A NANOSCALE DENDRITIC MACROMOLECULES BASED ON ETHANE 1,2-DIAMINE AS POTENTIAL DRUG CARRIERS FOR NSAIDS: SYNTHESIS, CHARACTERIZATION AND APPLICATIONS
Objective: The present work deals with the objective of development and characterization of novel dendritic macromolecules as solubility enhancer and carrier for sustained release of Ketoprofen. Cytotoxicity and hemolytic assay of dendritic macromolecules were also estimated as an objective to evaluate its toxicity and biocompatibility.
Methods: Dendritic macromolecules were synthesized using divergent method. Synthesized macromolecules were characterized by spectral techniques such as FTIR, 1H-NMR, 13C-NMR electro-spray ionization mass spectrometry and elemental analysis. Enhanced aqueous solubility of ketoprofen was evaluated with respect to pH, generation number and concentration of dendrimer using Higuchi and Connors method. Sustained release of ketoprofen from ketoprofen loaded dendrimers was measured and compared with that of free ketoprofen. Hemolytic assay and cytotoxicity of G3 dendrimer on A-549 cell lines were studied to evaluate toxicity and biocompatibility of dendrimer. All dendritic macromolecules were fully characterized by spectral techniques.
Results: Solubility study revealed that aqueous solubility of ketoprofen by dendrimer increased with increase in pH, concentration and generation of dendrimer. Ketoprofen was released slowly from ketoprofen loaded dendrimer compared to that of free ketoprofen. Dendritic macromolecules were less cytotoxic and showed less hemolytic potential.
Conclusion: It can be concluded that dendrimer have high potential as carriers and solubility enhancers of hydrophobic drug.Keywords: Triazine based dendrimer, Ketoprofen, Drug Carrier, Cytotoxicity, Hemolysis.
2. Patel R, Patel H, Gajjar D, Patel PM. Enhanced solubility of non-steroidal anti-inflammatory drugs by hydroxyl terminated S-Triazine based dendrimers. Asian J Pharm Clin Res 2014;7:156-61.
3. Cheng Y, Xu Z, Ma M, Xu T. Dendrimers as drug carriers: applications in different routes of drug administration. J Pharm Sci 2008;97:123-43.
4. Gillies ER, Frechet JMJ. Dendrimers and dendritic polymers in drug delivery. Drug Discovery Today 2005;10:35â€“43.
5. Murthy RSR, Garg T, Singh O, Arora S. Dendrimer-a novel scaffold for drug delivery. Int J Pharm Sci Rev Res 2011;7:211-20.
6. Scott RWJ, Wilson OM, Crooks RM. Synthesis, Characterization, and applications of dendrimer-encapsulated nanoparticles. J Phys Chem B 2005;109:692-704.
7. Dufes C, Uchegbu IF, Schatzlein AG. Dendrimers in gene delivery. Adv Drug Delivery Rev 2005:57:2177â€“202.
8. Duan S, Kouketsu T, Kazama S, Yamada K. Development of PAMAM dendrimer composite membranes for CO2 separation. J Membr Sci 2006;283:2-6.
9. Wolinsky JB, Grinstaff MW. Therapeutic and diagnostic applications of dendrimers for cancer treatment. Adv Drug Delivery Rev 2008;60:1037-55.
10. Reek JNH, Arevalo S, Heerbeek RV, Kamer PCJ, van Leeuwen PWNM. Dendrimers in catalysis. Adv Catal 2006;49:71-151.
11. Tomalia DA, Baker H, Dewald J, Hall M, Kallos G, Martin S, et al. A new class of polymers: starburst-dendritic macromolecules. Polym J 1985;17:117â€“32.
12. Hawker CJ, Frechet JMJ. Preparation of polymers with controlled molecular architecture. a new convergent approach to dendritic macromolecules. J Am Chem Soc 1990;112:7638â€“47.
13. Gajjar D, Patel R, Patel H, Patel PM. Triazine based dendrimer as solubility enhancers of ketoprofen: effect of concentration, pH and Generation. Int J Pharm Pharm Sci 2014;6:357-61.
14. Gajjar D, Patel R, Patel H, Patel PM. Removal of heavy metal ions from water by Hydroxyl terminated Triazine-based dendrimer. Desalin Water Treat 2015;55:1209-19.
15. Gajjar D, Patel R, Patel H, Patel PM. Designing of triazine based dendrimer and its application in removal of heavy metal ions from water. Chem Sci Trans 2014;3:897-908.
16. Bansal K, Kakde D, Gupta U, Jain NK. Development, Characterization and triazine based dendrimers for delivery of antitumor agent. J Nanosci Nanotechnol 2010;10:8395â€“404.
17. Gajjar D, Patel R, Patel H, Patel PM. Designing, characterization, and thermal behavior of triazine-based dendrimers. J Polym Eng Sci 2015;35:41-52.
18. Gupta U, Aghashe HB, Asthana A, Jin NK. Dendrimers: novel polymeric nanoarchitectures for solubility enhancement. Biomacromolecules 2006;7:649-58.
19. Yalkowsky S. Techniques of solubilization of drugs. New York: Marcher Dekker; 1981. p. 52.
20. Karkan M, Li L, Muller RH. Overcoming the challenge of poor drug solubility. Pharm Eng 2012;32:1-7.
21. Stegemann S, Leveiller F, Franchi D, de Jong H, Linden H. When poor solubility becomes an issue: from early stage to proof of concept. Eur J Pharm Sci 2007;31:249-61.
22. Higuchi T, Connors A. Phase-solubility techniques. In: Advances in analytical chemistry and instrumentation. New York: John Wiley; 1965. p. 117-212.
23. Na M, Yiyun C, Tongwen X, Yang D, Xiaomin W, Zhenwei L, et al. Dendrimers as potential drug carriers. Part II. Prolonged delivery of ketoprofen by in vitro and in vivo studies. Eur J Med Chem 2006;41:670-4.
24. Gajjar D, Patel R, Patel V, Patel PM. Novel hydroxyl terminated dendrimers as potential drug carriers: sustained release, Hemolysis and cytotoxicity study. Int J Appl Pharm 2015;7:5-9.
25. Patel PM, Patel R, Wadia D, Patel RM. Dendritic macromolecules as nano-scale drug carriers: Phase solubility, in vitro drug release, hemolysis and cytotoxicity study. Asian J Pharm Sci 2015;10:306-13.
26. Duncan R, Izzo L. Dendrimer biocompatibility and toxicity. Adv Drug Delivery Rev 2005;57:2215-37.
27. Domanski DM, Klajnert B, Bryszewska M. Influence of PAMAM dendrimers on human red blood cells. Bioelectrochem 2004;63:189-91