DENDRIMER : FOR NOVEL DRUG DELIVERY SYSTEM- A REVIEW ARTICLE
Rameshwaram institute of Technology and management, Lucknow
Dendrimers have emerged as one of the most interesting themes for researchers as a result of unique functional architecture and macromolecular characteristics dendrimer, have attracted great attention in terms of biomedical applications. Although the PAMAMdendrimer has already been tested as a carrier for drugs and genes and as a contrast agent for bioimaging . This mini review highlights issues associated with the use of dendrimers as drug delivery vehicles. This article provides an insight into the structure, synthesis, properties,types and the applications of dendrimers in the bio-medical field.
Reference Id: PHARMATUTOR-ART-1427
In these formative years of nanotechnology, one of the most frequently seen names in the scientific literature is a class of polymerized macromolecules that carry the potential to provide the most exquisitely tailored forms and functions ever realized outside of nature. These polymerized macromolecules named as “dendrimers” are visualized as the polymers of 21st century. The term "dendrimer" is derived from the Greek words dendron, meaning tree and meros, meaning part. Dendrimers were introduced in 1980’s by Donald A. Tomalia, scientific director of the Center for Biologic Nanotechnology at the University of Michigan. Ideally, these are perfectly monodisperse macromolecules with a regular and highly branched three-dimensional architecture. Think of a tree in which each of its branches divides into two new branches after a certain length. This continues repeatedly until the branches become so densely packed that the canopy forms a globe. In a dendrimer, the branches are interlinked polymerized chains of molecules, each of which generates new chains, all of which converge to a single focal point or core .
In 1978, Fritz Vogtle and co-workers, introduced dendrimer chemistry and in 1985, Donald A. Tomalia, synthesized the first family of dendrimers. Dendrimers are repeatedly branched roughly spherical large molecules and possess well defined chemical structures. The word dendrimer comes from a Greek word which means to “tree”. At the same time, Newkome’s group independently reported synthesis of similar macromolecules. They called them arborols from the Latin word ‘arbor’ also meaning a tree.The other synonyms for dendrimer include cascade molecules. It is a highly branched synthetic polymer and consists of a monomer unit attached core, where a, leading to a monodisperse, treelike, star-shaped or generational structure with precise molecular weights, diameters in the 2 to 10 nm range size, its unique architectural design, high degree of branching, multivalency, globular structure and representative of a new segment of polymer science, often been referred to as the “Polymers of the 21st century”. Poor solubility, bioavailability, permeability, biocompatibility and toxicity can be overcome by dendrimers. Recent successes in simplifying and optimizing the synthesis of dendrimers provide a large variety of structures with reduced cost of their production. Dendritic polymers or dendrimers provide a route to create very well-defined nanostructures suitable for drug solubilisation applications, delivery of oligonucletide, targeting drug at specific receptor site, and ability to act as carrier for the development of drug delivery system. Dendrimers are being considered as additives in several routes of administration, including intravenous, oral, transdermal, pulmonary and ocular.
STRUCTURE OF DENDRIMERS
A dendrimer is typically symmetric around the core , and often develops a three dimensional morphology .In the view of polymer chemistry dendrimeres are perfect monodisperse macro molecules with regular highly branched three dimensional structures and consist of three architectural components like core,branches and end groups.[7,8]Dendrimers of lower generations (0, 1, and 2) have highly asymmetric shape and possess more open structures as compared to higher generation dendrimers. As the chains growing from the core molecule become longer and more branched (in 4 and higher generations) dendrimers adopt a globular structure. Dendrimers become densely packed as they extend out to the periphery, which forms a closed membrane-like structure. When a critical branched state is reached dendrimers cannot grow because of a lack of space. This is called the ‘starburst effect. For PAMAM dendrimer synthesis it is observed after tenth generation. The rate of reaction drops suddenly and further reactions of the end groups cannot occur. The tenth generation PAMAM contains 6141 monomer units and has a diameter of about 124 Å The increasing branch density withgeneration is also believed to have striking effects on the structure of dendrimers. They are characterised by the presence of internal cavities and by a large number of reactive end groups . Dendritic copolymers are a specific group of dendrimers. There are two different types of copolymer
Segment-block dendrimers are built with dendritic segments ofdifferent constitution. They are obtainedby attaching different wedges to onepolyfunctional core molecule.
Layer-block dendrimers consist of concentric spheres of differing chemistry.They are the result of placing concentric layers around the central core. Hawker and Fréchet synthesised a segment- block dendrimer which had one ether-linked segment and two ester-linked segments. They also synthesised a layer-block dendrimer. The inner two generations were ester-linked and the outer three etherlinked. The multi-step synthesis of large quantities of higher generation dendrimers requires a great effort. This was the reason why Zimmerman’s group applied the concept of self-assembly to dendrimer Synthesis. They prepared a wedgelike molecule with adendritic tail in such a manner that six wedge-shaped subunits could self-assemble to form a cylindrical aggregate. This hexameric aggregate is about 9 nm in diameter and 2 nm thick. It has a large cavity in the centre. The six wedges are held together by hydrogen bonds between carboxylic acid groups and stabilised by Vander Waals interactions. However, the stability of the hexamer is affected by many factors. The aggregate starts to break up into monomers when the solution is diluted, when the aggregate is placed in a polar solvent like tetrahydrofuran (THF), and when the temperature is high. The hexamer’s limited stability is due to its noncovalent nature.
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