Dendrimers and dendritic polymers as anti-infective agents: New antimicrobial strategies for therapeutic drugs (original) (raw)
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Function Oriented Molecular Design: Dendrimers as Novel Antimicrobials
Molecules, 2017
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.
Dendrimers in biomedical applications—reflections on the field
Advanced Drug Delivery Reviews, 2012
The formation of particulate systems with well-defined sizes and shapes is of eminent interest in certain medical applications such as drug delivery, gene transfection, and imaging. The high level of control possible over the architectural design of dendrimers; their size, shape, branching length/density, and their surface functionality, clearly distinguishes these structures as unique and optimum carriers in those applications. The bioactive agents may be encapsulated into the interior of the dendrimers or chemically attached/physically adsorbed onto the dendrimer surface, with the option of tailoring the carrier to the specific needs of the active material and its therapeutic applications. In this regard, the high density of exo-presented surface groups allows attachment of targeting groups or functionality that may modify the solution behavior or toxicity of dendrimers. Quite remarkably, modified dendrimers have been shown to act as nano-drugs against tumors, bacteria, and viruses. Recent successes in simplifying and optimizing the synthesis of dendrimers such as the 'lego' and 'click' approaches, provide a large variety of structures while at the same time reducing the cost of their production. The reflections on biomedical applications of dendrimers given in this review clearly demonstrate the potential of this new fourth major class of polymer architecture and indeed substantiate the high hopes for the future of dendrimers.
Developments in Treatment Methodologies Using Dendrimers for Infectious Diseases
Molecules, 2021
Dendrimers comprise a specific group of macromolecules, which combine structural properties of both single molecules and long expanded polymers. The three-dimensional form of dendrimers and the extensive possibilities for use of additional substrates for their construction creates a multivalent potential and a wide possibility for medical, diagnostic and environmental purposes. Depending on their composition and structure, dendrimers have been of interest in many fields of science, ranging from chemistry, biotechnology to biochemical applications. These compounds have found wide application from the production of catalysts for their use as antibacterial, antifungal and antiviral agents. Of particular interest are peptide dendrimers as a medium for transport of therapeutic substances: synthetic vaccines against parasites, bacteria and viruses, contrast agents used in MRI, antibodies and genetic material. This review focuses on the description of the current classes of dendrimers, the...
Surface-Engineered Dendrimers: a Solution for Toxicity Issues
Journal of Biomaterials Science-polymer Edition, 2009
The nature of the groups that reside on the periphery of dendrimers and have contact with the surrounding media is the primary factor that controls the surface-related physico-chemical characteristics of these macromolecules. Therefore, transformation/tailoring of the peripheral functionalities of dendrimers is an economical way to change the overall behaviour of a particular dendrimer class or to impart new properties. In addition, the yields of the completely modified macromolecules could provide valuable information for the accessibility and the back folding of the moieties placed at the dendritic surfaces. The present article reviews the parent toxicity issues associated with cationic dendrimers like PAMAM and PPI, and examines the possibility of addressing this aspect through surface engineering with conjugation of biocompatible molecules. compounds has found recent applications in the biomedical area to substitute standard means for the distribution of medical therapeutics .
Commentary Dendrimers in biomedical applications—reflections on the field B
The formation of particulate systems with well-defined sizes and shapes is of eminent interest in certain medical applications such as drug delivery, gene transfection, and imaging. The high level of control possible over the architectural design of dendrimers; their size, shape, branching length/density, and their surface functionality, clearly distinguishes these structures as unique and optimum carriers in those applications. The bioactive agents may be encapsulated into the interior of the dendrimers or chemically attached/physically adsorbed onto the dendrimer surface, with the option of tailoring the carrier to the specific needs of the active material and its therapeutic applications. In this regard, the high density of exo-presented surface groups allows attachment of targeting groups or functionality that may modify the solution behavior or toxicity of dendrimers. Quite remarkably, modified dendrimers have been shown to act as nano-drugs against tumors, bacteria, and viruses. Recent successes in simplifying and optimizing the synthesis of dendrimers such as the dlegoT and dclickT approaches, provide a large variety of structures while at the same time reducing the cost of their production. The reflections on biomedical applications of dendrimers given in this review clearly demonstrate the potential of this new fourth major class of polymer architecture and indeed substantiate the high hopes for the future of dendrimers. D 2005 Published by Elsevier B.V.
Dendrimers--revolutionary drugs for infectious diseases
Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
Over recent years innovative nanomolecules in a form of dendrimers have been gaining increasing interest. These compounds can be designed and modified in many ways giving a molecule which meets required expectations. For this reason dendrimers are the object of intensive studies in many fields of nanoscience including one of the most thriving--biomedicine. Numerous studies provide evidence that some dendrimers exhibit activities against many species/strains of viruses, bacteria, fungi, and prions. These types of dendritic nanostructures which are distinguished by antipathogenic properties and low cytotoxicity to eukaryotic cells may be potentially applied in medicine as novel drugs for various infectious diseases, especially those which are persistent, marked by high mortality rate, or untreatable. Dendrimers can exert their effect via different mechanisms of action, which are, in most cases, related to multivalency of the nanomolecule. The application of dendrimers is likely to be ...
Molecules (Basel, Switzerland), 2017
We report a versatile divergent methodology to construct dendrimers from a tetrafunctional core, utilizing the robust copper(I) catalyzed alkyne-azide cycloaddition (CuAAC, "click") reaction for both dendrimer synthesis and post-synthesis functionalization. Dendrimers of generations 1-3 with 8-32 protected or free OH and acetylene surface groups, were synthesized using building blocks that included acetylene- or azide-terminated molecules with carboxylic acid or diol end groups, respectively. The acetylene surface groups were subsequently used to covalently link cationic amino groups. A preliminary evaluation indicated that the generation one dendrimer with terminal NH₃⁺ groups was the most effective bactericide, and it was more potent than several previously studied dendrimers. Our results suggest that size, functional end groups and hydrophilicity are important parameters to consider in designing efficient antimicrobial dendrimers.
DENDRIMER: NOVEL STRATEGIES FOR DRUG DELIVERY SYSTEM
The development of novel particulate systems with defined shapes and sizes is of prominent interest in certain therapeutic applications such as drug delivery, gene transfection, diagnostic and imaging. On controlling and designing optimized architectural design of dendrimers; their shape, size, branching pattern length/density, and their surface functionality, clearly discriminate these structures as inimitable and optimal hauler in those applications. Moderately modified dendrimers have been shown to act as nano-drugs adjacent to tumors, viruses and bacteria. Recent triumph in simplifying and optimizing the production of dendrimers make available a large variety of structures while simultaneously reducing the cost of their production. The reflections on biomedical applications of dendrimers given in this review clearly make obvious the impending of this new fourth major class of polymer structural design and undeniably prove the high expectation for the future of dendrimers.
DENDRIMERS: SYNTHESIS, PROPERTIES, BIOMEDICAL AND DRUG DELIVERY APPLICATIONS
Am J PharmTech Res, 2012
Dendrimers are a new class of polymeric materials. They are highly branched, monodisperse macromolecules. The structure of these materials has a great impact on their physical and chemical properties. As a result of their unique behaviour dendrimers are suitable for a wide range of targeted drug delivery, controlled drug delivery, gene delivery and industrial applications. The paper gives a concise review of dendrimers physico-chemical properties, types, synthetic pathway & their possible use in various aspects of research, technology and treatment of disease. Journal home page: http://www.ajptr.com/ Sougata et al.
Dendrimers as versatile platform in drug delivery applications
European Journal of Pharmaceutics and Biopharmaceutics, 2009
About forty percent of newly developed drugs are rejected by the pharmaceutical industry and will never benefit a patient because of poor bioavailability due to low water solubility and/or cell membrane permeability. New delivery technologies could help to overcome this challenge. Nanostructures with uniform and well-defined particle size and shape are of eminent interest in biomedical applications because of their ability to cross cell membranes and to reduce the risk of premature clearance from the body. The high level of control over the dendritic architecture (size, branching density, surface functionality) makes dendrimers ideal carriers in these applications. Many commercial small molecule drugs with anticancer, anti-inflammatory, and antimicrobial activity have been successfully associated with dendrimers such as poly(amidoamine) (PAMAM), poly(propylene imine) (PPI or DAB) and poly(etherhydroxylamine) (PEHAM) dendrimers, either via physical interactions or through chemical bonding ('prodrug approach'). Targeted delivery is possible via targeting ligands conjugated to the dendrimer surface or via the enhanced permeability and retention (EPR) effect. The biocompatibility of dendrimers follows patterns known from other small particles. Cationic surfaces show cytotoxicity; however, derivatization with fatty acid or PEG chains, reducing the overall charge density and minimizing contact between cell surfaces and dendrimers, can reduce toxic effects.