Dendrimer a versatile polymer in drug delivery

Shakti K Singh, G K Lohiya, P P Limburkar, N B Dharbale, V K Mourya

Abstract


Dendrimers are a unique class of synthetic macromolecules having highly branched, three-dimensional, nanoscale architecture with very low polydispersity and high functionality. Structural advantages allow dendrimers to play an important role in the fields of nanotechnology, pharmaceutical and medicinal chemistry. This review discusses several aspects of dendrimers, including preparation, dendrimer-drug coupling chemistry, structural models of dendrimer-based drug delivery systems, and physicochemical and toxicological properties. Dendrimers have emerged as one of the most interesting themes for researchers as a result of their unique architecture and macromolecular characteristics. Several groups are involved in exploring their potential as versatile carriers in drug delivery. The use of dendrimers in drug delivery has
been reviewed extensively. The increasing relevance of the potential of dendrimers in drug delivery emphasizes the need to explore the routes by which they can be administered. The high level of control possible over the architectural design ofdendrimers; their size, shape, branching length/density, and their surface functionality clearly distinguish 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. This review clearly demonstrates the potential of this new fourth major class of polymer architecture and indeed substantiates the high hopes for the future of dendrimers.


Full Text:

PDF

References


Gupta U, Agashe HB, Jain NK. Polypropylene Imine: Dendrimer

Mediated Solubility Enhancement: Effect of pH and Functional Groups

of Hydrophobes. J Pharm Pharmaceut Sci 2007;10:358-67.

Devarakonda B, Hill RA, Liebenberg W, Brits M, De Villiers MM.

Comparison of aqueous solubilization of practically insoluble

niclosamide by polyamidoamine (PAMAM) dendrimers and cyclodextrins.

Int J Pharm 2005;300:193-209.

Devarakonda B, Li N, De Villiers M. Effect of Polyamidoamine (PAMAM)

Dendrimers on the in vitro release of water-insoluble nifedipine from

aqueous gels. AAPS PharmSciTech 2005;6:504-12.

Liu M, Kono K, Frechet JM. Water-soluble dendritic unimolecular

micelles: Their potential as drug delivery agents. J Control Release

;65:121-31.

D`Emanuele A, Jevprasesphant JP, Penny J, Attwood D. The use of

a dendrimer propranolol prodrug to bypass efflux transporters and

enhance oral bioavailability. J Control Release 2004;95:447-53.

Milhem OM, Myles C, McKeown NB, D’Emanuele A. Polyamidoamine

Starburst dendrimers as solubility enhancers. Int J Pharm

;197:239‐41.

Beezer AE, King AS, Martin IK, Mitchel JC, Twyman LJ, Wain CF.

Dendrimers as potential drug carriers;encapsulation of acidic

hydrophobes within water soluble PAMAM derivatives. Tetrahedron

;59:3873-80.

Khopade AJ, Caruso F, Tripathi P, Nagaich S, Jain NK. Effect of dendrimer

on entrapment and release of bioactive from liposomes. Int J Pharm

;232:157-62.

Chauhan AS, Sridevi S, Chalasani KB, Jain AK, Jain SK, Jain NK, et al.

Dendrimer-mediated transdermal delivery: Enhanced bioavailability

of indomethacin. J Cont Rel 2003;90:335-43.

Asthana A, Chauhan AS, Diwan PV, Jain NK. Poly (amidoamine) (PAMAM) Dendritic Nanostructures for Controlled Site-specific Delivery of Acidic Anti-Inflammatory Active Ingredient. AAPS PharmSciTech 2005;13:200-8.

Bhadra D, Bhadra S, Jain S, Jain NK. A PEGylated dendritic nanoparticulate carrier of fluorouracil. Int J Pharm 2003;257:111-24.

Tomalia DA. Dendritic macromolecules: Synthesis of starburst

dendrimers. Macromolecules 1986;19:2466-7.

Kim C. Advanced pharmaceutics: Physicochemical principles. New York:CRC Press;p. 409-12.

Esfand R, Tomalia DA. Poly (amidoamine) (PAMAM) dendrimers: From

biomimicry to drug delivery and biomedical applications. Drug Discov

Today 2001;6:427-36.

Chauhan AS, Jain NK, Diwan PS, Khopade AS. Solubility enhancement

of indimethacin with PAMAM dendrimer and targeting to inflammatory

regions of arthritic rats. J Drug Targeting 2004;12:575-83.

Tomalia DA. Birth of a new macromolecular architecture: Dendrimers as quantized building blocks for nanoscale synthetic polymer chemistry.

Prog Polym Sci 2005;30:294-324.

Jain NK. Advances in controlled and novel drug delivery: Delhi: CBS

Publishers and Distributors;2000. p. 361-70.

Available from: http://www.dnanotech.com. [last accessed January

.

Available from: http://www.pubmed.com. [last accessed March 2000].

Available from: http://www.uspto.gov. [last accessed September 2005].

Rutt SJ, Maebus SB. 3rd annual BBC conference on nano/bio convergence.

Cambridge;Foley and Lardner LLP;2004. p. 1-5.

Pushkar S, Philip A, and Pathak K. Dendrimers: Nanotechnology derived novel polymers in drug delivery. Ind J Pharm Edu Res 2006;40:153-7.

Barbara K, Maria B. Dendrimers: Properties and application. Acta

Biochemica Polinica 2001;48:199-208.

Newkome GR. Dendrimers and dendrons: Concept, Synthesis,

Applications. New York: Wiley- VCH;2001. p. 44, 51, 68, 61

Tomalia DA, Svenson S. Dendritic macromolecules: Synthesis of

starburst dendrimers. Macromolecules 1986;19:2466-7.

Peterson J, Ebber A, Veiko A. Synthesis and CZE analysis of PAMAM

dendrimers with an ethylenediamine core. Proc Estonian Acad Sci

Chem 2001;50:156-66.

Denkewalter RG. Macromolecular highly branched diaminocarboxylic

acids. Chem Abstr 1984;100:103907.

Bezouska K. Design, functional evaluation and biomedical applications

of carbohydrate dendrimers (glycodendrimers). J Biotechnol

;90:269-90.

Grinstaff MW. Biodendrimers: New polymeric biomaterials for tissue

engineering. Chemistry 2002;8:2839-46.

Bhadra S, Bhadra D, Jain NK. PEGylated Dendritic nanoparticulate carrier

of fluorouracil. Int J Pharm 2003;257:111-24.

Istvan JM, Scott W, Baker JR. Acetylation of Poly (amidoamine)

Dendrimers. Macromolecules 2003;36:5526-9.

Uekama K, Chihara, Y, Koki, W, Enhancement of gene transfer activity

mediated by mannosylated dendrimer/alpha cyclodextrin activity

conjugate. J Control Release 2006;116:64-74.

Jevprasesphant R, Penny F, Attwood D, McKeown NB. Engineering of

dendrimer surfaces to enhance transepithelial transport and reduce

cytotoxicity. Pharma Res 2003;20:1543-50.

Svenson S, Tomalia DA. Dendrimer Biomedical applications reflection

on field. Adv Drug Del Rev 2005;57:2106-29.

Duncan R, Izzo L. Dendrimer biocompatibility and toxicity. Adv Drug

Del Rev 2005;57:2215-37.

Frechet JM, Tomalia DA. Dendrimers and other dendritic polymers,

Wiley series in polymer science. John Wiley and Sons. 2004. p. 256-60.

Achar S. Organoplatinum dendrimers formed by oxidative addition.

Angew Chem Int Ed Engl 1994;33:847-9.

Liu Z, Michael A. FT-IRAS spectroscopic studies of the interaction of

avidin with biotynylated dendrimer surfaces. Colloids and surfaces.

Biointerfaces 2004;35:197-203.

Miller TM, Kwock EW, Neenan TX. Synthesis of four generations of

monodisperse aryl ester dendrimers based on 1, 3,5-benzenetricarboxylic

acid. Macromolecules 1992;25:3143-8.

Wilken R, Adams J. End group dynamics of fluorescently labeled

dendrimers. Macromol Rapid Commun 1997;18:659-65.

Hummelen JC, Van JL Dongen, Meijer EW. Electrospray mass

spectrometry of poly (propylene imine) dendrimers-the issue of

dendritic purity or polydispersity. Chem Eur J 1997;3:1489-93.

Rietveld IB, Smit AM. Colligative and viscosity properties of poly

(propylene imine) dendrimers in methanol. Macromolecules

;32:4608-14.

Hofkens J, Verheijen W, Shukla R. Detection of a single dendrimer

macromolecule with a fluorescent dihydropyrrolopyrroledione (DPP)

core embedded in a thin polystyrene polymer film. Macromolecules

;31:4493-7.

Zeng F. Supramolecular polymer chemistry: Design Synthesis,

characterization and kinetics, thermodynamics, and fidelity of

formation of self assembeled dendrimers. Tetrahedron 2002;58:825-43.

Bossman AW, Janseen Meijer EW. Five generations of nitroxyl-

functionalized dendrimers, Macromolecules 1997;30:3606-11.

Brothers HM. Slab gel and capillary electrophoresis characterization

of poly amidoamine dendrimers. J Chromatogram 1998;A814:233-46.

Shi X, Patri AK, Lesniak W, Islam MT, Zhang C, Baker JR Jr, et al.

Analysis of poly (amidoamine) succinamic acid dendrimers by slab-gel

electrophoresis and capillary sone electrophoresis. Electrophoresis

;26:2960-7.

Caminade AM. Characterization of dendrimers, Adv Drug Deliv Rev

;57:2130-46.

Yang H, Kao WJ. Dendrimers for pharmaceutical and biomedical

applications. J Biomater Sci Polymer Edn 2006;17:3-19.

Zhuo RX. In vitro release of 5-fluorouracil with cyclic core dendritic

polymer. J Control Release 1999;57:249-57.

Tansey W, Cao XY, Pasuelo MJ, Wallace S. Synthesis and characterization

of branched poly (l-lutamic acid) as a biodegradable drug carrier.

J Control Release 2004;94:39-51.

Devarakonda B, Hill RA, Villiers MM. The effect of PAMAM dendrimer

generation size and surface functional group on the aqueous solubility

of nifedipine. Int J Pharm 2004;284:133-40.

Chauhan AS, Jain AK, Jain NK. Dendrimer-mediated transdermal

delivery: Enhanced bioavailability of indomethacin. J Control Release

;90:335-43.

Wang ZX, Yoshiaki I, Yoshifumi H. Mechanism of enhancement

of effect of dendrimers on transdermal permeation through

polyhydroxyalkanoate matrix. J Bioscience Bioeng 2003;96:537-40.

Cheng YY, Man N, Xu TW. Transdermal delivery of nonsteroidal anti

inflammatory drugs mediated by PAMAM dendrimers. J Pharm Sci

;96:595-602.

Vandamme TF, Broberck L. PAMAM dendrimers as ophthalmic vehicles

for ocular delivery of pilocarpine nitrate and tropicamide. J Control

Release 2005;102:23-38.

Available from: http://www.starpharma.com.[last accessed December

.

Davis FJ. Polymer Chemistry A practical approach G.R. Oxford: Oxford

University Press;2004. p. 188-98.

Bielinska AU, Chen C, Johnson J, Baker JR. DNA complexing with

polyamidoamine dendrimers: Implications for transfection. Bioconjug

Chem 1999;10:843-50.

Choi JC, Nam K, Park JY. Enhanced transfection efficiency of PAMAM

dendrimers modification with L-arginine. J Control Release 2004;99:445-

Fahlvik, Simon. Ultrafine lightly coated superparamagnetic particles

for MRI .US patent 4606907.

Sheela DK, Michael A, Steven W. Specific targeting of folate-dendrimer

MRI contrast agents to the high affinity folate receptor expressed

in ovarian tumor xenografts. MAGMA 2001;12:104-13.

Svenson S, Tomalia DA. Dendrimer Biomedical applications reflection

on field. Adv Drug Del Rev 2005;57:2106-29.

Chakib H, Rainer H. Hyperbranched polymers as platforms for catalysts.

Top Organomet Chem 2006;20:149-76.

Esumi K, Matsumoto T, Seto Y. Preparation of gold-gold/silver-dendrimer

nanocomposites in the presence of benzoin in ethanol by UV irradiation.

J Colloid Interface Sci 2005;284:199-203.

Istvan JM, Thommey PT, Chandan B. Poly (amidoamine) dendrimer-based

multifunctional engineered nanodevice for cancer therapy. J Med Chem

;48:5892-9.




DOI: http://dx.doi.org/10.22377/ajp.v3i3.263

Refbacks

  • There are currently no refbacks.