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Dendrimers in Medicine
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Dendrimers in Medicine

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (20 April 2018) | Viewed by 62761

Special Issue Editors

Dr. Mohammad Najlah

E-Mail Website
Guest Editor
School of Allied Health, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Bishop Hall Lane, Chelmsford CM1 1SQ, UK
Interests: dendrimer nanocarriers; biopolymers; clinical pharmaceutics; polymer nanoparticulates
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Antony D’Emanuele

E-Mail Website
Guest Editor
Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK
Interests: polymeric delivery systems (including dendrimer, biodegradable and hydrogel systems); nanomedicines; responsive drug delivery technologies; controlled drug delivery technologies; colloidal formulation

Special Issue Information

Dear Colleagues,

Dendrimers, having precise nanostructures with synthetic control over: size, shape, and surface chemistry, are currently receiving great attention in a wide range of pharmaceutical and biomedical applications such as gene transfection, drug solubilisation, immunoassay, magnetic resonance imaging, chelating agents, and drug delivery. These highly branched macromolecules—described as having a well-defined, homogeneous, and monodisperse nanostructure—have a typically symmetric core, an inner shell, and terminal functional groups. The unique chemistry of dendrimers offers great opportunities to be tailored/engineered to facilitate drug conjugation (prodrug), drug encapsulation and/or surface modification with designed moieties that exhibit desired properties such as targeting, long circulation, etc. This Special Issue will provide a platform for presenting the latest research results on dendrimer applications in medicine.

Dr. Mohammad Najlah
Prof. Antony D’Emanuele
Guest Editors

Manuscript Submission Information

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Keywords

  • Dendrimers
  • Drug delivery
  • Biodegradable
  • Targeting
  • Biocompatible
  • Functional groups
  • Solubility
  • Targeting
  • Bioavailability
  • Conjugation
  • Encapsulation

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Published Papers (7 papers)

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Research

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15 pages, 3287 KiB  
Article
Self-Assembly Behavior of Amphiphilic Janus Dendrimers in Water: A Combined Experimental and Coarse-Grained Molecular Dynamics Simulation Approach
by Mariana E. Elizondo-García, Valeria Márquez-Miranda, Ingrid Araya-Durán, Jesús A. Valencia-Gallegos and Fernando D. González-Nilo
Molecules 2018, 23(4), 969; https://doi.org/10.3390/molecules23040969 - 21 Apr 2018
Cited by 9 | Viewed by 7444
Abstract
Amphiphilic Janus dendrimers (JDs) are repetitively branched molecules with hydrophilic and hydrophobic components that self-assemble in water to form a variety of morphologies, including vesicles analogous to liposomes with potential pharmaceutical and medical application. To date, the self-assembly of JDs has not been [...] Read more.
Amphiphilic Janus dendrimers (JDs) are repetitively branched molecules with hydrophilic and hydrophobic components that self-assemble in water to form a variety of morphologies, including vesicles analogous to liposomes with potential pharmaceutical and medical application. To date, the self-assembly of JDs has not been fully investigated thus it is important to gain insight into its mechanism and dependence on JDs’ molecular structure. In this study, the aggregation behavior in water of a second-generation bis-MPA JD was evaluated using experimental and computational methods. Dispersions of JDs in water were carried out using the thin-film hydration and ethanol injection methods. Resulting assemblies were characterized by dynamic light scattering, confocal microscopy, and atomic force microscopy. Furthermore, a coarse-grained molecular dynamics (CG-MD) simulation was performed to study the mechanism of JDs aggregation. The obtaining of assemblies in water with no interdigitated bilayers was confirmed by the experimental characterization and CG-MD simulation. Assemblies with dendrimersome characteristics were obtained using the ethanol injection method. The results of this study establish a relationship between the molecular structure of the JD and the properties of its aggregates in water. Thus, our findings could be relevant for the design of novel JDs with tailored assemblies suitable for drug delivery systems. Full article
(This article belongs to the Special Issue Dendrimers in Medicine)
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12 pages, 3202 KiB  
Article
In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates
by Mohammad Najlah, Sally Freeman, Mouhamad Khoder, David Attwood and Antony D’Emanuele
Molecules 2017, 22(10), 1661; https://doi.org/10.3390/molecules22101661 - 4 Oct 2017
Cited by 24 | Viewed by 7264
Abstract
The present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM) dendrimers as drug carriers of naproxen (NAP), a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio [...] Read more.
The present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM) dendrimers as drug carriers of naproxen (NAP), a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio via a diethylene glycol linker. A lauroyl chain (L), a lipophilic permeability enhancer, was attached to G3 and G0 prodrugs. The G3 and G0 conjugates were more hydrophilic than naproxen as evaluated by the measurement of partitioning between 1-octanol and a phosphate buffer at pH 7.4 and pH 1.2. The unmodified surface PAMAM-NAP conjugates showed significant solubility enhancements of NAP at pH 1.2; however, with the number of NAP conjugated to G3, this was limited to 10 molecules. The lactate dehydrogenase (LDH) assay indicated that the G3 dendrimer conjugates had a concentration dependent toxicity towards Caco-2 cells. Attaching naproxen to the surface of the dendrimer increased the IC50 of the resulting prodrugs towards Caco-2 cells. The lauroyl G3 conjugates showed the highest toxicity amongst the PAMAM dendrimer conjugates investigated and were significantly more toxic than the lauroyl-G0-naproxen conjugates. The permeability of naproxen across monolayers of Caco-2 cells was significantly increased by its conjugation to either G3 or G0 PAMAM dendrimers. Lauroyl-G0 conjugates displayed considerably lower cytotoxicity than G3 conjugates and may be preferable for use as a drug carrier for low soluble drugs such as naproxen. Full article
(This article belongs to the Special Issue Dendrimers in Medicine)
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Review

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20 pages, 4292 KiB  
Review
Polyamidoamine Dendrimers for Enhanced Solubility of Small Molecules and Other Desirable Properties for Site Specific Delivery: Insights from Experimental and Computational Studies
by Daniel M. Shadrack, Hulda S. Swai, Joan J. E. Munissi, Egid B. Mubofu and Stephen S. Nyandoro
Molecules 2018, 23(6), 1419; https://doi.org/10.3390/molecules23061419 - 12 Jun 2018
Cited by 44 | Viewed by 8234
Abstract
Clinical applications of many small molecules are limited due to poor solubility and lack of controlled release besides lack of other desirable properties. Experimental and computational studies have reported on the therapeutic potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers in pre-clinical and [...] Read more.
Clinical applications of many small molecules are limited due to poor solubility and lack of controlled release besides lack of other desirable properties. Experimental and computational studies have reported on the therapeutic potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers in pre-clinical and clinical settings. Besides formulation strategies, factors such as pH, PAMAM dendrimer generation, PAMAM dendrimer concentration, nature of the PAMAM core, special ligand and surface modifications of PAMAM dendrimer have an influence on drug solubility and other recommendable pharmacological properties. This review, therefore, compiles the recently reported applications of PAMAM dendrimers in pre-clinical and clinical uses as enhancers of solubility and other desirable properties such as sustained and controlled release, bioavailability, bio-distribution, toxicity reduction or enhancement, and targeted delivery of small molecules with emphasis on cancer treatment. Full article
(This article belongs to the Special Issue Dendrimers in Medicine)
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13 pages, 3251 KiB  
Review
The ABP Dendrimer, a Drug-Candidate against Inflammatory Diseases That Triggers the Activation of Interleukin-10 Producing Immune Cells
by Séverine Fruchon and Rémy Poupot
Molecules 2018, 23(6), 1272; https://doi.org/10.3390/molecules23061272 - 25 May 2018
Cited by 20 | Viewed by 4536
Abstract
The ABP dendrimer, which is built on a phosphorus-based scaffold and bears twelve azabisphosphonate groups at its surface, is one of the dendrimers that has been shown to display immuno-modulatory and anti-inflammatory effects towards the human immune system. Its anti-inflammatory properties have been [...] Read more.
The ABP dendrimer, which is built on a phosphorus-based scaffold and bears twelve azabisphosphonate groups at its surface, is one of the dendrimers that has been shown to display immuno-modulatory and anti-inflammatory effects towards the human immune system. Its anti-inflammatory properties have been successfully challenged in animal models of inflammatory disorders. In this review, we trace the discovery and the evaluation of the therapeutic effects of the ABP dendrimer in three different animal models of both acute and chronic inflammatory diseases. We emphasize that its therapeutic effects rely on the enhancement of the production of Interleukin-10, the paradigm of anti-inflammatory cytokines, by different subsets of immune cells, such as monocytes/macrophages and CD4+ T lymphocytes. Full article
(This article belongs to the Special Issue Dendrimers in Medicine)
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29 pages, 1670 KiB  
Review
Function Oriented Molecular Design: Dendrimers as Novel Antimicrobials
by Sandra García-Gallego, Gianluigi Franci, Annarita Falanga, Rafael Gómez, Veronica Folliero, Stefania Galdiero, Francisco Javier De la Mata and Massimiliano Galdiero
Molecules 2017, 22(10), 1581; https://doi.org/10.3390/molecules22101581 - 21 Sep 2017
Cited by 53 | Viewed by 8553
Abstract
In recent years innovative nanostructures are attracting increasing interest and, among them, dendrimers have shown several fields of application. Dendrimers can be designed and modified in plentiful ways giving rise to hundreds of different molecules with specific characteristics and functionalities. Biomedicine is probably [...] Read more.
In recent years innovative nanostructures are attracting increasing interest and, among them, dendrimers have shown several fields of application. Dendrimers can be designed and modified in plentiful ways giving rise to hundreds of different molecules with specific characteristics and functionalities. Biomedicine is probably the field where these molecules find extraordinary applicability, and this is probably due to their multi-valency and to the fact that several other chemicals can be coupled to them to obtain desired compounds. In this review we will describe the different production strategies and the tools and technologies for the study of their characteristics. Finally, we provide a panoramic overview of their applications to meet biomedical needs, especially their use as novel antimicrobials. Full article
(This article belongs to the Special Issue Dendrimers in Medicine)
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22 pages, 7281 KiB  
Review
Radiolabeled Dendrimers for Nuclear Medicine Applications
by Lingzhou Zhao, Meilin Zhu, Yujie Li, Yan Xing and Jinhua Zhao
Molecules 2017, 22(9), 1350; https://doi.org/10.3390/molecules22091350 - 25 Aug 2017
Cited by 30 | Viewed by 7659
Abstract
Recent advances in nuclear medicine have explored nanoscale carriers for targeted delivery of various radionuclides in specific manners to improve the effect of diagnosis and therapy of diseases. Due to the unique molecular architecture allowing facile attachment of targeting ligands and radionuclides, dendrimers [...] Read more.
Recent advances in nuclear medicine have explored nanoscale carriers for targeted delivery of various radionuclides in specific manners to improve the effect of diagnosis and therapy of diseases. Due to the unique molecular architecture allowing facile attachment of targeting ligands and radionuclides, dendrimers provide versatile platforms in this filed to build abundant multifunctional radiolabeled nanoparticles for nuclear medicine applications. This review gives special focus to recent advances in dendrimer-based nuclear medicine agents for the imaging and treatment of cancer, cardiovascular and other diseases. Radiolabeling strategies for different radionuclides and several challenges involved in clinical translation of radiolabeled dendrimers are extensively discussed. Full article
(This article belongs to the Special Issue Dendrimers in Medicine)
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21 pages, 1316 KiB  
Review
Dendrimers as Nanocarriers for Nucleic Acid and Drug Delivery in Cancer Therapy
by Livia Palmerston Mendes, Jiayi Pan and Vladimir P. Torchilin
Molecules 2017, 22(9), 1401; https://doi.org/10.3390/molecules22091401 - 23 Aug 2017
Cited by 549 | Viewed by 17876
Abstract
Dendrimers are highly branched polymers with easily modifiable surfaces. This makes them promising structures for functionalization and also for conjugation with drugs and DNA/RNA. Their architecture, which can be controlled by different synthesis processes, allows the control of characteristics such as shape, size, [...] Read more.
Dendrimers are highly branched polymers with easily modifiable surfaces. This makes them promising structures for functionalization and also for conjugation with drugs and DNA/RNA. Their architecture, which can be controlled by different synthesis processes, allows the control of characteristics such as shape, size, charge, and solubility. Dendrimers have the ability to increase the solubility and bioavailability of hydrophobic drugs. The drugs can be entrapped in the intramolecular cavity of the dendrimers or conjugated to their functional groups at their surface. Nucleic acids usually form complexes with the positively charged surface of most cationic dendrimers and this approach has been extensively employed. The presence of functional groups in the dendrimer’s exterior also permits the addition of other moieties that can actively target certain diseases and improve delivery, for instance, with folate and antibodies, now widely used as tumor targeting strategies. Dendrimers have been investigated extensively in the medical field, and cancer treatment is one of the greatest areas where they have been most used. This review will consider the main types of dendrimer currently being explored and how they can be utilized as drug and gene carriers and functionalized to improve the delivery of cancer therapy. Full article
(This article belongs to the Special Issue Dendrimers in Medicine)
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