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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 -
Molecules (Basel, Switzerland) Apr 2018Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of... (Review)
Review
Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine) (PAMAM) dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i) formulation and (ii) nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices.
Topics: Dendrimers; Drug Delivery Systems; Drug Liberation; Indomethacin; Resveratrol; Stilbenes
PubMed: 29670005
DOI: 10.3390/molecules23040938 -
Molecules (Basel, Switzerland) May 2016The main objective of this review is to describe the importance of dendrimer prodrugs in the design of new drugs, presenting numerous applications of these... (Review)
Review
The main objective of this review is to describe the importance of dendrimer prodrugs in the design of new drugs, presenting numerous applications of these nanocomposites in the pharmaceutical field. Therefore, the use of dendrimer prodrugs as carrier for drug delivery, to improve pharmacokinetic properties of prototype, to promote drug sustained-release, to increase selectivity and, consequently, to decrease toxicity, are just some examples of topics that have been extensively reported in the literature, especially in the last decade. The examples discussed here give a panel of the growing interest dendrimer prodrugs have been evoking in the scientific community.
Topics: Dendrimers; Drug Delivery Systems; Drug Design; Humans; Prodrugs
PubMed: 27258239
DOI: 10.3390/molecules21060686 -
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 -
Monoclonal Antibodies in... Oct 2017Dendrimers are unimolecular architectural nano- or microparticle entities that can accommodate various nutraceuticals and pharmaceuticals between their branches... (Review)
Review
Dendrimers are unimolecular architectural nano- or microparticle entities that can accommodate various nutraceuticals and pharmaceuticals between their branches (dendrons) and provide targeted delivery of biomimetics into different tissues upon addition of functionalized groups to the dendrimer's surface. Covalent binding, hydrogen bonds, and electrostatic interactions between dendrimer-composing molecules are known to form and stabilize dendrimer structure. Carotenoids have recently been shown to form dendrimer-like structures and promote targeted delivery of "cargo" molecules into organs characterized by high-carotenoid uptake (adrenal glands, prostate, liver, and brain). The use of carotenoid dendrimers, in particular lycosome particles loaded with various xenobiotics (resveratrol, cocoa flavanols, and HMG-CoA reductase inhibitors), reportedly has a beneficial effect in diabetic foot syndrome, prehypertension, and cardiovascular disease. New applications for carotenoid dendrimers may arise from the use of complexes formed by carotenoid dendrimers and monoclonal antibodies (mAbs). The internalization of carotenoid dendrimer-mAb complexes through receptor-mediated mechanisms may prevent interactions of dendrimer-incorporated xenobiotics with membrane-associated P-glycoprotein, a major factor of drug resistance in tumor cells. The incorporation of mAb fragments with higher binding capacity to the membrane receptors and higher affinity to the target molecule may further increase the bioavailability of "cargo" molecules transported by the carotenoid dendrimer-mAb complexes and open new doors in nanodelivery technologies.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Adrenal Glands; Antibodies, Monoclonal; Brain; Carotenoids; Dendrimers; Drug Carriers; Drug Resistance, Neoplasm; Humans; Liver; Male; Neoplasms; Prostate
PubMed: 28994638
DOI: 10.1089/mab.2017.0032 -
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 -
Molecules (Basel, Switzerland) Aug 2016This special issue entitled "Functional Dendrimers" focuses on the manipulation of at least six "critical nanoscale design parameters" (CNDPs) of dendrimers including:...
This special issue entitled "Functional Dendrimers" focuses on the manipulation of at least six "critical nanoscale design parameters" (CNDPs) of dendrimers including: size, shape, surface chemistry, flexibility/rigidity, architecture and elemental composition. These CNDPs collectively define properties of all "functional dendrimers". This special issue contains many interesting examples describing the manipulation of certain dendrimer CNDPs to create new emerging properties and, in some cases, predictive nanoperiodic property patterns (i.e., dendritic effects). The systematic engineering of CNDPs provides a valuable strategy for optimizing functional dendrimer properties for use in specific applications.
Topics: Dendrimers; Periodicals as Topic
PubMed: 27517890
DOI: 10.3390/molecules21081035 -
Drug Discovery Today May 2016Despite low prevalence, brain tumors are one of the most lethal forms of cancer. Unfortunately the blood-brain barrier (BBB), a highly regulated, well coordinated and... (Review)
Review
Despite low prevalence, brain tumors are one of the most lethal forms of cancer. Unfortunately the blood-brain barrier (BBB), a highly regulated, well coordinated and efficient barrier, checks the permeation of most of the drugs across it. Hence, crossing this barrier is one of the most significant challenges in the development of efficient central nervous system therapeutics. Surface-engineered dendrimers improve biocompatibility, drug-release kinetics and aptitude to target the BBB and/or tumors and facilitate transportation of anticancer bioactives across the BBB. This review sheds light on different aspects of brain tumors and dendrimers based on different approaches for treatment including recent research, opportunities and challenges encountered in development of novel and efficient dendrimer-based therapeutics for the treatment of brain tumors.
Topics: Animals; Blood-Brain Barrier; Brain Neoplasms; Dendrimers; Drug Carriers; Humans; Nanostructures
PubMed: 26891979
DOI: 10.1016/j.drudis.2016.02.006