An Alternative Approach for Acetylation of Amine Terminated Polyamidoamine (PAMAM) Dendrimer

Authors

  • Surya Prakash Gautam Department of Pharmaceutics, CT Institute of Pharmaceutical Sciences, Jalandhar, Punjab
  • Raj K. Keservani School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal (M.P.)
  • Tapsya Gautam Smriti College of Pharmaceutical Education
  • Arun K. Gupta Smriti College of Pharmaceutical Education
  • Anil Kumar Sharma Department of Pharmaceutics, CT Institute of Pharmaceutical Sciences, Jalandhar, Punjab

Keywords:

Dendrimers, Polyamidoamine (PAMAM), Etylenediamine, Acetylation, Linker, Surface Properties

Abstract

Aim. Polyamidoamine (PAMAM) dendrimers inherent properties have made it the nanocarrier of choice in the current era of innovation. Dendrimer based products are growing and mushrooming like anything in the current time. Although it suffer from hemolytic toxicity which could be reduced by protecting free amino group.

Methods. In the present work alternate acetylated method for PAMAM dendrimers was discussed. 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide Linker was used for acetylation. The acetylated conjugate was evaluated for color reaction, Ultraviolet–visible spectroscopy, Fourier Transform infrared spectroscopy, Differential scanning calorimetric, Nuclear magnetic resonance spectra studies.

Results. The PAMAM dendrimers were synthesized using divergent approach and further acetylated. Change in λmax values from 282.0 to 282.5 nm was observed for acetylated dendrimers. Characteristic peak of N-H stretch of primary amine at 3284.16 cm-1 was disappeared due to conversion of primary amine to secondary amine. A new peak of –(CO)-NH stretch was obtained at 1640.28 cm-1 (medium) which shows attachment of acetic acid surface group. The changes in Endothermic peak from 120.56 to 110.400C were observed which shows the PAMAM dendrimers surface modifications The peak of –NH2 at 2.99 ppm was replaced by (–NHCOCH3) at 2.42 ppm further supports the proof of acetylation.

Conclusions. The spectral data clearly revealed that this approach for acetylation gives considerable amount of acetylation in less time duration with elimination of organic solvent. This method could be employed for regular acetylation of amine terminated nanocarriers. EDC linker mediated capping of amine groups opened a new avenue for acetylation of amine terminated protein/peptides.

Downloads

Download data is not yet available.

References

Garg T, Singh O, Saahil A, Murthy RSR. Dendrimers-A novel scaffold for drug delivery. Intl. J. Pharm. Sci. Rev. Res. 2001; 7: 211-220.

Konda SD, Aref M, Wang S, Brechbiel M, Wiener EC. Specific targeting of folate-dendrimer MRI contrast agents to the high affinityfolate receptor expressed in ovarian tumor xenografts. MAGMA. 2001; 12 (2-3): 104-113.

Namazi H, Adeli M. Dendrimers of citric acid and poly (ethylene glycol) as the new drug- delivery agents. Biomaterials. 2005; 26: 1175-1183.

Patri AK, Kukowska-Latallo JF, Baker 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: 220322-14.

Zeng F, Zimmerman SC. Dendrimers in supramolecular chemistry: From molecular recognition to self-assembly. Chem. Rev. 1997; 97 (5): 1681-1712.

Purohit G, Sakthivel T, Florence AT. Interaction of cationic partial dendrimers with charged and neutral liposomes. Intl. J Pharm. 2001; 214: 71-76.

Yellepeddi VK, Kumar A, Palakurthi S. Surface modified poly(amido)amine dendrimers as diverse nanomolecules for biomedical applications. Exp. Opin. Drug Deliv. 2009; 6 (8): 835-850.

Majoros IJ, Keszler B, Woehler S, Bull T, Baker JR. Acetylation of poly(amido)amine dendrimers. Macromolecules. 2003; 36: 5526-5529.

Kolhatkar RB, Kitchens KM, Swaan PW, Ghandehari H. Surface acetylation of poly(Amidoamine) (PAMAM) dendrimers decrease cytotoxicity while maintaining membrane permeability. Bioconjugate. Chem. 2007; 18 (6): 2054-2060.

Waite CL, Sparks SM, Uhrich KE, Roth CM. Acetylation of PAMAM dendrimers for cellular delivery of siRNA. BMC Biotechnology. 2009; 9: 38 doi:10.1186/1472-6750-9-38

Jevprasesphant R, Penny J, Jalal R, Attwood D, McKeown NB, D’Emanuele A. The influence of surface modification on the cytotoxicity of PAMAM dendrimers. Intl. J. Pharm. 2003; 252: 263-266.

Kim T, Seo HJ, Choi JS, Jang HS, Baek JU, Kim K, Park JS. PAMAM-PEG-PAMAM: novel triblock copolymer as a biocompatible and efficient gene delivery carrier. Biomacromolecules. 2004; 5: 2487-2492.

Forrest ML, Meister G, Koerber J, Pack D. Partial acetylation of polyethylenimine enhances in vitro gene delivery. Pharm. Res. 2004; 21: 365-371.

Gabrielson NP, Pack DW. Acetylation of polyethylenimine enhances gene delivery via weakened polymer/DNA interactions. Biomacromolecules. 2006; 7: 2427-2435.

Sharma A, Gautam SP, Gupta AK. Surface modified dendrimers: Synthesis and characterization for cancer targeted drug delivery. Bioorg. Med. Chem. 2011; 19: 3341-3346.

Khambete H, Gautam SP, Karthikeyan C, Ramteke S, Moorthy NSHN, Trivedi P.A new approach for PEGylation of dendrimers. Bioorg. Med. Chem. Lett. 2010; 20: 4279-4281.

Gautam SP, Gupta AK, Sharma A, Gautam T. Synthesis and analytical characterization of ester and amine terminated PAMAM dendrimers. Global J Med. Res. Pharma, Drug Dis. Toxicol. Med. 2013; 13(3): 7-15.

Erk N. Application of first derivative UV-spectrophotometry and ratio derivative spectrophotometry for the simultaneous determination of candesartan cilexetil and hydrochlorothiazide. Phmz. 2003; 58(11): 796-800.

Ronald CH, Bauer BJ, Paul SA, Franziska G, Eric A. Templating of inorganic nanoparticles by PAMAM/PEG dendrimer–star polymers. Polymer. 2002; 43:5473–5481.

Lajos PB, Ganser RT, Xiangyang S. Characterization of dendrimer-gold nanocomposite materials. Mater. Res. Soc. Symp. Proc, 2005; 847.

Pesak DJ, Moore JS. Columnar liquid crystals from shape persistent dendritic molecules, Angew. Chem. Int. Ed. Engl. 1999; 36: 1636–1639.

Gardikis K, Hatziantoniou S, Viras K, Wagner M, Demetzos C. A DSC and raman spectroscopy study on the effect of PAMAM dendrimer on DPPC model lipid membranes, Intl. J. Pharm. 2006; 318: 118-123.

Victoria M, Guerra J, Aldrik H, Richard M. NMR Characterization of Fourth-Generation PAMAM dendrimers in the presence and absence of palladium dendrimer-encapsulated nanoparticles. J. Am. Chem. Soc. 2009; 131:341–350.

Karlos X, Simanek E. Conformational analysis of triazine dendrimers: Using NMR spectroscopy to probe the choreography of a dendrimer’s dance. Macromol. 2008; 41: 4108–4114.

Downloads

Published

2015-09-20

How to Cite

1.
Gautam SP, Keservani RK, Gautam T, Gupta AK, Sharma AK. An Alternative Approach for Acetylation of Amine Terminated Polyamidoamine (PAMAM) Dendrimer. Ars Pharm [Internet]. 2015 Sep. 20 [cited 2024 Jul. 22];56(3):155-9. Available from: https://revistaseug.ugr.es/index.php/ars/article/view/3434

Issue

Vol. 56 No. 3 (2015)

Section

Original Articles

License

The articles, which are published in this journal, are subject to the following terms in relation to the rights of patrimonial or exploitation:

  1. The authors will keep their copyright and guarantee to the journal the right of first publication of their work, which will be distributed with a Creative Commons BY-NC-SA 4.0 license that allows third parties to reuse the work whenever its author, quote the original source and do not make commercial use of it.

b. The authors may adopt other non-exclusive licensing agreements for the distribution of the published version of the work (e.g., deposit it in an institutional telematic file or publish it in a monographic volume) provided that the original source of its publication is indicated.

c. Authors are allowed and advised to disseminate their work through the Internet (e.g. in institutional repositories or on their website) before and during the submission process, which can produce interesting exchanges and increase citations of the published work. (See The effect of open access).