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Pharmaceutics
Special Issues
Recent Advances in Dendrimer Nanomedicine
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Recent Advances in Dendrimer Nanomedicine

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 17224

Special Issue Editor

Dr. Nina Filipczak

E-Mail Website
Guest Editor
Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA
Interests: dendrimers; drug delivery systems; nanomedicine; cancer biology; cancer drug resistance

Special Issue Information

Dear Colleagues,

The field of drug delivery systems is facing a need for nontoxic, nonimmunogenic, and biodegradable polymers. In addition to these qualities, low polydispersity and replaceable functional groups are also needed. Dendrimers are best suited for this task in comparison to other polymeric options. The property of having many functional groups on the surface of the dendrimer creates an enormous number of possibilities in the synthesis of new dendrimer-based therapies. This Special Issue aims to collect a plethora of papers that cover the use of dendrimers in the pharmaceutical industry from drug delivery formulations to diagnostic tools. Dendrimers have been explored for many years and therefore we decided to make an updated review of the field with a special focus on the translational aspect from bench to clinic. I am pleased to announce that in this Special Issue, original research articles and reviews that highlight recent advances and the state of the art in the field of dendrimers are welcome.

I look forward to receiving your contributions.

Dr. Nina Filipczak
Guest Editor

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 submissions that pass pre-check are 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. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • dendrimers
  • drug delivery
  • surface modification
  • dendrimer-based polyplex system
  • multifunctional carrier
  • diagnostic tools
  • polymer therapeutics

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Published Papers (5 papers)

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Research

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22 pages, 3820 KiB  
Article
Dendrimer-Conjugated nSMase2 Inhibitor Reduces Tau Propagation in Mice
by Carolyn Tallon, Benjamin J. Bell, Anjali Sharma, Arindom Pal, Medhinee M. Malvankar, Ajit G. Thomas, Seung-Wan Yoo, Kristen R. Hollinger, Kaleem Coleman, Elizabeth L. Wilkinson, Sujatha Kannan, Norman J. Haughey, Rangaramanujam M. Kannan, Rana Rais and Barbara S. Slusher
Pharmaceutics 2022, 14(10), 2066; https://doi.org/10.3390/pharmaceutics14102066 - 28 Sep 2022
Cited by 14 | Viewed by 3179
Abstract
Alzheimer’s disease (AD) is characterized by the progressive accumulation of amyloid-β and hyperphosphorylated tau (pTau), which can spread throughout the brain via extracellular vesicles (EVs). Membrane ceramide enrichment regulated by the enzyme neutral sphingomyelinase 2 (nSMase2) is a critical component of at least [...] Read more.
Alzheimer’s disease (AD) is characterized by the progressive accumulation of amyloid-β and hyperphosphorylated tau (pTau), which can spread throughout the brain via extracellular vesicles (EVs). Membrane ceramide enrichment regulated by the enzyme neutral sphingomyelinase 2 (nSMase2) is a critical component of at least one EV biogenesis pathway. Our group recently identified 2,6-Dimethoxy-4-(5-Phenyl-4-Thiophen-2-yl-1H-Imidazol-2-yl)-Phenol (DPTIP), the most potent (30 nM) and selective inhibitor of nSMase2 reported to date. However, DPTIP exhibits poor oral pharmacokinetics (PK), modest brain penetration, and rapid clearance, limiting its clinical translation. To enhance its PK properties, we conjugated DPTIP to a hydroxyl-PAMAM dendrimer delivery system, creating dendrimer-DPTIP (D-DPTIP). In an acute brain injury model, orally administered D-DPTIP significantly reduced the intra-striatal IL-1β-induced increase in plasma EVs up to 72 h post-dose, while oral DPTIP had a limited effect. In a mouse tau propagation model, where a mutant hTau (P301L/S320F) containing adeno-associated virus was unilaterally seeded into the hippocampus, oral D-DPTIP (dosed 3× weekly) significantly inhibited brain nSMase2 activity and blocked the spread of pTau to the contralateral hippocampus. These data demonstrate that dendrimer conjugation of DPTIP improves its PK properties, resulting in significant inhibition of EV propagation of pTau in mice. Dendrimer-based delivery of DPTIP has the potential to be an exciting new therapeutic for AD. Full article
(This article belongs to the Special Issue Recent Advances in Dendrimer Nanomedicine)
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17 pages, 2301 KiB  
Article
In Vitro Interactions of Amphiphilic Phosphorous Dendrons with Liposomes and Exosomes—Implications for Blood Viscosity Changes
by Martina Veliskova, Milan Zvarik, Simon Suty, Juraj Jacko, Patrick Mydla, Katarina Cechova, Daniela Dzubinska, Marcela Morvova, Maksim Ionov, Maria Terehova, Jean-Pierre Majoral, Maria Bryszewska and Iveta Waczulikova
Pharmaceutics 2022, 14(8), 1596; https://doi.org/10.3390/pharmaceutics14081596 - 30 Jul 2022
Cited by 2 | Viewed by 2428
Abstract
Drug delivery by dendron-based nanoparticles is widely studied due to their ability to encapsulate or bind different ligands. For medical purposes, it is necessary (even if not sufficient) for these nanostructures to be compatible with blood. We studied the interaction of amphiphilic dendrons [...] Read more.
Drug delivery by dendron-based nanoparticles is widely studied due to their ability to encapsulate or bind different ligands. For medical purposes, it is necessary (even if not sufficient) for these nanostructures to be compatible with blood. We studied the interaction of amphiphilic dendrons with blood samples from healthy volunteers using standard laboratory methods and rheological measurements. We did not observe clinically relevant abnormalities, but we found a concentration-dependent increase in whole blood viscosity, higher in males, presumably due to the formation of aggregates. To characterize the nature of the interactions among blood components and dendrons, we performed experiments on the liposomes and exosomes as models of biological membranes. Based on results obtained using diverse biophysical methods, we conclude that the interactions were of electrostatic nature. Overall, we have confirmed a concentration-dependent effect of dendrons on membrane systems, while the effect of generation was ambiguous. At higher dendron concentrations, the structure of membranes became disturbed, and membranes were prone to forming bigger aggregates, as visualized by SEM. This might have implications for blood flow disturbances when used in vivo. We propose to introduce blood viscosity measurements in early stages of investigation as they can help to optimize drug-like properties of potential drug carriers. Full article
(This article belongs to the Special Issue Recent Advances in Dendrimer Nanomedicine)
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15 pages, 5019 KiB  
Article
Co-Delivery of siRNA and Chemotherapeutic Drug Using 2C5 Antibody-Targeted Dendrimer-Based Mixed Micelles for Multidrug Resistant Cancers
by Satya Siva Kishan Yalamarty, Nina Filipczak, Xiang Li, Tanvi Vinod Pathrikar, Colin Cotter and Vladimir P. Torchilin
Pharmaceutics 2022, 14(7), 1470; https://doi.org/10.3390/pharmaceutics14071470 - 15 Jul 2022
Cited by 20 | Viewed by 3229
Abstract
Multidrug resistance (MDR) observed in tumors significantly hinders the efficacy of chemotherapy. Downregulation of efflux proteins, such as P-glycoprotein (P-gp), using small interfering RNA (siRNA) can be an effective way to minimize the resistance in tumors. In this study, monoclonal antibody 2C5 (mAb [...] Read more.
Multidrug resistance (MDR) observed in tumors significantly hinders the efficacy of chemotherapy. Downregulation of efflux proteins, such as P-glycoprotein (P-gp), using small interfering RNA (siRNA) can be an effective way to minimize the resistance in tumors. In this study, monoclonal antibody 2C5 (mAb 2C5)-PEG7k-DOPE conjugates were post-inserted into the mixed dendrimer micelles containing generation 4 (G4) polyamidoamine (PAMAM)-PEG2k-DOPE and PEG5k-DOPE. The inherent amphiphilic nature of DOPE conjugates causes the copolymers to self-assemble to form a micelle, which can encapsulate hydrophobic chemotherapeutic drugs in its core. The siRNA electrostatically binds to the cationic charges on the G4 PAMAM dendrimer. The tumor-specific mAb 2C5 on the surface of these nano-preparations resulted in improved tumor targeting. This active targeting to tumors can cause increase in the drug and siRNA accumulation at the tumor site, and thereby minimizing the off-target effects. The micelles were shown to have higher cellular association and effectiveness in vitro. The immunomicelle preparation was also tested for cytotoxicity in breast (MDA-MB-231) and ovarian (SKOV-3TR) MDR cancer cell lines. Full article
(This article belongs to the Special Issue Recent Advances in Dendrimer Nanomedicine)
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Review

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37 pages, 1117 KiB  
Review
Safety Challenges and Application Strategies for the Use of Dendrimers in Medicine
by Xiang Li, Abid Naeem, Shanghua Xiao, Lei Hu, Jing Zhang and Qin Zheng
Pharmaceutics 2022, 14(6), 1292; https://doi.org/10.3390/pharmaceutics14061292 - 17 Jun 2022
Cited by 55 | Viewed by 4823
Abstract
Dendrimers are used for a variety of applications in medicine but, due to their host–guest and entrapment characteristics, are particularly used for the delivery of genes and drugs. However, dendrimers are intrinsically toxic, thus creating a major limitation for their use in biological [...] Read more.
Dendrimers are used for a variety of applications in medicine but, due to their host–guest and entrapment characteristics, are particularly used for the delivery of genes and drugs. However, dendrimers are intrinsically toxic, thus creating a major limitation for their use in biological systems. To reduce such toxicity, biocompatible dendrimers have been designed and synthesized, and surface engineering has been used to create advantageous changes at the periphery of dendrimers. Although dendrimers have been reviewed previously in the literature, there has yet to be a systematic and comprehensive review of the harmful effects of dendrimers. In this review, we describe the routes of dendrimer exposure and their distribution in vivo. Then, we discuss the toxicity of dendrimers at the organ, cellular, and sub-cellular levels. In this review, we also describe how technology can be used to reduce dendrimer toxicity, by changing their size and surface functionalization, how dendrimers can be combined with other materials to generate a composite formulation, and how dendrimers can be used for the diagnosis of disease. Finally, we discuss future challenges, developments, and research directions in developing biocompatible and safe dendrimers for medical purposes. Full article
(This article belongs to the Special Issue Recent Advances in Dendrimer Nanomedicine)
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28 pages, 38259 KiB  
Review
Dendrimers as Antiamyloid Agents
by Svetlana A. Sorokina and Zinaida B. Shifrina
Pharmaceutics 2022, 14(4), 760; https://doi.org/10.3390/pharmaceutics14040760 - 31 Mar 2022
Cited by 18 | Viewed by 2774
Abstract
Dendrimer–protein conjugates have significant prospects for biological applications. The complexation changes the biophysical behavior of both proteins and dendrimers. The dendrimers could influence the secondary structure of proteins, zeta-potential, distribution of charged regions on the surface, the protein–protein interactions, etc. These changes offer [...] Read more.
Dendrimer–protein conjugates have significant prospects for biological applications. The complexation changes the biophysical behavior of both proteins and dendrimers. The dendrimers could influence the secondary structure of proteins, zeta-potential, distribution of charged regions on the surface, the protein–protein interactions, etc. These changes offer significant possibilities for the application of these features in nanotheranostics and biomedicine. Based on the dendrimer–protein interactions, several therapeutic applications of dendrimers have emerged. Thus, the formation of stable complexes retains the disordered proteins on the aggregation, which is especially important in neurodegenerative diseases. To clarify the origin of these properties and assess the efficiency of action, the mechanism of protein–dendrimer interaction and the nature and driving force of binding are considered in this review. The review outlines the antiamyloid activity of dendrimers and discusses the effect of dendrimer structures and external factors on their antiamyloid properties. Full article
(This article belongs to the Special Issue Recent Advances in Dendrimer Nanomedicine)
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