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Chemical Communications (Cambridge,... Dec 2023In recent years, dendrimer-based vesicles, known as dendrimersomes, have garnered significant attention as highly promising alternatives to lipid vesicles in a variety... (Review)
Review
In recent years, dendrimer-based vesicles, known as dendrimersomes, have garnered significant attention as highly promising alternatives to lipid vesicles in a variety of biomedical applications. Dendrimersomes offer several advantages, including relatively straightforward synthesis, non-immunogenic properties, stability in circulation, and minimal size variability. These vesicles are composed of Janus dendrimers, which are polymers characterized by two dendritic wedges with different terminal groups - hydrophilic and hydrophobic. This dendrimer structure enables the self-assembly of dendrimersomes. The purpose of this highlight is to provide an overview of recent advancements achieved through the utilization of biomimetic dendrimersomes in various biomedical applications such as drug and nucleic acid delivery.
Topics: Dendrimers; Polymers; Hydrophobic and Hydrophilic Interactions
PubMed: 37999927
DOI: 10.1039/d3cc03182a -
Biomolecules Aug 2019Drug delivery systems are molecular platforms in which an active compound is packed into or loaded on a biocompatible nanoparticle. Such a solution improves the activity... (Review)
Review
Drug delivery systems are molecular platforms in which an active compound is packed into or loaded on a biocompatible nanoparticle. Such a solution improves the activity of the applied drug or decreases its side effects. Dendrimers are promising molecular platforms for drug delivery due to their unique properties. These macromolecules are known for their defined size, shape, and molecular weight, as well as their monodispersity, the presence of the void space, tailorable structure, internalization by cells, selectivity toward cells and intracellular components, protection of guest molecules, and controllable release of the cargo. Dendrimers were tested as carriers of various molecules and, simultaneously, their toxicity was examined using different cell lines. It was discovered that, in general, dendrimer cytotoxicity depended on the generation, the number of surface groups, and the nature of terminal moieties (anionic, neutral, or cationic). Higher cytotoxicity occurred for higher-generation dendrimers and for dendrimers with positive charges on the surface. In order to decrease the cytotoxicity of dendrimers, scientists started to introduce different chemical modifications on the periphery of the nanomolecule. Dendrimers grafted with polyethylene glycol (PEG), acetyl groups, carbohydrates, and other moieties did not affect cell viability, or did so only slightly, while still maintaining other advantageous properties. Dendrimers clearly have great potential for wide utilization as drug and gene carriers. Moreover, some dendrimers have biological properties per se, being anti-fungal, anti-bacterial, or toxic to cancer cells without affecting normal cells. Therefore, intrinsic cytotoxicity is a comprehensive problem and should be considered individually depending on the potential destination of the nanoparticle.
Topics: Animals; Cytotoxins; Dendrimers; Drug Carriers; Humans
PubMed: 31374911
DOI: 10.3390/biom9080330 -
International Journal of Pharmaceutics Jan 2020Dendrimers are globular structures, presenting an initiator core, repetitive layers starting radially from the core and terminal groups on the surface, resembling tree... (Review)
Review
Dendrimers are globular structures, presenting an initiator core, repetitive layers starting radially from the core and terminal groups on the surface, resembling tree architecture. These structures have been studied in many biological applications, as drug, DNA, RNA and proteins delivery, as well as imaging and radiocontrast agents. With reference to that, this review focused in providing examples of dendrimers used in nanomedicine. Although most studies emphasize cancer, there are others which reveal action in the neurosystem, reducing either neuroinflammation or protein aggregation. Dendrimers can carry bioactive compounds by covalent bond (dendrimer prodrug), or by ionic interaction or adsortion in the internal space of the nanostructure. Additionally, dendrimers can be associated with other polymers, as PEG (polyethylene glycol), and with targeting structures as aptamers, antibodies, folic acid and carbohydrates. Their products in preclinical/clinical trial and those in the market are also discussed, with a total of six derivatives in clinical trials and seven products available in the market.
Topics: Antineoplastic Agents; Chemistry, Pharmaceutical; Clinical Trials as Topic; Contrast Media; Dendrimers; Humans; Nanomedicine; Nanostructures; Neoplasms; Nervous System Diseases; Polyethylene Glycols; Prodrugs; Protein Aggregation, Pathological
PubMed: 31759101
DOI: 10.1016/j.ijpharm.2019.118814 -
Macromolecular Bioscience Nov 2023Recently, several immunotherapeutic strategies are extensively studied and entered clinical investigation, suggesting their potential to lead a new generation of cancer... (Review)
Review
Recently, several immunotherapeutic strategies are extensively studied and entered clinical investigation, suggesting their potential to lead a new generation of cancer therapy. Particularly, a cancer vaccine that combines tumor-associated antigens and immune adjuvants with a nanocarrier holds huge promise for inducing specific antitumor immune responses. Hyperbranched polymers, such as dendrimers and branched polyethylenimine (PEI) possessing abundant positively charged amine groups and inherent proton sponge effect are ideal carriers of antigens. Much effort is devoted to design dendrimer/branched PEI-based cancer vaccines. Herein, the recent advances in the design of dendrimer/branched PEI-based cancer vaccines for immunotherapy are reviewed. The future perspectives with regard to the development of dendrimer/branched PEI-based cancer vaccines are also briefly discussed.
Topics: Humans; Cancer Vaccines; Dendrimers; Neoplasms; Immunotherapy; Polyethyleneimine; Polymers
PubMed: 37300444
DOI: 10.1002/mabi.202300188 -
Drug and Chemical Toxicology Sep 2022The development of molecular nanostructures with well-defined particle size and shape is of eminent interest in biomedicine. Among many studied nanostructures,...
The development of molecular nanostructures with well-defined particle size and shape is of eminent interest in biomedicine. Among many studied nanostructures, dendrimers represent the group of those most thoroughly characterized ones. Due to their unique structure and properties, dendrimers are very attractive for medical and pharmaceutical applications. Owing to the controllable cavities inside the dendrimer, guest molecules may be encapsulated, and highly reactive terminal groups are susceptible to further modifications, e.g., to facilitate target delivery. To understand the potential of these nanoparticles and to predict and avoid any adverse cellular reactions, it is necessary to know the mechanisms responsible for an efficient dendrimer uptake and the destination of their intracellular journey. In this article, we summarize the results of studies describing the dendrimer uptake, traffic, and efflux mechanisms depending on features of specific nanoparticles and cell types. We also present mechanisms of dendrimers responsible for toxicity and alteration in signal transduction pathways at the cellular level.
Topics: Dendrimers; Nanoparticles
PubMed: 33910437
DOI: 10.1080/01480545.2021.1915327 -
Current Drug Targets 2022In recent years, polymeric materials with the ability to self-assemble into micelles have been increasingly investigated for application in various fields, mainly in... (Review)
Review
In recent years, polymeric materials with the ability to self-assemble into micelles have been increasingly investigated for application in various fields, mainly in biomedicine. Micellar morphology is important and interesting in the field of drug transport and delivery since micelles can encapsulate hydrophobic molecules in their nucleus, improve the solubility of drugs, have active molecules in their outer layer, and, due to their nanometric size, they can take advantage of the EPR effect, prolong circulation time and avoid renal clearance. Furthermore, bioactive molecules (could be joined covalently or by host-host interaction), such as drugs, bioimaging molecules, proteins, targeting ligands, "cross-linkable" molecules, or linkages sensitive to internal or external stimuli, can be incorporated into them. The confined multivalent cooperativity and the ability to modify the dendritic structure provide versatility to create and improve the amphiphiles used in the micellar supramolecular field. As discussed in this review, the most studied structures are hybrid copolymers, which are formed by the combination of linear polymers and dendrons. Amphiphilic dendrimer micelles have achieved efficient and promising results in both in vitro and in vivo tests, and this encourages research for their future application in nanotherapies.
Topics: Antineoplastic Agents; Dendrimers; Drug Carriers; Drug Delivery Systems; Humans; Micelles; Polymers
PubMed: 34488581
DOI: 10.2174/1389450122666210906121803 -
Biomaterials Science Feb 2023Polyamidoamines (PAMAMs) are a class of dendrimer with monodispersity and controlled topology, which can deliver biologically active macromolecules (, genes and... (Review)
Review
Polyamidoamines (PAMAMs) are a class of dendrimer with monodispersity and controlled topology, which can deliver biologically active macromolecules (, genes and proteins) to specific regions with high efficiency and minimum side effects. In detail, PAMAMs can be functionalized easily by core modification or surface amendment to encapsulate a wide range of biomacromolecules. Besides, self-assembled, cross-linked and hybrid PAMAMs with customized therapeutic purposes are developed as delivery vehicles, which makes PAMAMs promising for biomacromolecule therapy. In this review, we comprehensively summarize the application of PAMAMs in biomacromolecule delivery from the synthesis of functionalized PAMAM carriers to the development of PAMAM-based drug delivery systems. The underlying strategies for PAMAM functionalization and assembly are first systematically discussed, and then the current applications of PAMAMs for biomacromolecule delivery are reviewed. Finally, a brief perspective on the further applications of PAMAMs concludes, aiming to provide insights into developing PAMAM-based biomacromolecule delivery systems.
Topics: Dendrimers; Drug Delivery Systems; Drug Carriers
PubMed: 36692071
DOI: 10.1039/d2bm01677j -
Advances in Colloid and Interface... May 2022Dendritic nanovectors-based drug delivery has gained significant attention in the past couple of decades. Dendrimers play a crucial role in deciding the solubility of... (Review)
Review
Dendritic nanovectors-based drug delivery has gained significant attention in the past couple of decades. Dendrimers play a crucial role in deciding the solubility of sparingly soluble drug molecules and help in improving pharmacokinetics. A few important steps in drug delivery through dendrimers, such as drug encapsulation, formulation, and target-specific delivery, play an important role in deciding the fate of a drug molecule. It is also of prime importance to understand the interactions between a drug molecule and dendrimers at atomistic levels to decode the mechanism of action of drug-dendrimer complexes and their reliability in terms of drug delivery. Colossal progress in current experimental and computational approaches in the field has resulted in a vast amount of data that needs to be curated to be further implemented efficiently. Improved computational power has led to greater accuracy and prompt predictions of properties of drug-dendrimer complexes and their mechanism of action. The current review encapsulates the pioneering work in the field, experimental achievements in terms of drug delivery, and newer computational techniques employed in the advancement of the field.
Topics: Dendrimers; Drug Delivery Systems; Pharmaceutical Preparations; Reproducibility of Results; Solubility
PubMed: 35339862
DOI: 10.1016/j.cis.2022.102639 -
Molecules (Basel, Switzerland) Sep 2020Biomedicine represents one of the main study areas for dendrimers, which have proven to be valuable both in diagnostics and therapy, due to their capacity for improving... (Review)
Review
Biomedicine represents one of the main study areas for dendrimers, which have proven to be valuable both in diagnostics and therapy, due to their capacity for improving solubility, absorption, bioavailability and targeted distribution. Molecular cytotoxicity constitutes a limiting characteristic, especially for cationic and higher-generation dendrimers. Antineoplastic research of dendrimers has been widely developed, and several types of poly(amidoamine) and poly(propylene imine) dendrimer complexes with doxorubicin, paclitaxel, imatinib, sunitinib, cisplatin, melphalan and methotrexate have shown an improvement in comparison with the drug molecule alone. The anti-inflammatory therapy focused on dendrimer complexes of ibuprofen, indomethacin, piroxicam, ketoprofen and diflunisal. In the context of the development of antibiotic-resistant bacterial strains, dendrimer complexes of fluoroquinolones, macrolides, beta-lactamines and aminoglycosides have shown promising effects. Regarding antiviral therapy, studies have been performed to develop dendrimer conjugates with tenofovir, maraviroc, zidovudine, oseltamivir and acyclovir, among others. Furthermore, cardiovascular therapy has strongly addressed dendrimers. Employed in imaging diagnostics, dendrimers reduce the dosage required to obtain images, thus improving the efficiency of radioisotopes. Dendrimers are macromolecular structures with multiple advantages that can suffer modifications depending on the chemical nature of the drug that has to be transported. The results obtained so far encourage the pursuit of new studies.
Topics: Animals; Anti-Inflammatory Agents; Biomedical Technology; Cell Death; Dendrimers; Diagnostic Imaging; Humans; Toxicity Tests
PubMed: 32882920
DOI: 10.3390/molecules25173982 -
Molecules (Basel, Switzerland) Sep 2020Nanostructured hyperbranched macromolecules have been extensively studied at the chemical, physical and morphological levels. The cellular structural and functional... (Review)
Review
Nanostructured hyperbranched macromolecules have been extensively studied at the chemical, physical and morphological levels. The cellular structural and functional complexity of neural cells and their cross-talk have made it rather difficult to evaluate dendrimer effects in a mixed population of glial cells and neurons. Thus, we are at a relatively early stage of bench-to-bedside translation, and this is due mainly to the lack of data valuable for clinical investigations. It is only recently that techniques have become available that allow for analyses of biological processes inside the living cells, at the nanoscale, in real time. This review summarizes the essential properties of neural cells and dendrimers, and provides a cross-section of biological, pre-clinical and early clinical studies, where dendrimers were used as nanocarriers. It also highlights some examples of biological studies employing dendritic polyglycerol sulfates and their effects on glia and neurons. It is the aim of this review to encourage young scientists to advance mechanistic and technological approaches in dendrimer research so that these extremely versatile and attractive nanostructures gain even greater recognition in translational medicine.
Topics: Animals; Anti-Inflammatory Agents; Brain; Brain Neoplasms; Dendrimers; Humans; Neurons
PubMed: 33007959
DOI: 10.3390/molecules25194489