Developments in Treatment Methodologies Using Dendrimers for Infectious Diseases (original) (raw)
Related papers
2007
Nearly 3 decades ago, a dendritic structure was stepwise synthesized for the first time as a new type of molecules with promising applications. During years a huge effort has been devoted to implement the synthetic skills concerning the synthesis of these molecules and especially, new methods for purification and characterization of these compounds that are in the nanoscale range. The chemical manipulation of the surface and inner core of dendrimers were strategically used to allow a tailor-made control of physical-chemical properties and to discover new applications in material science and biomedicine. Although several examples have been reported in the literature describing applications of functionalized dendrimers and acclaiming a key role of these molecules, very scarce examples are actually close to the market. This review summarizes the state of the art of dendrimers and dendritic polymers as anti-infective agents, with a special focus on the strategies to block receptors used by pathogens for attachment, cell entry and dissemination. These nanometre size molecules are very attractive compounds as new drugs easily to be manipulated to improve their activity and scope. This is already a very active area of research, where we are involved, with interesting potential as demonstrated by the Phase I clinical trial of a functionalized dendrimer with real possibilities to reach the market soon. The success of this compound should provoke an enormous stimulus to scientists working in this area as well as in the industrial companies for investment in this topic.
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 ...
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.
Application of Dendrimers for the Treatment of Infectious Diseases
Molecules
Dendrimers are drug delivery systems that are characterized by a three-dimensional, star-shaped, branched macromolecular network. They possess ideal properties such as low polydispersity index, biocompatibility and good water solubility. They are made up of the interior and the exterior layers. The exterior layer consists of functional groups that are useful for conjugation of drugs and targeting moieties. The interior layer exhibits improved drug encapsulation efficiency, reduced drug toxicity, and controlled release mechanisms. These unique properties make them useful for drug delivery. Dendrimers have attracted considerable attention as drug delivery system for the treatment of infectious diseases. The treatment of infectious diseases is hampered severely by drug resistance. Several properties of dendrimers such as their ability to overcome drug resistance, toxicity and control the release mechanism of the encapsulated drugs make them ideal systems for the treatment of infectious...
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 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.
Biological properties of low molecular mass peptide dendrimers
International Journal of Pharmaceutics, 2006
A series of new, low molecular mass, lysine-based peptide dendrimers with varying distribution of cationic and aromatic groups in the structure were synthesized. They expressed antimicrobial activity against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria as well as against fungal pathogens (Candida albicans). Their cytotoxic, haematotoxic and genotoxic effects were studied. It appears that steric distribution and type od hydrophobic (aromatic) groups and cationic centres are important components of dendrimeric structure and influence both antimicrobial potency and toxicity. Such 3D structure of our dendrimers mimics that of the natural antimicrobial peptides and can be achieved by application of dendrimer chemistry.
Dendrimers as Biopharmaceuticals: Synthesis and Properties
Current Topics in Medicinal Chemistry, 2008
Two general aspects which need to be considered for the successful application of dendrimers for biomedical purposes are their availability at an acceptable cost and their suitability as regards their pharmacodynamic and pharmacokinetic properties. These two aspects are covered in this review. In the first part, synthetic strategies for the preparation of dendrimers are outlined and emphasis is given to recent work on methodologies whose aim is the development of more efficient routes to dendrimers in terms of the materials used for their synthesis as well as in terms of the procedures required for their purification. These include procedures involving double-stage and double exponential synthesis, orthogonal coupling strategies, self-assembly and solid-phase approaches, as well as particularly useful synthetic protocols such as those used in "click chemistry". The second part of the review deals with the way in which the size, chemical constitution and physicochemical properties of dendrimers used for drug delivery may affect pharmacodynamic and pharmacokinetic parameters which are important considerations for drug bioavailability. This is illustrated by an overview of examples from recent work involving non-steroidal anti-inflammatory drugs, anticancer drugs and antibacterials.
A Review about Dendrimers: Synthesis, Types, Characterization and Applications
This review provides brief information concerning with the dendrimer, its synthesis, characterization and application in drug delivery. Dendrimer consist of well defined size, shape, molecular weight and monodispersity. These properties formulate the dendrimers a suitable carrier in drug delivery application. Dendrimer are built from number of molecular entities of colloidal paticles that exists in equilibrium with the molecules or ions in nature and due to this increases the solubility of poorly soluble drugs. Due to their distinct structural design these have improved physical and chemical properties. The compatibility between DNA, heparin and polyanions make them more versatile. Self assembly of molecules produces a quicker means of producing nanoscopic functional and structural systems. But the genuine effectiveness in drug delivery can be assessed only after accepting their behavior in vivo. Studies have explored the biological possiblities of dendrimers such as to transportation of genes, development of vaccines, antiviral, antibacterial and anticancer therapies. This review also describes how the dendrimer interrelate with numerous drugs and the prospective of these macromolecules in addition with the drug nanocarriers in transdermal route of administration, ocular, respiratory, oral and intravenous administration. Dendrimers assure superior prospect protrusion for the biomedicine. This review provides a brief discussion of dendrimers' physico-chemical properties and their potential use in a range of areas of research, technology and treatment.
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.