DENDRIMERS - A NANOPARTICULATE DRUG CARRIER

DENDRIMERS - A NANOPARTICULATE DRUG CARRIER

Dr. Basu Venkateswara Reddy (1*), Prof. Satyanand Tyagi (2) (1) Department

(V), Hayathnagar,

of

Pharmaceutics, Ranga

Reddy,

St

Pauls

Andhra

College Pradesh,

of

Pharmacy, India-501510;

Turkayamjal Member,

Manuscript Reviewer, Editorial Board Member & Associate Editor, Tyagi Pharmacy Association (TPA), Chattarpur, New Delhi, India-110074. (2) Founder, President, CEO & Manuscript Reviewer, Tyagi Pharmacy Association (TPA) &

Scientific Writer (Pharmacy), Chattarpur, New Delhi, India-110074.

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Abstract Dendrimers are a new class of polymeric materials. They are hyperbranched macromolecules having tree like structure, consisting of a core molecule and alternating layers of monomers. They can be synthesized by divergent and convergent growth methods. The bioactive agents can be easily encapsulated into the dendrimers or chemically attached that is conjugated or physically adsorbed onto the dendrimer surface, serving the desired properties of the carrier to the specific needs of the active material and its therapeutic applications. The design of dendrimers clearly distinguishes these as unique and optimum nanocarriers in medical applications such as drug delivery, gene transfection, tumor therapy and diagnostics etc. Structural advantages allow dendrimers to play an important role in the fields of nanotechnology, pharmaceutical and medicinal chemistry. As a result of their unique behavior, dendrimers are suitable for a wide range of biomedical and industrial applications.

Key Words Dendrimers, nanocarriers, nanotechnology.

Description The word “dendrimer” originated from two words, the Greek word dendron, meaning tree, and meros, meaning part. Dendrimers are characterized by its highly branched 3D structure.

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Dendrimers are mono-dispersed polymers which fall under the broad heading of nanotechnology, which covers the manipulation of matter in the size range of 1-100 nanometers (one million nanometers equal one millimeter) to create compounds, structures and devices with novel, pre-determined properties. Dendrimers are built from a starting atom, such as nitrogen, to which carbon and other elements are added by a repeating series of chemical reactions that produces a spherical branching structure. Dendrimers are constructed by the successive addition of layers to the branching groups. The synthesis of dendrimers involves a core molecule with branching groups to which other branching molecules are added in layers. Each new layer is called a generation. The final generation can incorporate additional active groups that give the particular functionality to the dendrimer. Dendrimers possess three distinguished architectural components, namely 1. An initiator core 2. Interior layers (generations) composed of repeating units, radically attached to the interior core. 3. Exterior (terminal functionality) attached to the outermost interior generations. Dendrimers have a high degree of molecular uniformity, narrow molecular weight distribution, specific size and shape characteristics, and a highly- functionalized terminal surface. It mainly acts as carrier in solubilization applications, delivery of DNA and oligonucletide, targeting drug at specific receptor site. Dendrimers are being considered as additives in several routes of administration, including intravenous, oral, transdermal, pulmonary and ocular. An increasingly large number of drugs being developed today facing problems of poor solubility, bioavailability and permeability, biocompatibility and toxicity dendrimers can work as a useful tool for optimizing drug delivery of such problematic drugs with reduced cost of its production. Also the problem of biocompatibility and toxicity can be overcome by careful surface engineering.

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Recent successes in simplifying and optimizing the synthesis of dendrimers provide a large variety of structures with reduced cost of their production. Also as research progresses, newer applications of dendrimers will emerge and the future should witness an increasing numbers of commercialized dendrimer based drug delivery systems.

Types of Dendrimers: 1. Radially layered poly (amidoamineorganosilicon) dendrimers (PAMAMOS) Consist of hydrophilic, nucleophilic polyamidoamine (PAMAM) interiors and hydrophobic organosilicon (OS) exteriors. Has the ability to complex and encapsulate various guest species offer unprecedented potentials for new applications in nanolithography, lectronics, photonics, chemical catalysis etc. and useful precursors for the preparation of honeycomb like networks with nanoscopic PAMAM and OS domains.

2. Poly (amidoamine) dendrimers (PAMAM) Synthesized by the divergent method, starting from initiator core reagents like ammonia or ethylenediamine. They are commercially available as methanol solutions and ingeneration G 0-10 with 5 different core type and 10 functional surface groups.

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3. Poly (Propylene Imine) dendrimers (PPI) Poly (Propylene Imine) dendrimers (PPI) generally having poly-alkyl amines as end groups, and numerous tertiary trispropylene amines present in the interior portion. It has wide applications in material science as well as in biology. PPI dendrimers are available as AstramolTM.

4. Chiral dendrimers The chirality in these dendrimers is based upon the construction of constitutionally different but chemically similar branches to chiral core. They are potentially used as chiral hosts for enantiomeric resolutions and as chiral catalysts for asymmetric synthesis.

5. Liquid crystalline dendrimers A highly-branched oligomer or polymer of dendritic structure containing mesogenic groups that displays mesophase behavior. They consist of mesogenic (liq. crystalline) monomers.

6. Tecto dendrimer Tecto Dendrimer are composed of a core dendrimer, perform varied functions ranging from diseased cell recognition, diagnosis of disease state drug delivery, reporting location to reporting outcomes of therapy.

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7. Hybrid dendrimers Hybrid dendrimers are hybrids (block or graft polymers) of dendritic and linear polymers obtained by complete mono functionalization of the peripheral amines of a "zero-generation" polyethylenemine dendrimer, provide structurally diverse lamellar, columnar, and cubic self organized lattices that are less readily available from other modified dendritic structures.

8. Multilingual Dendrimers Multilingual Dendrimers contains multiple copies of a particular functional group on the surface.

9. Micellar Dendrimers Micellar dendrimers are unimolecular water soluble hyper branched polyphenylenes micelles.

Applications of dendrimers: Dendrimer possess its unique structural features like nanoscopic size, spheroidal surface, high branching, cavernous interior, etc. and exciting properties, like low viscosity, high solubility, high reactivity, in combination with the high functionalities of the dendritic polymers suggested that they have wide number of potential applications in different fields. Pharmaceutical applications include ocular drug delivery, pulmonary drug delivery, transdermal drug delivery, oral drug delivery, targeted drug delivery, gene delivery, solubility enhancer, cellular delivery of drugs.

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Therapeutic applications include photodynamic therapy, boron neutron capture therapy. Diagnostic applications such as molecular probes, X-ray contrast agents, and MRI contrast agents.

Conclusion The dendrimers holds a promising future in various pharmaceutical applications and diagnostic field in the coming years as they possess unique properties, such as high degree of branching, multivalency, globular architecture and well-defined molecular weight, thereby offering new scaffolds for drug delivery. Recent successes in simplifying and optimizing the synthesis of dendrimers provide a large variety of structures with reduced cost of their production. The chemical modification of the dendritic polymers resulted in a wide range of variation in properties, hence their application. Dendrimers can work as a useful tool for optimizing drug delivery of such problematic drugs. Also the problem of biocompatibility and toxicity can be overcome by careful surface engineering. The bioactive agents may either be encapsulated into the dendrimers or they may be chemically attached or physically adsorbed onto the dendrimer

surface, with

the option to tailor the properties of the carrier to the specific needs of the active material and its therapeutic applications. The biomedical applications of dendrimers clearly illustrate the potential of this new fourth architectural class of polymers and substantiate the high optimism for the future of dendrimers in this important field.

References 1. Barbara Klajnert and Maria Bryszewska. Dendrimers: properties and applications. Acta biochimica polonica 2001; 48(1): 199-208.

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2. H. N. Patel and DR. P. M. Patel. Dendrimer applications- A review. Int J Pharm Bio Sci 2013; 4(2): 454 – 463. 3. Varun trivedi, Upendra Patel. Bhavin Bhimani, Dhirani Daslaniya, Ghanshyam patel, Bijal Vyas. Dendrimer: Polymer of 21st century. IJPRBS 2012; 1(2): 1-21. 4. Mihir Doshi. Dendrimer and its applications. International Journal of Pharmaceutical Sciences Review and Research 2011; 7(2): 104-111. 5. Reshma V.Tambe, Satyabhama S.Pakhare, Manisha G. Jadhav, Shradha S.Tiwari, Chaitrali R. Rai. Dendrimer: A soft polymer. IJRRPAS, 2(3): 513-528.

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