Pharmaceutical Applications and Safety Review of Dendrimers
DOI:
https://doi.org/10.37285/ijpsn.2019.12.4.1Abstract
This article describes the innovative approaches to overcome the cationic toxicity inherently associated with the dendrimers. A dendrimer is a macromolecule characterized by its highly branched 3D structure that provides a high degree of surface functionality and versatility. The toxicity is attributed to the interaction of surface cationic charge of dendrimers with negatively charged biological membranes in vivo. Dendrimer toxicity in biological system is generally characterized by hemolytic toxicity, cytotoxicity and hematological toxicity. To minimize this toxicity, two strategies have been utilized; first, designing and synthesis of biocompatible dendrimers; and second, masking of peripheral charge of dendrimers by surface engineering. Biocompatible dendrimers can be synthesized by employing biodegradable core and branching units or utilizing intermediates of various metabolic pathways. Dendrimer biocompatibility has been evaluated in vitro and in vivo for efficient presentation of biological performance. Neutral and negatively charged dendrimers do not interact with biological environment and hence are compatible for clinical applications as elucidated by various studies examined in this review. Chemical modification of the surface is an important strategy to overcome the toxicity problems associated with the dendrimers.
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Keywords:
Dendrimers, Hemolytic toxicity, Cytotoxicity, Dendrimer safety
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Published
2019-07-31
How to Cite
1.
Nayak J, Tripathi PK, Verma NK, Mishra JN. Pharmaceutical Applications and Safety Review of Dendrimers. Scopus Indexed [Internet]. 2019 Jul. 31 [cited 2024 Nov. 19];12(4):4565-72. Available from: https://ijpsnonline.com/index.php/ijpsn/article/view/304
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Section
Review Articles
References
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Anne-Noëlle Petit, Philippe Eullaffroy, Timothée Debenest, Francois Gagnéa (2010). Toxicity of PAMAM dendrimers to Chlamydomonas reinhardtii, Aquatic Toxicology 100: 187-193.
Antonio Quintana, Ewa Raczka,et.al. (2002). Design and Function of a Dendrimer-Based Therapeutic Nanodevice Targeted to Tumor Cells Through the Folate Receptor, Pharmaceutical Research, Vol. 19, 21-23.
Barabara K. and B. Maria (2001). Review Dendrimers: properties and applications. Acta Biochimi Polonica, 48: 199-208.
Chauhan, A.S., Jain, N.K. and Diwan, P. (2009). PAMAM Dendrimers in mice Pre-clinical and behavioural toxicity profile of, proceeding the royal of society. Proc. R. Soc, pp. 466.
Cheng Y, Man N, Xu T, Fu R, Wang X, Wang X and Wen L, (2007). Transdermal delivery of nonsteroidal anti-inflammatory drugs mediated by polyamidoamine [PAMAM] dendrimers, J. Pharm. Sci., 96: 595-602.
Csaba N, Garcia-Fuentes M and Alonso M.J, (2006). The performance of nanocarriers for transmucosal drug delivery, Expert. Opin. Drug Deliv, 3: 463-478.
Daniel Q. McNerny, Pascale R. Leroueil and James R. Baker (2010). Understanding specific and nonspecific toxicities: a requirement for the development of dendrimer-based pharmaceuticals, Advance review, John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol, 2: 249-259
Frechet J.M.J. and D.A. Tomalia, (2001). Introduction to the Dendritic state: Dendrimers and other Dendritic Polymers. John Wiley and Sons Ltd.
Giridhar Thiagarajan, Khaled Greish and Hamidreza Ghandehari (2013). Charge affects the oral toxicity of poly[amidoamine] dendrimers, European Journal of Pharmaceutics and Biopharmaceutics. 84(2): 330-4.
H.N.Patel and Dr. P.M.Patel, (2013). Dendrimer Applications – A Review, Int J Pharm Bio Sci 4: 454-463.
Hawaker, C., K.L. Wooley and J.M.J. Frechet, (1993). Journal of Chemical Society. Perkin Transactions, 1: 1287-1289.
I.B. Erick (2006). Engeineering Dendrimer for Biological Application, Frontiers in chemistry.
Jaeschke, H. Gores, G.J. Cederbaum, A.I, Hinson, J.A. Pessayre, D. and Lemasters J.J., (2002). Mechanisms of hepatotoxicity. Toxicol. Sci. 65: 166-76.
Jevprasesphant R. Penny J. Jalal R. Attwood, D., McKeown, N.B., and A.D Emanuele (2003). The influence of surface modification on the cytotoxicity of PAMAM Dendrimers. Int J Pharm, 252: 263-266.
K. Inoue, (2000) Functional dendrimers, hyperbranched and star polymers, Prog. Polym. Sci. 25: 453-571.
Keerti Jain, Prashant Kesharwani, Umesh Gupta, and N. K. Jain, (2010). Dendrimer toxicity: Let’s meet the challenge, International Journal of Pharmaceutics 394: 122-142.
Kukowska-Latallo JF, Bielinska AU, Johnson J, Spindler R, Tomalia DA, et al. (1996). Efficient transfer of genetic material into mammalian cells using starburst polyamidoamine dendrimers. Proc Natl Acad Sci USA 93: 4897-4902.
Malik N, Wiwattanapatapee R, Klopsch R, Lorenz K, Frey H, et al (2000). Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. J Control Release, 65: 133-148.
Mohammad, N. and D. Antony, (2006). Crossing cellular barriers using dendrimers nanotechnologies. Current Opinion in Pharmacology 6: 522-527.
Nanjwade B.K., Kishore V.S. and Thakare S. A., (2011). Novel Drug Delivery Systems and Regulatory Affairs. IKON BOOKS, Publishers and Distributors, New Delhi, 1-4: 29-33.
P. Sedl´akov´a, J. Svobodov´a, I. Mikˇs´ık a and H. Tom (2006). as Separation of poly[amidoamine] [PAMAM] dendrimer generations by dynamic coating capillary electrophoresis, , Journal of Chromatography B, 841 135–139.
Patel RP et al. (2007). Dendrimers: A new innovation in drug delivery”, Pharma Bio World, 42-52.
Pushkar, S., A. Philip, K. Pathak and D. Pathak (2006). Dendrimers: Nanotechnology Derived Novel Polymers in Drug Delivery. Indian Journal of Pharmaceutical Education and Research, 40: 153-158.
S. Sadekar A.C. and H. Ghandehari, (2012). Transepithelial transport and toxicity of PAMAM dendrimers: Implications for oral drug delivery, Advaned Drug Delivery Reviews 64: 571-588.
Sadekar, S. and Ghandehar,i H., (2012). Transepithelial transport and toxicity of PAMAM Dendrimers Implications for oral drug delivery. Advanced Drug Delivery Reviews, 64: 571–588
Scott H. Medina and Mohamed E. H. El-Sayed*(2009). Dendrimers as Carriers for Delivery of Chemotherapeutic Agents, Chem. Rev. 109: 3141-3157.
Sivabalan, M. and Jeyapragash, R. (2013). Dendrimer: A Novel Polymer. IJRPC, Vol. 3, Issue 2 .
Sonke, S. and Tomalia D.A. (2005). Dendrimers in biomedical application reflection on the field. Advanced Drug Delivery Reviews, 57: 2106-2129.
Srinivasa-Gopalan Sampathkumar, and Kevin J. Yarema, Dendrimers in Cancer Treatment and Diagnosis. Nanotechnologies for the Life Sciences 7: 31387-97.
Tatiana Tocchini Felippotti, ScDa, et.al. (2011). Effect of a nanostructured dendrimer-naloxonazine complex on endogenous opioid peptides μ1 receptor-mediated post-ictal antinociception, Nanomedicine: Nanotechnology, Biology, and Medicine 7(6): 871-880.
Tolia G.T, Choi H.H and Ahsan F (2008). The role of dendrimers in drug delivery, Pharmaceut. Tech 32: 88-98.
Tomalia D. A., Naylor A. M., and. Goddard W. A. (1990). Starburst dendrimers: molecular-level control of size, shape, surface chemistry,topology, and flexibility from atoms to macroscopic 8matter. Angew. Chem. Int. Ed. 29: 138-175.
Tomalia, D.A., (2005). Birth of a new macromolecular architecture Dendrimers as quantized building blocks for nanoscale synthetic polymer chemistr. Prog. Polym. Sci 30: 294-324.
Trivedi, V. Patel, U. Daslaniya, Patel G, Bhiman,i B. Dhiren and Vyas B (2012). Dendrimer Polymer of 21 St Century, Vol. 1, Issue 2.
Anne-Noëlle Petit, Philippe Eullaffroy, Timothée Debenest, Francois Gagnéa (2010). Toxicity of PAMAM dendrimers to Chlamydomonas reinhardtii, Aquatic Toxicology 100: 187-193.
Antonio Quintana, Ewa Raczka,et.al. (2002). Design and Function of a Dendrimer-Based Therapeutic Nanodevice Targeted to Tumor Cells Through the Folate Receptor, Pharmaceutical Research, Vol. 19, 21-23.
Barabara K. and B. Maria (2001). Review Dendrimers: properties and applications. Acta Biochimi Polonica, 48: 199-208.
Chauhan, A.S., Jain, N.K. and Diwan, P. (2009). PAMAM Dendrimers in mice Pre-clinical and behavioural toxicity profile of, proceeding the royal of society. Proc. R. Soc, pp. 466.
Cheng Y, Man N, Xu T, Fu R, Wang X, Wang X and Wen L, (2007). Transdermal delivery of nonsteroidal anti-inflammatory drugs mediated by polyamidoamine [PAMAM] dendrimers, J. Pharm. Sci., 96: 595-602.
Csaba N, Garcia-Fuentes M and Alonso M.J, (2006). The performance of nanocarriers for transmucosal drug delivery, Expert. Opin. Drug Deliv, 3: 463-478.
Daniel Q. McNerny, Pascale R. Leroueil and James R. Baker (2010). Understanding specific and nonspecific toxicities: a requirement for the development of dendrimer-based pharmaceuticals, Advance review, John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol, 2: 249-259
Frechet J.M.J. and D.A. Tomalia, (2001). Introduction to the Dendritic state: Dendrimers and other Dendritic Polymers. John Wiley and Sons Ltd.
Giridhar Thiagarajan, Khaled Greish and Hamidreza Ghandehari (2013). Charge affects the oral toxicity of poly[amidoamine] dendrimers, European Journal of Pharmaceutics and Biopharmaceutics. 84(2): 330-4.
H.N.Patel and Dr. P.M.Patel, (2013). Dendrimer Applications – A Review, Int J Pharm Bio Sci 4: 454-463.
Hawaker, C., K.L. Wooley and J.M.J. Frechet, (1993). Journal of Chemical Society. Perkin Transactions, 1: 1287-1289.
I.B. Erick (2006). Engeineering Dendrimer for Biological Application, Frontiers in chemistry.
Jaeschke, H. Gores, G.J. Cederbaum, A.I, Hinson, J.A. Pessayre, D. and Lemasters J.J., (2002). Mechanisms of hepatotoxicity. Toxicol. Sci. 65: 166-76.
Jevprasesphant R. Penny J. Jalal R. Attwood, D., McKeown, N.B., and A.D Emanuele (2003). The influence of surface modification on the cytotoxicity of PAMAM Dendrimers. Int J Pharm, 252: 263-266.
K. Inoue, (2000) Functional dendrimers, hyperbranched and star polymers, Prog. Polym. Sci. 25: 453-571.
Keerti Jain, Prashant Kesharwani, Umesh Gupta, and N. K. Jain, (2010). Dendrimer toxicity: Let’s meet the challenge, International Journal of Pharmaceutics 394: 122-142.
Kukowska-Latallo JF, Bielinska AU, Johnson J, Spindler R, Tomalia DA, et al. (1996). Efficient transfer of genetic material into mammalian cells using starburst polyamidoamine dendrimers. Proc Natl Acad Sci USA 93: 4897-4902.
Malik N, Wiwattanapatapee R, Klopsch R, Lorenz K, Frey H, et al (2000). Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. J Control Release, 65: 133-148.
Mohammad, N. and D. Antony, (2006). Crossing cellular barriers using dendrimers nanotechnologies. Current Opinion in Pharmacology 6: 522-527.
Nanjwade B.K., Kishore V.S. and Thakare S. A., (2011). Novel Drug Delivery Systems and Regulatory Affairs. IKON BOOKS, Publishers and Distributors, New Delhi, 1-4: 29-33.
P. Sedl´akov´a, J. Svobodov´a, I. Mikˇs´ık a and H. Tom (2006). as Separation of poly[amidoamine] [PAMAM] dendrimer generations by dynamic coating capillary electrophoresis, , Journal of Chromatography B, 841 135–139.
Patel RP et al. (2007). Dendrimers: A new innovation in drug delivery”, Pharma Bio World, 42-52.
Pushkar, S., A. Philip, K. Pathak and D. Pathak (2006). Dendrimers: Nanotechnology Derived Novel Polymers in Drug Delivery. Indian Journal of Pharmaceutical Education and Research, 40: 153-158.
S. Sadekar A.C. and H. Ghandehari, (2012). Transepithelial transport and toxicity of PAMAM dendrimers: Implications for oral drug delivery, Advaned Drug Delivery Reviews 64: 571-588.
Sadekar, S. and Ghandehar,i H., (2012). Transepithelial transport and toxicity of PAMAM Dendrimers Implications for oral drug delivery. Advanced Drug Delivery Reviews, 64: 571–588
Scott H. Medina and Mohamed E. H. El-Sayed*(2009). Dendrimers as Carriers for Delivery of Chemotherapeutic Agents, Chem. Rev. 109: 3141-3157.
Sivabalan, M. and Jeyapragash, R. (2013). Dendrimer: A Novel Polymer. IJRPC, Vol. 3, Issue 2 .
Sonke, S. and Tomalia D.A. (2005). Dendrimers in biomedical application reflection on the field. Advanced Drug Delivery Reviews, 57: 2106-2129.
Srinivasa-Gopalan Sampathkumar, and Kevin J. Yarema, Dendrimers in Cancer Treatment and Diagnosis. Nanotechnologies for the Life Sciences 7: 31387-97.
Tatiana Tocchini Felippotti, ScDa, et.al. (2011). Effect of a nanostructured dendrimer-naloxonazine complex on endogenous opioid peptides μ1 receptor-mediated post-ictal antinociception, Nanomedicine: Nanotechnology, Biology, and Medicine 7(6): 871-880.
Tolia G.T, Choi H.H and Ahsan F (2008). The role of dendrimers in drug delivery, Pharmaceut. Tech 32: 88-98.
Tomalia D. A., Naylor A. M., and. Goddard W. A. (1990). Starburst dendrimers: molecular-level control of size, shape, surface chemistry,topology, and flexibility from atoms to macroscopic 8matter. Angew. Chem. Int. Ed. 29: 138-175.
Tomalia, D.A., (2005). Birth of a new macromolecular architecture Dendrimers as quantized building blocks for nanoscale synthetic polymer chemistr. Prog. Polym. Sci 30: 294-324.
Trivedi, V. Patel, U. Daslaniya, Patel G, Bhiman,i B. Dhiren and Vyas B (2012). Dendrimer Polymer of 21 St Century, Vol. 1, Issue 2.
