Dendrimers: The Novel Pharmaceutical Drug Carriers
DOI:
https://doi.org/10.37285/ijpsn.2009.2.2.1Abstract
Dendrimers represent a novel class of structurally controlled macromolecules derived from a branches-upon-branches structural motif. These consist of well defined, highly branched moieties that radiate from a central core and are synthesized through a stepwise, repetitive reaction sequence that guarantees complete shells for each generation, leading to formation of monodisperse polymers. The synthetic procedures developed for dendrimer preparation permit nearly complete control over the critical molecular design parameters, such as size, shape, surface/interior chemistry, flexibility, and topology by virtue of which these macromolecules offer diverse applications in drug delivery, solubility enhancement, gene therapy and diagnostic field. This article provides an insight into the structure, synthesis, properties, types and the applications of dendrimers in the bio-medical field.
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Keywords:
Dendrimers, Monodisperse polymers, Polyamidoamine (PAMAM) dendrimers, Dendriples, Dendrisome
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Adam G, Neuerbug J, Spuntrup E, and Muhler A. Dynamic contrast- enhanced MR imaging of upper abdomen: enhancement properties of gadolinium-DTPA-polylysine. J. Magn. Reson. 32: 622-628 (1994).
Al-Jamal KT, Ramaswamy C, and Florence AT. Supramolecular structures from dendrons, and dendrimers. Adv. Drug Deliv. Rev. 57: 2238–2270 (2005).
Al-Jamal KT, Sakthivel T, and Florence AT. Dendrisomes: cationic lipidic dendron vesicular assemblies. Int. J. Pharm. 254: 33-36 (2003).
Bai S, Thomas C, and Ahsan F. Dendrimers as a carrier for pulmonary delivery of Enoxaparin, a low molecular weight Heparin. J. Pharm. Sci. 96: 2090-2105 (2006).
Bourne MW, Margerun L, Campion B, and Lai JJ. Evaluation of the effects of gadolinium dendrimer on 3D magnetic resonance angiography of body. J. Magn. Reson. Imaging 6: 305-10 (1996).
Camerano J, Casado M, and Ciriano M. Tris (pyrazolyl) borate carbosilane dendrimers and metallodendrimers. Dalton Trans. 44: 5287–5293 (2006).
Chauhan AS, Sridevi S, Chalasani KB, Jain AK, Jain SK, Jain NK, and Diwan PV. Dendrimer mediated transdermal delivery: Enhanced bioavailability of indomethacin. J. Control. Release 90: 335–343 (2003).
Cheng Y. External electrostatic interaction versus internal encapsulation between cationic dendrimers and negatively charged drugs: which contributes more to solubility enhancement of the drugs? J. Phys. Chem. 112: 8884-90 (2008).
Cheng YY, and Xu TW. Solubility of nicotinic acid in polyamidoamine (PAMAM) dendrimer solutions. Eur. J. Med. Chem. 40: 1384–1389 (2005a).
Cheng YY, Fu RQ, and Xu TW. Polyamidoamine (PAMAM) dendrimers in dye decolorisation. Polym Polym Composites 13: 831–833 (2005c).
Cheng YY, Xu TW, and Fu RQ. Polyamidoamine dendrimers used as solubility enhancers of ketoprofen. Eur. J. Med. Chem. 40: 1390–1393 (2005b).
Cheng YY, Xu TW, and He PS. Polyamidoamine (PAMAM) dendrimers as curing agents: The optimum PAMAM concentration selected by dynamic torsional vibration method and thermogravimetric analysis. J. Appl. Polym. Sci. Symp. 103: 1430–1434 (2007).
Cheng YY, Xu TW, and Li M. Potential of Polyamidoamine dendrimer used as carrier of camphothecin based on encapsulation studies. Eur. J. Med. Chem. 43:1-5 (2007a).
Chun Li. Polymer Conjugates for Cancer Therapy, Poly (-glutamic acid) anti cancer drug conjugates. Adv. Drug Deliv. Rev. 54: 695-713 (2002).
Credi A, Ribera BF, and Venturi M. From supramolecular electrochemistry to molecular-level devices. Electrochem. Acta. 49: 3865–3872 (2004).
Crooks RM, Lemon BI, Sun L, Yeung LK, and Zhao M. Functionalizing the interior of dendrimers: Synthetic challenges and applications. Top. Curr. Chem. 212: 81-135 (2001).
Cuadrado I, Moran M, Casado C, Alonso B, and Losada J. Organometallic dendrimer with transition metals. Coord. Chem. Rev. 193-195: 395-445 (1999).
D'Emanuele A, Jevprasesphant R, Penny J, and Attwood D. The use of a dendrimer-propranolol prodrug to bypass efflux transporters and enhance oral bioavailability. J. Control. Release 95: 447-53 (2004).
Devarakonda B, Li N, and DeVilliers MM. Effect of Polyamidoamine (PAMAM) Dendrimers on the In Vitro Release of Water-Insoluble Nifedipine from Aqueous Gels. AAPS Pharm. Sci.Tech. 6: 504-12 (2005).
Dufes C, Uchegbu IF, and Schatzlein AG. Dendrimers in gene delivery. Adv.Drug Deliv. Rev.57: 2177-2202 (2005).
Dutta T, Agashe H, Garg M, Balakrishnan P, Kabra M, and Jain NK. Poly (propyleneimine) dendrimer based nanocontainers for targeting of efavirenz to human monocytes/macrophages in vitro. J. Drug Target. 15: 89-98 (2007).
Frechet JMJ. Functional polymers and dendrimers: Reactivity, molecular architecture, and interfacial energy. Science 263: 1710–1715 (1994).
Gillies ER, and Frechet JMJ. Dendrimers and dendritic polymers in drug delivery. Drug Discov. Today 10: 35-43 (2005).
Hawker CJ, Wooley KL, and Frechet JMJ. Convergent synthesis of dendrimers. Science 269: 1080 (1995).
Jain NK, Agarwal A, Saraf S, Asthana A, Gupta U, and Gajbhiye V. Ligand based dendritic systems for tumor targeting. Int. J. Pharm. 350: 3-13 (2008).
Kojima C, Kono K, Maruyama K, and Takagishi T. Synthesis of polyamidoamine dendrimers having poly (ethylene glycol) grafts and their ability to encapsulate anticancer drugs. Bioconjug. Chem. 11: 910-917 (2000).
Kolhe P, Misra E, Kannan RM, Kannan S, and Lieh-Lai M. Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers. Int. J. Pharm. 259: 143-60 (2003).
Kumar PV, Agashe H, Dutta T, and Jain NK. PEGylated Dendritic Architecture for Development of a Prolonged Drug Delivery System for an Antitubercular Drug. Curr. Drug Deliv. 4: 11-19 (2007).
Lee JJ, and Ford WT. Reactivity of organic anions promoted by a quaternary ammonium ion dendrimer. Macromolecules 27: 4632-34 (1994).
Ma ML, Cheng YY, Xu ZH, Xu P, Qu HO, Fang YJ, Xu TW, and Wen LP. polyamidoamine (PAMAM) dendrimers as biocompatible carriers of Quinolone antimicrobials. Eur. J. Med. Chem. 42: 1032-38 (2006a).
Ma ML, Cheng YY, Xu ZH, Xu P, Qu HO, Fang YJ, Xu TW, and Wen LP. Evaluation of polyamidoamine (PAMAM) dendrimers as drug carriers of anti-bacterial drugs using sulfamethoxazole (SMZ) as a model drug. Eur. J. Med. Chem. 42: 93–98 (2006b).
Malik N, Evagorou EG, and Duncan R. Dendrimer-platinate: a novel approach to cancer chemotherapy. Anticancer Drugs 10: 767-76 (1999).
Man N, Cheng YY, Xu TW, Ding Y, Li ZW, Huang GY, Shi YY, and Wen LP Dendrimers as potential drug carriers. Part II Prolonged delivery of ketoprofen by in vitro and in vivo studies. Eur. J. Med. Chem. 41: 670-674 (2006).
Meijer EW, Jansen JF, and Brabander VDB. Encapsulation of guest molecules into a dendritic box. Science 266: 1226–1229 (1994).
Milhem OM, Myles C, and McKeown NB. Polyamidoamine starburst dendrimers as solubility enhancers. Int. J. Pharm. 197: 239-41 (2000).
Momotake A, and Arai T. Photochemistry and photophysics of stilbene dendrimers and related polymers. J. Pharm. Sci. 97: 343-48 (2004).
Mourey TH, Turner SR, Rubenstein M, Frechet JMJ, Hawker CJ, and Wooley KL. Unique behaviour of dendritic macromolecules: Intrinsic viscosity of polyether dendrimers. Macromolecules 25: 2401–2406 (1992).
Myc A, Douce TB, Ahuja N, Kotlyar A, Kukowska-Latallo J, Thomas TP, and Baker JR. Preclinical antitumor efficacy evaluation of dendrimer-based methotrexate conjugates. Anticancer Drugs 19: 43-49 (2008).
Neerman MF. The efficiency of a PAMAM dendrimer toward the encapsulation of the antileukemic drug 6-mercaptopurine. AntiCancer Drugs 18: 839-842 (2007).
Patri AK, Majoros IJ, and Baker Jr. Dendritic polymer macromolecular carriers for drug delivery. Curr. Opin. Chem. Biol. 6: 466-71 (2002).
Paul D, Hiroyuki M, Shinoda S, and Tsukube H. Proteo-dendrimers designed for complementary recognition of cytochrome c: dendrimer architecture toward nanoscale protein complexation. Chemistry 12: 1328-38 (2005).
Richter-Egger DL, Tesfai A, and Tucker SA. Spectroscopic investigations of poly(propyleneimine) dendrimers using the solvatochromic probe phenol blue and comparisons to poly (amidoamine) dendrimers. Anal. Chem. 73: 5743-5751 (2001).
Sakthivel T, and Alexander TF. Dendrimers & Dendrons: Facets of Pharmaceutical Nanotechnology, Drug Delivery Tech. 3, Issue 5: (2003).
Sayed-Sweet Y, Hedstrand DM, Spinder R, and Tomalia DA. Hydrophobically modified poly (amidoamine) (PAMAM) dendrimers: Their properties at the air–water interface and use as nanoscopic container molecules. J. Mater. Chem. 7: 1199–1205 (1997).
Shah DS, Sakthivel T, Toth I, Florence AT, and Wilderspin AF. DNA transfection and transfected cell viability using amphipathic asymmetric dendrimers. Int. J. Pharm. 208: 41-48 (2000).
Sigal GB, Mammen M, Dahmann G, and Whitesides GM. Polyacrylamides bearing dependant-sialoside groups strongly inhibit agglutination of erythrocytes by influenza virus: The strong inhibition reflects enhanced binding through cooperative polyvalent interactions. J. Am. Chem. Soc. 118: 3789–3800 (1996).
Tomalia DA, and Frechet JMJ. Discovery of dendrimers and dendritic polymers: a brief historical perspective. J. Polym. Sci. A. 40: 2719-2728 (2002).
Tomalia DA, Baker H, Dewald J, Hall M, Kallos G, Martin S, Ryder J, and Smith P. A new class of polymers: Starbust-dendritic Macromolecules. Polym. J. 17: 117-32 (1985).
Tomalia DA, Naylor AM, and Goddard WA. Starburst dendrimers: molecular-level control of size, shape, surface chemistry, topology, and flexibility from atoms to macroscopic matter. Angew. Chem. Int. 29: 138-48 (1990).
Tomalia DA, Yin R, and Zhu Y. Architectural copolymers: Rod shaped, cylindrical dendrimers. J. Am. Chem. Soc. 120: 2678 (1998).
US Patent (WO/2000/6068835), Cosmetic compositions for hair treatment containing dendrimers or dendrimer conjugates.
US Patent (WO/2006/009451), Dendrimer-aminobutadiene-based UV-screens.
Vandamme TF, and Brobeck L. Effect of PAMAM dendrimers on ocular delivery of piliocarpine. J. Control. Release 102: 23-38 (2005).
Venuganti VV, and Perumal OP. Effect of poly (amidoamine) (PAMAM) dendrimer on skin permeation of 5-fluorouracil. Int. J. Pharm. 361: 230-38 (2008).
Wenjun Y, Yiyun C, Tongwen X, Xueyuan W, and Long-ping W. Targeting cancer cells with biotin-dendrimer conjugates. Eur. J. Med. Chem. (Press): 1-7 (2008)
Wiener EC. Delivery of diagnostic agents. Magn. Reson.Med. 31: 1–8 (1994).
Wooley KL, Hawker CJ, and Frechet JMJ. Hyperbranched macromolecule via a novel double stage convergent growth approach. J. Am. Chem. Soc. 113: 4583-85 (1991).
Wu H, Liu Z, Wang X, Zhao B, Zhang J, and Li C. Preparation of hollow capsule-stabilized gold nanoparticles through the encapsulation of the dendrimer. J. Colloid. Interface Sci. 302: 142–148 (2006).
Xu Y, and Zhao D. Removal of copper from contaminated soil by use of poly (amidoamine) dendrimers. Environ. Sci. Technol. 39: 2369–2375 (2005).
Zhuo RX, Du B, and Lu ZR. In vitro release of 5-fluorouracil with cyclic core dendritic polymer. J. Control. Release 57: 249-57 (1999).
