Understanding the Pharmaceutical Aspects of Dendrimers for the Delivery of Anticancer Drugs

Author(s): Sunil Kumar Dubey*, Shubham Salunkhe, Mukta Agrawal, Maithili Kali, Gautam Singhvi, Sanjay Tiwari, Swarnlata Saraf, Shailendra Saraf, Amit Alexander*

Journal Name: Current Drug Targets

Volume 21 , Issue 6 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Graphical Abstract:


Dendrimers are emerging class of nanoparticles used in targeted drug delivery systems. These are radially symmetric molecules with well-defined, homogeneous, and monodisperse structures. Due to the nano size, they can easily cross the biological membrane and increase bioavailability. The surface functionalization facilitates targeting of the particular site of action, assists the high drug loading and improves the therapeutic efficiency of the drug. These properties make dendrimers advantageous over conventional drug delivery systems. This article explains the features of dendrimers along with their method of synthesis, such as divergent growth method, convergent growth method, double exponential and mixed method, hyper-core and branched method. Dendrimers are effectively used in anticancer delivery and can be targeted at the site of tumor either by active or passive targeting. There are three mechanisms by which drugs interact with dendrimers, and they are physical encapsulation, electrostatic interaction, chemical conjugation of drug molecules. Drug releases from dendrimer either by in vivo cleavage of the covalent bond between drugdendrimer complexes or by physical changes or stimulus like pH, temperature, etc.

Keywords: Dendrimer, anti-cancer drug, tumor, nanoparticle, convergent growth method, divergent growth method.

Bredel, M.; Zentner, J. Brain-tumour drug resistance: the bare essentials. Lancet Oncol., 2002, 3(7), 397-406. [http://dx.doi.org/10.1016/S1470-2045(02)00786-6]. [PMID: 12142169].
Chittasupho, C.; Anuchapreeda, S.; Sarisuta, N. CXCR4 targeted dendrimer for anti-cancer drug delivery and breast cancer cell migration inhibition. European journal of pharmaceutics and biopharmaceutics. Eur. J. Pharm. Biopharm., 2017, 119, 310-321. [http://dx.doi.org/10.1016/j.ejpb.2017.07.003].
Pardridge, W.M. The blood-brain barrier: bottleneck in brain drug development. NeuroRx, 2005, 2(1), 3-14. [http://dx.doi.org/10.1602/neurorx.2.1.3].
Pardridge, W.M. Drug transport across the blood-brain barrier. J. Cereb. Blood Flow Metab., 2012, 32(11), 1959-1972. [http://dx.doi.org/10.1038/jcbfm.2012.126]. [PMID: 22929442].
Junyaprasert, V.B.; Morakul, B. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian Journal of Pharmaceutical Sciences, 2015, 10(1), 13-23. [http://dx.doi.org/10.1016/j.ajps.2014.08.005].
Tomalia, D.A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S. A new class of polymers: starburst-dendritic macromolecules. Polym. J., 1985, 17, 117. [http://dx.doi.org/10.1295/polymj.17.117].
Newkome, G.R.; Yao, Z.; Baker, G.R.; Gupta, V.K. Micelles. Part 1. Cascade molecules: a new approach to micelles. A [27]-arborol. J. Org. Chem., 1985, 50(11), 2003-2004. [http://dx.doi.org/10.1021/jo00211a052].
Pushkar, S.P.A.; Pathak, K.; Pathak, D. Dendrimers: Nanotechnology derived novel polymers in drug delivery. Indian Journal of Pharmaceutical Education and Research, 2006, 40(3), 153.
Patri, A.K.; Kukowska-Latallo, J.F.; Baker, J.R., Jr Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex. Adv. Drug Deliv. Rev., 2005, 57(15), 2203-2214. [http://dx.doi.org/10.1016/j.addr.2005.09.014]. [PMID: 16290254].
Yarema, SGSKJ Dendrimers in cancer treatment and diagnosis, 2007.
Kesavan, A.; Pakala, S.B.; Rayala, S.K.; Venkatraman, G. Effective strategies and applications of dendrimers in the treatment of ovarian cancer. Curr. Pharm. Des., 2017, 23(21), 3099-3104. [http://dx.doi.org/10.2174/1381612823666170223165541]. [PMID: 28240171].
Gillies, E.R.; Fréchet, J.M. Dendrimers and dendritic polymers in drug delivery. Drug Discov. Today, 2005, 10(1), 35-43. [http://dx.doi.org/10.1016/S1359-6446(04)03276-3]. [PMID: 15676297].
Agarwal, A.; Asthana, A.; Gupta, U.; Jain, N.K. Tumour and dendrimers: a review on drug delivery aspects. J. Pharm. Pharmacol., 2008, 60(6), 671-688. [http://dx.doi.org/10.1211/jpp.60.6.0001]. [PMID: 18498702].
Ardestani, M.S.; Fordoei, A.S.; Abdoli, A. Nanosilver based anionic linear globular dendrimer with a special significant antiretroviral activity. J. Mater. Sci. Mater. Med., 2015, 26(5), 179. [http://dx.doi.org/10.1007/s10856-015-5510-7]. [PMID: 25893388].
Dwivedi, N.; Shah, J.; Mishra, V. Dendrimer-mediated approaches for the treatment of brain tumor. J. Biomater. Sci. Polym. Ed., 2016, 27(7), 557-580. [http://dx.doi.org/10.1080/09205063.2015.1133155]. [PMID: 26928261].
Mishra, V.; Kesharwani, P. Dendrimer technologies for brain tumor. Drug Discov. Today, 2016, 21(5), 766-778. [http://dx.doi.org/10.1016/j.drudis.2016.02.006]. [PMID: 26891979].
Jain, A.; Jain, K.; Kesharwani, P.; Jain, N.K. Low density lipoproteins mediated nanoplatforms for cancer targeting. J. Nanopart. Res., 2013, 15(9), 1888. [http://dx.doi.org/10.1007/s11051-013-1888-7].
Jain, A.; Jain, K.; Mehra, N.K.; Jain, N.K. Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells. J. Nanopart. Res., 2013, 15(10), 2003. [http://dx.doi.org/10.1007/s11051-013-2003-9].
Mignani, S.; Rodrigues, J.; Tomas, H. Dendrimers in combination with natural products and analogues as anti-cancer agents. Chem. Soc. Rev., 2018, 47(2), 514-532. [http://dx.doi.org/10.1039/C7CS00550D]. [PMID: 29154385].
Gupta, U.; Dwivedi, S.K.; Bid, H.K.; Konwar, R.; Jain, N.K. Ligand anchored dendrimers based nanoconstructs for effective targeting to cancer cells. Int. J. Pharm., 2010, 393(1-2), 185-196. [http://dx.doi.org/10.1016/j.ijpharm.2010.04.002]. [PMID: 20382210].
Singh, J.; Jain, K.; Mehra, N.K.; Jain, N.K. Dendrimers in anticancer drug delivery: mechanism of interaction of drug and dendrimers. Artif. Cells Nanomed. Biotechnol., 2016, 44(7), 1626-1634. [http://dx.doi.org/10.3109/21691401.2015.1129625]. [PMID: 26747336].
Tomalia, D.A.; Fréchet, J.M.J. Discovery of dendrimers and dendritic polymers: A brief historical perspective. J. Polym. Sci. A Polym. Chem., 2002, 40(16), 2719-2728. [http://dx.doi.org/10.1002/pola.10301].
Gajbhiye, V.; Palanirajan, V.K.; Tekade, R.K.; Jain, N.K. Dendrimers as therapeutic agents: a systematic review. J. Pharm. Pharmacol., 2009, 61(8), 989-1003. [http://dx.doi.org/10.1211/jpp.61.08.0002]. [PMID: 19703342].
Atav, R. 8 - Dendritic molecules and their use in water repellency treatments of textile materials; Waterproof and Water Repellent Textiles and Clothing, 2018, pp. 191-214. [http://dx.doi.org/10.1016/B978-0-08-101212-3.00007-1]
Fischer, M.; Vögtle, F. Dendrimers: from design to application-a progress report. Angew. Chem. Int. Ed. Engl., 1999, 38(7), 884-905. [http://dx.doi.org/10.1002/(SICI)1521-3773(19990401)38:7<884: AID-ANIE884>3.0.CO;2-K]. [PMID: 29711851].
Cadena, L-E.S.; Gauthier, M. Phase-segregated dendrigraft copolymer architectures. Polymers (Basel), 2010, 2(4), 596. [http://dx.doi.org/10.3390/polym2040596].
Bolu, B.S.; Sanyal, R.; Sanyal, A. Drug delivery systems from self-assembly of dendron-polymer conjugates. Molecules, 2018, 23(7)E1570 [http://dx.doi.org/10.3390/molecules23071570]. [PMID: 29958437].
Chaumette, J-L.; Laufersweiler, M.J.; Parquette, J.R. Synthesis and chiroptical properties of dendrimers elaborated from a chiral, nonracemic central core. J. Org. Chem., 1998, 63(25), 9399-9405. [http://dx.doi.org/10.1021/jo981508b].
Jain, K.; Verma, A.K.; Mishra, P.R.; Jain, N.K. Characterization and evaluation of amphotericin B loaded MDP conjugated poly(propylene imine) dendrimers. Nanomedicine (Lond.), 2015, 11(3), 705-713. [http://dx.doi.org/10.1016/j.nano.2014.11.008]. [PMID: 25596078].
Meier, W. Polymer nanocapsules. Chem. Soc. Rev., 2000, 29(5), 295-303. [http://dx.doi.org/10.1039/a809106d].
Jain, K.; Gupta, U.; Jain, N.K. Dendronized nanoconjugates of lysine and folate for treatment of cancer. Eur. J. Pharm. Biopharm., 2014, 87(3), 500-509. [http://dx.doi.org/10.1016/j.ejpb.2014.03.015].
He, X.; Alves, C.S.; Oliveira, N. RGD peptide-modified multifunctional dendrimer platform for drug encapsulation and targeted inhibition of cancer cells. Colloids Surf. B Biointerfaces, 2015, 125, 82-89. [http://dx.doi.org/10.1016/j.colsurfb.2014.11.004]. [PMID: 25437067].
Palmerston Mendes, L.; Pan, J.; Torchilin, V.P. Dendrimers as nanocarriers for nucleic acid and drug delivery in cancer therapy. Molecules, 2017, 22(9)E1401 [http://dx.doi.org/10.3390/molecules22091401]. [PMID: 28832535].
Liu, Y.; Pang, Y.; Toh, M.R.; Chiu, G.N.C. Dual-functionalized poly(amidoamine) dendrimers with poly(ethylene glycol) conjugation and thiolation improved blood compatibility. J. Pharm. Pharmacol., 2015, 67(11), 1492-1502. [http://dx.doi.org/10.1111/jphp.12457]. [PMID: 26303576].
She, W.; Pan, D.; Luo, K. PEGylated dendrimer-doxorubicin cojugates as ph-sensitive drug delivery systems: synthesis and in vitro characterization. J. Biomed. Nanotechnol., 2015, 11(6), 964-978. [http://dx.doi.org/10.1166/jbn.2015.1865]. [PMID: 26353586].
Esfand, R.; Tomalia, D.A. Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. Drug Discov. Today, 2001, 6(8), 427-436. [http://dx.doi.org/10.1016/S1359-6446(01)01757-3]. [PMID: 11301287].
Lalwani, S.; Chouai, A.; Perez, L.M.; Santiago, V.; Shaunak, S.; Simanek, E.E. Mimicking PAMAM Dendrimers with Ampholytic, Hybrid Triazine Dendrimers: A Comparison of Dispersity and Stability. Macromolecules, 2009, 42(17), 6723-3732. [http://dx.doi.org/10.1021/ma9011818]. [PMID: 20711424].
Xu, L.; Yeudall, W.A.; Yang, H. Folic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and sustained highly localized retention in solid tumors: Its utility for local siRNA delivery. Acta Biomater., 2017, 57, 251-261. [http://dx.doi.org/10.1016/j.actbio.2017.04.023]. [PMID: 28438704].
Shukla, S.K.; Govender, P.P.; Tiwari, A. Chapter six - polymeric micellar structures for biosensor technology. Advances in Biomembranes and Lipid Self-Assembly, 2016, 24, 143-161.
Wu, J.; Huang, W.; He, Z. Dendrimers as carriers for siRNA delivery and gene silencing: a review. ScientificWorldJournal, 2013, •••2013630654 [http://dx.doi.org/10.1155/2013/630654]. [PMID: 24288498].
Ohsaki, M.; Okuda, T.; Wada, A.; Hirayama, T.; Niidome, T.; Aoyagi, H. In vitro gene transfection using dendritic poly(L-lysine). Bioconjug. Chem., 2002, 13(3), 510-517. [http://dx.doi.org/10.1021/bc015525a]. [PMID: 12009940].
Kaminskas, LM; Kelly, BD; McLeod, VM; Sberna, G; Owen, DJ; Boyd, BJ et al. Characterisation and tumour targeting of PEGylated polylysine dendrimers bearing doxorubicin via a pH labile linker. Journal of controlled release: official journal of the Controlled Release Society 2011; 152(2): 241-8.
Deschenaux, R.; Donnio, B.; Guillon, D. Liquid-crystalline fullerodendrimers. New J. Chem., 2007, 31(7), 1064-1073. [http://dx.doi.org/10.1039/b617671m].
Meier, H.; Lehmann, M.; Kolb, U. Stilbenoid dendrimers. Chemistry, 2000, 6(13), 2462-2469. [http://dx.doi.org/10.1002/1521-3765(20000703)6:13<2462:AID-CHEM2462>3.0.CO;2-A]. [PMID: 10939748].
Zhu, J.; Faria, J.L.; Figueiredo, J.L.; Thomas, A. Reaction mechanism of aerobic oxidation of alcohols conducted on activated-carbon-supported cobalt oxide catalysts. Chemistry, 2011, 17(25), 7112-7117. [http://dx.doi.org/10.1002/chem.201003025]. [PMID: 21557343].
Lim, J.; Simanek, E.E. Synthesis of water-soluble dendrimers based on melamine bearing 16 paclitaxel groups. Org. Lett., 2008, 10(2), 201-204. [http://dx.doi.org/10.1021/ol7024907]. [PMID: 18088131].
Rasines, B; Hernandez-Ros, JM; de las Cuevas, N; Copa-Patino, JL; Soliveri, J; Munoz-Fernandez, MA Water-stable ammonium-terminated carbosilane dendrimers as efficient antibacterial agents. Dalton transactions (Cambridge, England 2003) 2009; 2009(40): 8704-13.,
Yamada, A.; Hatano, K.; Matsuoka, K.; Koyama, T.; Esumi, Y.; Koshino, H. Syntheses and Vero toxin-binding activities of carbosilane dendrimers periphery-functionalized with galabiose. Tetrahedron, 2006, 62(21), 5074-5083. [http://dx.doi.org/10.1016/j.tet.2006.03.042].
Ferenc, M.; Pedziwiatr-Werbicka, E.; Nowak, K.E.; Klajnert, B.; Majoral, J.P.; Bryszewska, M. Phosphorus dendrimers as carriers of siRNA--characterisation of dendriplexes. Molecules, 2013, 18(4), 4451-4466. [http://dx.doi.org/10.3390/molecules18044451]. [PMID: 23591925].
Solassol, J.; Crozet, C.; Perrier, V. Cationic phosphorus-containing dendrimers reduce prion replication both in cell culture and in mice infected with scrapie. J. Gen. Virol., 2004, 85(Pt 6), 1791-1799. [http://dx.doi.org/10.1099/vir.0.19726-0]. [PMID: 15166465].
Dvornic, P.R. PAMAMOS: The first commercial silicon-containing dendrimers and their applications. J. Polym. Sci. A Polym. Chem., 2006, 44(9), 2755-2773. [http://dx.doi.org/10.1002/pola.21368].
Tomalia, D.A. Birth of a new macromolecular architecture: dendrimers as quantized building blocks for nanoscale synthetic polymer chemistry. Prog. Polym. Sci., 2005, 30(3), 294-324. [http://dx.doi.org/10.1016/j.progpolymsci.2005.01.007].
Jackson, C.L.; Chanzy, H.D.; Booy, F.P.; Drake, B.J.; Tomalia, D.A.; Bauer, B.J. Visualization of dendrimer molecules by transmission electron microscopy (tem): staining methods and cryo-tem of vitrified solutions. Macromolecules, 1998, 31(18), 6259-6265. [http://dx.doi.org/10.1021/ma9806155].
Maciejewski, M. Concepts of trapping topologically by shell molecules. J Macromolecular Science: Part A - Chemistry, 1982, 17(4), 689-703. [http://dx.doi.org/10.1080/00222338208062416].
Chaplot, S.P.; Rupenthal, I.D. Dendrimers for gene delivery--a potential approach for ocular therapy? J. Pharm. Pharmacol., 2014, 66(4), 542-556. [http://dx.doi.org/10.1111/jphp.12104]. [PMID: 24635556].
Cheng, Y.; Xu, Z.; Ma, M.; Xu, T. Dendrimers as drug carriers: applications in different routes of drug administration. J. Pharm. Sci., 2008, 97(1), 123-143. [http://dx.doi.org/10.1002/jps.21079]. [PMID: 17721949].
Silva, A.C.; Lopes, C.M.; Lobo, J.M.; Amaral, M.H. Delivery systems for biopharmaceuticals. Part II: Liposomes, Micelles, Microemulsions and Dendrimers. Curr. Pharm. Biotechnol., 2015, 16(11), 955-965. [http://dx.doi.org/10.2174/1389201016666150817094637]. [PMID: 26278524].
Mourey, T.H.; Turner, S.R.; Rubinstein, M.; Frechet, J.M.J.; Hawker, C.J.; Wooley, K.L. Unique behavior of dendritic macromolecules: intrinsic viscosity of polyether dendrimers. Macromolecules, 1992, 25(9), 2401-2406. [http://dx.doi.org/10.1021/ma00035a017].
Fréchet, J.M. Functional polymers and dendrimers: reactivity, molecular architecture, and interfacial energy. Science, 1994, 263(5154), 1710-1715. [http://dx.doi.org/10.1126/science.8134834]. [PMID: 8134834].
Jansen, J.F.; de Brabander-van den Berg, E.M.; Meijer, E.W. Encapsulation of guest molecules into a dendritic box. Science, 1994, 266(5188), 1226-1229. [http://dx.doi.org/10.1126/science.266.5188.1226]. [PMID: 17810265].
Ekkelenkamp, A.E.; Elzes, M.R.; Engbersen, J.F.J.; Paulusse, J.M.J. Responsive crosslinked polymer nanogels for imaging and therapeutics delivery. J. Mater. Chem. B Mater. Biol. Med., 2018, 6(2), 210-235. [http://dx.doi.org/10.1039/C7TB02239E].
Duncan, R.; Izzo, L. Dendrimer biocompatibility and toxicity. Adv. Drug Deliv. Rev., 2005, 57(15), 2215-2237. [http://dx.doi.org/10.1016/j.addr.2005.09.019]. [PMID: 16297497].
Ríhová, B.; Ulbrich, K.; Kopecek, J.; Mancal, P. Immunogenicity of N-(2-hydroxypropyl)-methacrylamide copolymers--potential hapten or drug carriers. Folia Microbiol. (Praha), 1983, 28(3), 217-227. [http://dx.doi.org/10.1007/BF02884085]. [PMID: 6873772].
Seymour, L.W.; Duncan, R.; Strohalm, J.; Kopecek, J. Effect of molecular weight (Mw) of N-(2-hydroxypropyl)methacrylamide copolymers on body distribution and rate of excretion after subcutaneous, intraperitoneal, and intravenous administration to rats. J. Biomed. Mater. Res., 1987, 21(11), 1341-1358. [http://dx.doi.org/10.1002/jbm.820211106]. [PMID: 3680316].
Svenson, S.; Tomalia, D.A. Dendrimers in biomedical applications--reflections on the field. Adv. Drug Deliv. Rev., 2005, 57(15), 2106-2129. [http://dx.doi.org/10.1016/j.addr.2005.09.018]. [PMID: 16305813].
Yu, G.S.; Bae, Y.M.; Choi, H.; Kong, B.; Choi, I.S.; Choi, J.S. Synthesis of PAMAM dendrimer derivatives with enhanced buffering capacity and remarkable gene transfection efficiency. Bioconjug. Chem., 2011, 22(6), 1046-1055. [http://dx.doi.org/10.1021/bc100479t]. [PMID: 21528924].
Majoros, I.J.; Williams, C.R.; Tomalia, D.A.; Baker, J.R., Jr New Dendrimers: Synthesis and Characterization of Popam - Pamam Hybrid Dendrimers. Macromolecules, 2008, 41(22), 8372-8379. [http://dx.doi.org/10.1021/ma801843a]. [PMID: 21258604].
Hawker, C.J.; Frechet, J.M.J. Preparation of polymers with controlled molecular architecture. A new convergent approach to dendritic macromolecules. J. Am. Chem. Soc., 1990, 112(21), 7638-7647. [http://dx.doi.org/10.1021/ja00177a027].
Liu, M.; Fréchet, J.M. Designing dendrimers for drug delivery. Pharm. Sci. Technol. Today, 1999, 2(10), 393-401. [http://dx.doi.org/10.1016/S1461-5347(99)00203-5]. [PMID: 10498919].
Kawaguchi, T.; Walker, K.L.; Wilkins, C.L.; Moore, J.S. Double Exponential Dendrimer Growth. J. Am. Chem. Soc., 1995, 117(8), 2159-2165. [http://dx.doi.org/10.1021/ja00113a005].
Sowinska, M.; Urbanczyk-Lipkowska, Z. Advances in the chemistry of dendrimers. New J. Chem., 2014, 38(6), 2168-2203. [http://dx.doi.org/10.1039/c3nj01239e].
Pasut, G.; Veronese, F.M. Polymer–drug conjugation, recent achievements and general strategies. Prog. Polym. Sci., 2007, 32(8), 933-961. [http://dx.doi.org/10.1016/j.progpolymsci.2007.05.008].
Abbasi, E.; Aval, S.F.; Akbarzadeh, A. Dendrimers: synthesis, applications, and properties. Nanoscale Res. Lett., 2014, 9(1), 247. [http://dx.doi.org/10.1186/1556-276X-9-247]. [PMID: 24994950].
Lammers, T; Kiessling, F; Hennink, WE; Storm, G Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. Journal of controlled release: official journal of the Controlled Release Society 2012; 161(2): 175-87.
Holback, H.; Yeo, Y. Intratumoral drug delivery with nanoparticulate carriers. Pharm. Res., 2011, 28(8), 1819-1830. [http://dx.doi.org/10.1007/s11095-010-0360-y]. [PMID: 21213021].
Markovsky, E.; Baabur-Cohen, H.; Eldar-Boock, A.; Omer, L.; Tiram, G.; Ferber, S. Administration, distribution, metabolism and elimination of polymer therapeutics. J. Control. Release, 2012, 161(2), 446-460. [http://dx.doi.org/10.1016/j.jconrel.2011.12.021].
Bertrand, N.; Leroux, J.C. The journey of a drug-carrier in the body: an anatomo-physiological perspective. J. Control. Release, 2012, 161(2), 152-163. [http://dx.doi.org/10.1016/j.jconrel.2011.09.098].
Medina, S.H.; El-Sayed, M.E.H. Dendrimers as carriers for delivery of chemotherapeutic agents. Chem. Rev., 2009, 109(7), 3141-3157. [http://dx.doi.org/10.1021/cr900174j]. [PMID: 19534493].
Maeda, H; Wu, J; Sawa, T; Matsumura, Y; Hori, K Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. Journal of controlled release: official journal of the Controlled Release Society 2000; 65(1-2): 271-84.,
Matsumura, Y.; Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res., 1986, 46(12 Pt 1), 6387-6392. [PMID: 2946403].
El-Sayed, M.; Kiani, M.F.; Naimark, M.D.; Hikal, A.H.; Ghandehari, H. Extravasation of poly(amidoamine) (PAMAM) dendrimers across microvascular network endothelium. Pharm. Res., 2001, 18(1), 23-28. [http://dx.doi.org/10.1023/A:1011066408283]. [PMID: 11336349].
Battah, S.; Balaratnam, S.; Casas, A. Macromolecular delivery of 5-aminolaevulinic acid for photodynamic therapy using dendrimer conjugates. Mol. Cancer Ther., 2007, 6(3), 876-885. [http://dx.doi.org/10.1158/1535-7163.MCT-06-0359]. [PMID: 17363482].
Nigavekar, S.S.; Sung, L.Y.; Llanes, M. 3H dendrimer nanoparticle organ/tumor distribution. Pharm. Res., 2004, 21(3), 476-483. [http://dx.doi.org/10.1023/B:PHAM.0000019302.26097.cc]. [PMID: 15070099].
Howell, B.A.; Fan, D. Poly(amidoamine) dendrimer-supported organoplatinum antitumour agents. Proc.- Royal Soc., Math. Phys. Eng. Sci., 2010, 466(2117), 1515-1526. [http://dx.doi.org/10.1098/rspa.2009.0359].
Shi, C.; He, Y.; Feng, X.; Fu, D. ε-Polylysine and next-generation dendrigraft poly-L-lysine: chemistry, activity, and applications in biopharmaceuticals. J. Biomater. Sci. Polym. Ed., 2015, 26(18), 1343-1356. [http://dx.doi.org/10.1080/09205063.2015.1095023]. [PMID: 26381379].
Wijagkanalan, W.; Kawakami, S.; Hashida, M. Designing dendrimers for drug delivery and imaging: pharmacokinetic considerations. Pharm. Res., 2011, 28(7), 1500-1519. [http://dx.doi.org/10.1007/s11095-010-0339-8]. [PMID: 21181549].
Kesharwani, P.; Tekade, R.K.; Gajbhiye, V.; Jain, K.; Jain, N.K. Cancer targeting potential of some ligand-anchored poly(propylene imine) dendrimers: a comparison. Nanomedicine (Lond.), 2011, 7(3), 295-304. [http://dx.doi.org/10.1016/j.nano.2010.10.010]. [PMID: 21070888].
Avti, P.K.; Kakkar, A. Dendrimers as anti-inflammatory agents. Braz. J. Pharm. Sci., 2013, 49, 57-65. [http://dx.doi.org/10.1590/S1984-82502013000700006].
Taratula, O.; Schumann, C.; Naleway, M.A.; Pang, A.J.; Chon, K.J.; Taratula, O. A multifunctional theranostic platform based on phthalocyanine-loaded dendrimer for image-guided drug delivery and photodynamic therapy. Mol. Pharm., 2013, 10(10), 3946-3958. [http://dx.doi.org/10.1021/mp400397t]. [PMID: 24020847].
Tomalia, D.A.; Naylor, A.M.; Goddard, W.A., III Starburst dendrimers: molecular-level control of size, shape, surface chemistry, topology, and flexibility from atoms to macroscopic matter. Angew. Chem. Int. Ed. Engl., 1990, 29(2), 138-175. [http://dx.doi.org/10.1002/anie.199001381].
Milhem, O.M.; Myles, C.; McKeown, N.B.; Attwood, D.; D’Emanuele, A. Polyamidoamine Starburst dendrimers as solubility enhancers. Int. J. Pharm., 2000, 197(1-2), 239-241. [http://dx.doi.org/10.1016/S0378-5173(99)00463-9]. [PMID: 10704811].
Madaan, K.; Kumar, S.; Poonia, N.; Lather, V.; Pandita, D. Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues. J. Pharm. Bioallied Sci., 2014, 6(3), 139-150. [http://dx.doi.org/10.4103/0975-7406.130965]. [PMID: 25035633].
Luo, T.; Loira-Pastoriza, C.; Patil, H.P.; Ucakar, B.; Muccioli, G.G.; Bosquillon, C. PEGylation of paclitaxel largely improves its safety and anti-tumor efficacy following pulmonary delivery in a mouse model of lung carcinoma. J. Control. Release, 2016, 239, 62-71. [http://dx.doi.org/10.1016/j.jconrel.2016.08.008].
Choudhary, S.; Gupta, L.; Rani, S.; Dave, K.; Gupta, U. Impact of dendrimers on solubility of hydrophobic drug molecules. Front. Pharmacol., 2017, 8, 261. [http://dx.doi.org/10.3389/fphar.2017.00261]. [PMID: 28559844].
Zhong, Q.; Bielski, E.R.; Rodrigues, L.S.; Brown, M.R.; Reineke, J.J.; da Rocha, S.R. Conjugation to poly(amidoamine) dendrimers and pulmonary delivery reduce cardiac accumulation and enhance antitumor activity of doxorubicin in lung metastasis. Mol. Pharm., 2016, 13(7), 2363-2375. [http://dx.doi.org/10.1021/acs.molpharmaceut.6b00126]. [PMID: 27253493].
Kulhari, H.; Pooja, D.; Shrivastava, S. Trastuzumab-grafted PAMAM dendrimers for the selective delivery of anticancer drugs to HER2-positive breast cancer. Sci. Rep., 2016, 6, 23179. [http://dx.doi.org/10.1038/srep23179]. [PMID: 27052896].
Sanyakamdhorn, S.; Bekale, L.; Agudelo, D.; Tajmir-Riahi, H.A. Structural analysis of doxorubicin-polymer conjugates. Colloids Surf. B Biointerfaces, 2015, 135, 175-182. [http://dx.doi.org/10.1016/j.colsurfb.2015.07.070]. [PMID: 26255162].
Sanyakamdhorn, S.; Agudelo, D.; Bekale, L.; Tajmir-Riahi, H.A. Targeted conjugation of breast anticancer drug tamoxifen and its metabolites with synthetic polymers. Colloids Surf. B Biointerfaces, 2016, 145, 55-63. [http://dx.doi.org/10.1016/j.colsurfb.2016.04.035]. [PMID: 27137803].
Wolinsky, J.B.; Grinstaff, M.W. Therapeutic and diagnostic applications of dendrimers for cancer treatment. Adv. Drug Deliv. Rev., 2008, 60(9), 1037-1055. [http://dx.doi.org/10.1016/j.addr.2008.02.012]. [PMID: 18448187].
Kesharwani, P.; Tekade, R.K.; Jain, N.K. Generation dependent safety and efficacy of folic acid conjugated dendrimer based anticancer drug formulations. Pharm. Res., 2015, 32(4), 1438-1450. [http://dx.doi.org/10.1007/s11095-014-1549-2]. [PMID: 25330744].
Jain, N.K.; Tare, M.S.; Mishra, V.; Tripathi, P.K. The development, characterization and in vivo anti-ovarian cancer activity of poly(propylene imine) (PPI)-antibody conjugates containing encapsulated paclitaxel. Nanomedicine (Lond.), 2015, 11(1), 207-218. [http://dx.doi.org/10.1016/j.nano.2014.09.006]. [PMID: 25262579].
Al-Jamal, K.T.; Al-Jamal, W.T.; Wang, J.T. Cationic poly-L-lysine dendrimer complexes doxorubicin and delays tumor growth in vitro and in vivo. ACS Nano, 2013, 7(3), 1905-1917. [http://dx.doi.org/10.1021/nn305860k]. [PMID: 23527750].
Niidome, T.; Yamauchi, H.; Takahashi, K. Hydrophobic cavity formed by oligopeptide for doxorubicin delivery based on dendritic poly(L-lysine). J. Biomater. Sci. Polym. Ed., 2014, 25(13), 1362-1373. [http://dx.doi.org/10.1080/09205063.2014.938979]. [PMID: 25040893].
Malik, N.; Wiwattanapatapee, R.; Klopsch, R.; Lorenz, K.; Frey, H.; Weener, J.W. Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. J. Control. Release, 2000, 65(1-2), 133-148.
Padilla De Jesús, O.L.; Ihre, H.R.; Gagne, L.; Fréchet, J.M.; Szoka, F.C., Jr Polyester dendritic systems for drug delivery applications: in vitro and in vivo evaluation. Bioconjug. Chem., 2002, 13(3), 453-461. [http://dx.doi.org/10.1021/bc010103m]. [PMID: 12009933].
Ihre, H.R.; Padilla De Jesús, O.L.; Szoka, F.C., Jr; Fréchet, J.M. Polyester dendritic systems for drug delivery applications: design, synthesis, and characterization. Bioconjug. Chem., 2002, 13(3), 443-452. [http://dx.doi.org/10.1021/bc010102u]. [PMID: 12009932].
Sadekar, S.; Ghandehari, H. Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery. Adv. Drug Deliv. Rev., 2012, 64(6), 571-588. [http://dx.doi.org/10.1016/j.addr.2011.09.010]. [PMID: 21983078].
Chen, H.T.; Neerman, M.F.; Parrish, A.R.; Simanek, E.E. Cytotoxicity, hemolysis, and acute in vivo toxicity of dendrimers based on melamine, candidate vehicles for drug delivery. J. Am. Chem. Soc., 2004, 126(32), 10044-10048. [http://dx.doi.org/10.1021/ja048548j]. [PMID: 15303879].
Roberts, J.C.; Bhalgat, M.K.; Zera, R.T. Preliminary biological evaluation of polyamidoamine (PAMAM) Starburst dendrimers. J. Biomed. Mater. Res., 1996, 30(1), 53-65. [http://dx.doi.org/10.1002/(SICI)1097-4636(199601)30:1<53:AID-JBM8>3.0.CO;2-Q]. [PMID: 8788106].

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [528 - 540]
Pages: 13
DOI: 10.2174/1389450120666191031092259
Price: $65

Article Metrics

PDF: 29
PRC: 1