-down techniques. It also addresses how the different phases including the organic and aqueous ones in the emulsion system interact with each other and subsequently influence the properties of the drug delivery system. Besides, surface modification strategies which can effectively engineer intrinsic physicochemical properties are summarised. Finally, future perspectives and potential directions of PLGA and chitosan nano/microencapsulated drug systems are outlined. Full article

(This article belongs to the Special Issue Nanoparticles Assisted Drug Delivery)

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2269 KiB

Open AccessReview

Excipient Nanoemulsions for Improving Oral Bioavailability of Bioactives

by Laura Salvia-Trujillo, Olga Martín-Belloso and David Julian McClements

Nanomaterials 2016, 6(1), 17; https://0-doi-org.brum.beds.ac.uk/10.3390/nano6010017 - 14 Jan 2016

Cited by 90 | Viewed by 12133

Abstract

The oral bioavailability of many hydrophobic bioactive compounds found in natural food products (such as vitamins and nutraceuticals in fruits and vegetables) is relatively low due to their low bioaccessibility, chemical instability, or poor absorption. Most previous research has therefore focused on the design of delivery systems to incorporate isolated bioactive compounds into food products. However, a more sustainable and cost-effect approach to enhancing the functionality of bioactive compounds is to leave them within their natural environment, but specifically design excipient foods that enhance their bioavailability. Excipient foods typically do not have functionality themselves but they have the capacity to enhance the functionality of nutrients present in natural foods by altering their bioaccessibility, absorption, and/or chemical transformation. In this review article we present the use of excipient nanoemulsions for increasing the bioavailability of bioactive components from fruits and vegetables. Nanoemulsions present several advantages over other food systems for this application, such as the ability to incorporate hydrophilic, amphiphilic, and lipophilic excipient ingredients, high physical stability, and rapid gastrointestinal digestibility. The design, fabrication, and application of nanoemulsions as excipient foods will therefore be described in this article. Full article

(This article belongs to the Special Issue Nanoparticles Assisted Drug Delivery)

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6363 KiB

Open AccessFeature PaperReview

Composites of Polymer Hydrogels and Nanoparticulate Systems for Biomedical and Pharmaceutical Applications

by Fuli Zhao, Dan Yao, Ruiwei Guo, Liandong Deng, Anjie Dong and Jianhua Zhang

Nanomaterials 2015, 5(4), 2054-2130; https://0-doi-org.brum.beds.ac.uk/10.3390/nano5042054 - 03 Dec 2015

Cited by 285 | Viewed by 25044

Abstract

Due to their unique structures and properties, three-dimensional hydrogels and nanostructured particles have been widely studied and shown a very high potential for medical, therapeutic and diagnostic applications. However, hydrogels and nanoparticulate systems have respective disadvantages that limit their widespread applications. Recently, the incorporation of nanostructured fillers into hydrogels has been developed as an innovative means for the creation of novel materials with diverse functionality in order to meet new challenges. In this review, the fundamentals of hydrogels and nanoparticles (NPs) were briefly discussed, and then we comprehensively summarized recent advances in the design, synthesis, functionalization and application of nanocomposite hydrogels with enhanced mechanical, biological and physicochemical properties. Moreover, the current challenges and future opportunities for the use of these promising materials in the biomedical sector, especially the nanocomposite hydrogels produced from hydrogels and polymeric NPs, are discussed. Full article

(This article belongs to the Special Issue Nanoparticles Assisted Drug Delivery)

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730 KiB

Open AccessReview

Multifunctional Nanomaterials and Their Applications in Drug Delivery and Cancer Therapy

by Mathangi Srinivasan, Mehdi Rajabi and Shaker A. Mousa

Nanomaterials 2015, 5(4), 1690-1703; https://0-doi-org.brum.beds.ac.uk/10.3390/nano5041690 - 14 Oct 2015

Cited by 111 | Viewed by 14703

Abstract

The field of nanotechnology has led to the development of many innovative strategies for effective detection and treatment of cancer, overcoming limitations associated with conventional cancer diagnosis and therapy. Multifunctional nanoparticle systems can integrate imaging, targeting and treatment moieties on the surface and in the core, resulting in targeted delivery of the imaging or treatment modalities, specifically to the tumor. Multifunctional nanoparticles also enable simultaneous delivery of multiple treatment agents, resulting in effective combinatorial therapeutic regimens against cancer. In this review, various multifunctional nanoparticle systems that feature a variety of targeting moieties for in vitro and/or in vivo cancer imaging and therapy are discussed. Full article

(This article belongs to the Special Issue Nanoparticles Assisted Drug Delivery)

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