Fabrication and Design of Dendrimers for Cancer Chemotherapy
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Abstract
Since the discovery of dendrimers in 1978, it has received serious attention as a drug carrier polymer most especially in cancer chemotherapeutics where precision and targeted delivery of drug to tumor cells is most desirable. Dendrimers are mostly synthetic, hyper-branched, tree-like globular, nano-sized polymers with excellent physicochemical properties that can be utilized in the formulation, design and delivery of drugs, vaccine and genes to specific receptors in the body. This review focused on the synthesis, types and applications of dendrimers in the delivery of cytotoxic drugs. The review shows that in the last decade, dendrimers have proved to be promising nanocarriers for various drugs including anti-inflammatory, antimicrobial, and anticancer drugs. The application of dendrimers as scaffolds of prodrugs is particularly interesting. Dendrimers are relatively more stable compared with other nano drug carriers and are suitable in formulating drugs for different routes of administration. As more and newer dendrimers are introduced into the market, they will have increasing role in therapeutic delivery of drugs, vaccines and gene.
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References
Barbara, K. and Maria, B. (2001). Dendrimers: properties and application. Acta Biochimica Polonica, 48: 199–208.
Bhadra, D., Bhadra, S., Jain, S. and Jain, N. K. (2003). A PEGylated dendritic nanoparticulate carrier of fluorouracil. Int J Pharm, 257:111-124.
Bhadra, D., Yadav, A.K.., Bhadra, S. and Jain, N.K. (2005). Glycodendrimeric nanoparticulate carriers of primaquine phosphate for liver targeting. Int J Pharm., 295:221–233.
Blume, G. and Cevc, G. (1990). Liposomes for the sustained drug release in-vivo. Biochim Biophys Acta. 1029:91–97.
Brigger, I., Dubernet, C. and Couvreur, P. (2002). Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev. 54:631–651.
Dutta, T., Aghase, H.B., Vijayarajkumar, P., Joshi, M. and Jain, N.K. (2006). Dendrosome-based gene delivery.Journal of Experimental Nanoscience,
:235–248.
Gurdag, S., Khandare, J., Stapels, S., Matherly, L.H. (2006). Activity of dendrimer-methotrexate conjugates on methotrexate sensitive and
resistant cell lines. Bioconjug Chem. 17:275–283.
Fre ́chet, J.M.J. and Tomalia, D.A. (2001), Dendrimers and Other Dendritic Polymers, Wiley, West Sussex, UK. pp 225- 275.
Gupta, U., Dwivedi, S.K., Bid, H.K., Konwar, R. and Jain, N.K. (2010). Ligand anchored dendrimers based nanoconstructs for effective targeting
to cancer Cells. Int J Pharm, 393: 185 – 196.
Hawker, C.J. and Frechet, J.M.J. (1990). Preparation of polymers with controlled molecular architecture: A new convergent approach to dendritic
macromolecules. J Am Chem Soc 112:7638–7647.
Hawker, C.J. (2006). Dendrimers: Novel polymeric nanoarchitectures for solubility enhancement. Biomacromolecules, 7: 649-658.
Ihre, H.R., De Jesus, O.L.P., Szoka, F.C. and Frechet, J.M.J. (2002). Polyester dendritic systems for drug delivery applications: design, synthesis, and
characterization, Bioconjug. Chem. 13:443– 452.
Jain, K. (2005). Nanotechnology based drug delivery for cancer. Technology in Cancer Research & Treatment 4:407.
Kaminskas, L.M., McLeod, V.M., Kelly, B.D. and Sberna, G. (2012). A comparison of changes to doxorubicin pharmacokinetics, antitumor activity,
and toxicity mediated by PEGylated dendrimer and PEGylated liposome drug delivery systems. Nanomedicine,8:103–111
Kim, Y.K. and Zimmerman, S.C. (1998). Applications of dendrimers in bioorganic chemistry. Curr Opin Chem Biol 2:733–742.
Kim, Y.K. and Zimmerman, S.C. (1998). Applications of dendrimers in bioorganic chemistry. Curr Opin Chem Biol 2:733–742.
Kipp, J. (2004). The role of solid nanoparticle technology in the parenteral delivery of poorly water soluble drugs. International Journal of
Pharmaceutics, 284:109-122.
Klibanov, A.L., Maruyama, K., Torchilin, V.P. and Huang, L. (1990). Amphiphathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 268:235–237.
Krishna, R. and Mayer, L.D. (2000). Multidrug resistance (MDR) in cancer: Mechanisms, reversal using modulators of MDR and the role of
MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur J Pharm Sci. 11:265–283.
Kesharwani, P., Keerti, J. and Narendra K. J. (2014). Dendrimer as nanocarrier for drug delivery. Progress in Polymer Science 39: 268– 307.
Kukowska-Latallo, J. F., Bielinska, A. U., Johnson, J., Spindler, R., Tomalia, D. A. and Baker, J. R. (1996). Efficient transfer of genetic material into
mammalian cells by using Starburst. polyamidoamine dendrimers. Proc. Natl. Acad. Sci. 93:4897– 4902.
Kojima, C., Kono, K., Maruyama, K. and Takagishi, T. (2000). Synthesis of polyamidoamine dendrimers having poly (ethylene glycol) grafts and their ability to encapsulate anticancer drugs. Bioconj Chem. 11:910–917.
Kono, K.., Liu, M. and Fréchet, J.M. (1999). Design of dendritic macromolecules containing folate or methotrexate residues. Bioconjugate Chemistry, 10:1115–1121.
Kihara, F., Arima, H., Tsutsumi, T., Hirayama, F. and Uekama, K. (2003). In-vitro and in-vivo gene transfer by an optimized alpha cyclodextrin conjugate with polyamidoamine dendrimer. Bioconjug Chem 14: 342–350.
Langer, R. (1990). New methods of drug delivery. Science, 249:1527– 1533.
Liu, M. Kono, K. and Frechet, J.M. (2000). Water-soluble dendritic unimolecular micelles: their potential as drug delivery agents. J. Control. Release, 65: 121– 131.
Links, M. and Brown, R. (1999). Clinical relevance of the molecular mechanisms of resistance to anti- cancer drugs. Expert Rev Mol Med. 199:1–21.
Martin, J., Roeck, J. and Ryder, P. (1985). A new class of polymers: Starburst® dendritic macromolecules. Polym. J. 17: 117– 132.
Malik ,N., Evagorou, E.G. and Duncan, R. (1999). Dendrimer platinate: A novel approach to cancer chemotherapy. Anticancer Drugs, 10:767–776.
Myc, A., Majoros, I. J., Thomas, T. P. and Baker, J. R. (2007). Dendrimer-based targeted delivery of an apoptoticsensor in cancer cells.
Biomacromolecules, 8: 13–18.
Mintzer, M. A. and Grinstaff, M. W. (2011). Biomedical applications of dendrimers. Chem Soc Rev., 40:173–190.
Maeda, H., Wu, J., Sawa,T., Matsumura,Y. and Hori, K (2000). Tumor vascular permeability and the EPR effect in macromolecular therapeutics. J.
Control. Release, 65: 271– 284.
Newkome, G.R. Moorefield, C.N. and Vogtle, F. (2001). Dendrimers and Dendrons: Concepts, Syntheses, Applications, Wiley-VCH, Weinheim, Germany.
Ooya, T., Lee, J. and Park, K. (2004). Hydrotropic dendrimers of generations four and five: Synthesis, characterization, and hydrotropic
solubilization of paclitaxel. Bioconjug Chem., 15: 1221–1229.
Ould-Ouali, L., Noppe, M., Langlois, X., Willems, B., and Te Riele, P. (2005). Self assembling PEG copolymers for oral delivery of poorly water soluble drugs: A case study with risperidone. Journal of Controlled Release, 102:657‐668.
Padilla De Jesus, O.L., Ihre, H.R., Gagne, L., Frechet, J.M. and Szoka, F.C. (2002). Polyester dendritic systems for drug delivery applications: in-vitro and in-vivo evaluation. Bioconjug. Chem. 13: 453– 461.
Patri, A.K., Kukowska-Latallo, J.F. and Baker, J.R. (2005). Targeted drug delivery with dendrimers: Comparison of the release kinetics of covalently
conjugated drug and non-covalent drug inclusion complex. Adv. Drug Delivery Rev. 57:2203– 2214.
Pushkar, S., Philip, A., Pathak, K. and Pathak, D. (2006). Dendrimers:Nanotechnology Derived Novel Polymers in Drug Delivery. Indian J. Pharm. Educ. Res.,40: 153-158.
Quintana, A., Raczka, E., Piehler, L., Lee, I., Myc, A., Majoros, I., Patri, A..K., Thomas, T., Mule, J. and Baker, J.R. (2002). Design and function of a
dendrimer based therapeutic nanodevice targeted to tumor cells through the folate receptor. Pharm Res, 19:1310- 1316.
Rajesh babu, V., Mallikarjun, V., Nikhat, S.R. and Srikanth, G. (2010). Dendrimers: A new carrier system for Drug Delivery. Int J Pharm and App Sci.
:1-10.
Richter-Egger, D.L., Tesfai, A. and Tucker, S.A. (2001). Spectroscopic Investigation of poly(propyleneimine) dendrimers. Anal. Chem. 73:5743-5751.
Saktivel, T., Toth, I. and Florence, A.T. (1998). Synthesis and physicochemical properties of lipophillic polyamide dendrimers. Pharm. res., 15: 776-782.
Sideratou, Z., Kontoyianni, C., Drossopoulou, G.I. and Paleos, C.M. (2010). Synthesis of a folate functionalized PEGylated poly (propylene imine)
dendrimer as prospective targeted drug delivery system. Bioorg. Med. Chem. Lett., 20: 6513–6517.
Surendra T., Lipika B., and Malay, D. K. (2014). Dendrimer chemistry and host guest interactions for drug targeting. Int J Pharm Sci and Res, 5(1): 2320-2514.
Tack, F., Bakker, A,, Maes, S., Dekeyser, N. and Bruining, M. (2006). Modified poly(propylene imine) dendrimers as effective transfection agents for catalytic DNA enzymes (DNAzymes). J Drug Target, 14:69–86.
Twyman, L.J., Beezer, A.E., Esfand, R., Hardy, M.J. and Mitchell, J.C. (1999). The synthesis of water soluble dendrimers, and their application as
possible drug delivery systems. Tetrahedron Lett. 40: 1743– 1746.
Tomalia, D.A., Baker, V., Dewald,-Hall, V.G. and Kallos, S. (2005). Birth of a new macromolecular architecture: Dendrimers as quantized building
blocks for nanoscale synthetic polymer chemistry. Prog Polym Sci, 30:294–324.
Tripathi ,P.K., Khopade, A.J., Nagaich, S., Shrivastava, S., Jain, S., and Jain, N.K. (2002). Dendrimer grafts for delivery of 5-fluorouracil. Pharmazie,
:261-264.
Wada, K., Arima, H., Tsutsumi, T., Chihara, Y., Hattori, K., and Uekama, K. (2005). Improvement of gene delivery mediated by mannosylated
dendrimer/alpha cyclodextrin conjugates. J Control Release, 104:397–413.
Wang, Y., Guo, R., Cao, X., Shen, M., andShi, X. (2011). Encapsulated of 2-methoxyestradiol within multifunctional poly (amidoamine) dendrimers for targeted cancer therapy. Biomaterials, 32:3322–3329.
Wolinsky, J. B. and Grinstaff, M.W. (2008). Therapeutic and diagnostic applications of dendrimers for cancer treatment. Adv. Drug Deliv. Rev., 60:
–1055.
Yiyun, C., Zhenhua, X., Minglu, M and Tonguen, X. (2008). Dendrimers as Drug Carriers: Applications in Different Routes of Drug. J. Pharma. Sci., 97: 123-143.
Zhou, Z., D’Emanuele, A. and Attwood, D. (2013). Solubility enhancement of paclitaxel using a linear-dendritic block copolymer. Int J Pharm., 452:173–179.