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Dendrimers: The emerging pharmaceutical tool from nanoscale science

Kamal Dua, VK Sharma, Kavita PabrejaWednesday, December 3, 2008, 08:00 Hrs  [IST]

The dendrimer structures represent a new class of macromolecular architecture and precise construction modules in the emerging area of nano-scale science and technology. The rapidly accelerating research and development activities in dendrimers and dendritic materials provide critically needed nanoscale building blocks suitable for the development of high performance materials. Dendrimers are widely recognized as the most versatile, compositionally and structurally controlled nanoscale building blocks available. The name comes from the Greek "δενδρον"/ dendron, meaning "tree". Synonymous terms are arborols and cascade-molecules. Dendrimer is an internationally accepted term. Dendrimers and dendrons are repeatedly branched, monodisperse, and usually highly symmetric compounds. There is no apparent difference in defining dendrimer and dendron. A dendron usually contains a single chemically addressable group that is called the focal point. Because of the lack of the molar mass distribution high-molar-mass dendrimers and dendrons are macromolecules but not polymers. The dendrimers are repeatedly branched molecules. The huge number of papers on dendritic architectures such as dendrimers, dendronized, hyperbranched and brush-polymers has generated a vast variety of inconsistent terms and definitions making a clear and concise unfolding of this topic highly difficult. The first dendrimers were synthesized divergently by Vögtle in 1978, by Denkewalter and his coworkers at Allied Corporation as polylysine dendrimers in 1981, by Tomalia at Dow Chemical in 1983 and in 1985, and by Newkome in 1985. In 1990 a convergent synthesis was introduced by Mingjun Liu. The dendrimers then experienced an explosion of scientific interest because of their unique molecular architecture. This resulted in over 5,000 scientific papers and patents published by the end of 2005. Salient features leading to uniqueness The dendritic molecules are repeatedly branched species that are characterized by their structure perfection. The latter is based on the evaluation of both symmetry and polydispersity. The area of dendritic molecules can roughly be divided into the low-molecular weight and the high-molecular weight species. The first category includes dendrimers and dendrons whereas the second encompasses dendronized polymers, hyperbranched polymers, and brush-polymers (also called bottle-brushes). The properties of dendrimers are dominated by the functional group on the molecular surface. Dendritic encapsulation of functional molecules allows for the isolation of the active site, a structure that mimics the structure of active sites in biomaterials because dendritic scaffolds separate internal and external functions. For example, a dendrimer can be water-soluble when its end group is a hydrophilic group, like a carboxyl group. It is theoretically possible to design a water-soluble dendrimer with internal hydrophobicity, which would allow it to carry a hydrophobic drug in its interior. Recently, it has been shown that redox-active nanoparticles can be synthesized, placing the redox molecules between the nanoparticle core and the dendritic wedges; despite their isolation, some of the redox molecules (COOH in this case) remained uncoupled, and thus still reactive. Another property is that the volume of a dendrimer increases when it has a positive charge. If this property can be applied, dendrimers can be used for drug delivery systems (DDS) that can give medication to the affected part inside a patient's body directly. The dendrimers are nanostructures that can be precisely designed and manufactured for a wide variety of applications. Dendrimers are the first large, man-made molecules with precise, nano-sized composition and well-defined three-dimensional shapes. Current polymer molecules are long, spaghetti-like strands that grow in only two directions. Dendrimer molecules grow three-dimensionally by the addition of shells of branched molecules to a central core. The cores are also spacious and have "sticky" points on the outside to which various chemical units can be attached. By adjusting chemical properties of the core, the shells, and especially the surface layer, dendrimers can be tailored to fit the needs of specific applications. Versatile applicability The dendrimer-based technologies provide exciting new interfaces between chemistry, biology and advanced materials. Dendrimers have the ability to act as appropriate containers for delivery vehicles in-vitro and in-vivo due to their specific, precise and predictable custom designed dendritic polymer architectures. As an enabling technology, dendrimers provide the vehicle for targeting and delivery mechanisms for a vast array of diagnostic and therapeutic products. Their precise and designable architecture, tuneable solubility, low toxicity and immunogenicity, and bioattachment capability make dendrimers the ideal building blocks for biotechnology. Because of their precise architecture and construction, dendrimers possess inherently valuable physical, chemical and biological properties. These properties include: " Efficient membrane transport - Dendrimers have demonstrated rapid transport capabilities across biological membranes. " High loading capacity - Dendrimer structures can be used to carry and store a wide range of metals, organic or inorganic molecules by encapsulation and absorption. " High uniformity and purity - The synthetic process used produces dendrimers with uniform sizes, precisely defined surface functionality, and very low impurity levels. " Low toxicity - Most of the dendrimer systems display very low cytotoxicity levels. " Low immunogenicity - Dendrimers commonly manifest a very low or negligible immunogenic response when injected or used topically. ( The authors are with D. J. College of Pharmacy, Niwari Road, Modinagar-201 204, Uttar Pradesh)

 
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