Development and characterization of triazine based dendrimers for delivery of antitumor agent.
In the present study we developed the novel kind of triazine dendrimers by utilizing differential reactivity of the cyanuric chloride (triazine trichloride) which overcome the limitations associated with the others classes of dendrimers like toxicity, low yield, high synthesis cost etc. Triazine dendrimers were synthesized by divergent method using triazine trichloride as core and diethanolamine as branching unit to avoid the use of protecting group and functional group interconversion up to third generation. These hydroxyl terminated dendrimers were characterized by FTIR, 1HNMR, 13CNMR, ES mass spectroscopy, and by elemental analysis. The yield of pure G3 dendrimers was 63%. This novel dendrimers increases the aqueous solubility of hydrophobic drug Paclitaxel up to 0.562 mg/ml as well as showed control release behavior. Hemolytic and toxicology studies of this dendrimer in mice showed no adverse toxicity to the kidneys and the liver up to 200 mg/kg dose (i.p). Triazine being a hydrophobic compound, the core of this dendrimer is hydrophobic and supposed to easily incorporate the hydrophobic guest while presence of hydroxyl group on periphery increases its water solubility and reduces its toxicity; and thus it is useful in various fields like gene delivery, MRI contrasting agents, vaccines or as solubilization tool.
Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar, M.P. 470003, India.
Kuldeep K
KK
Bansal
Deepak
D
Kakde
Umesh
U
Gupta
Narendra K
NK
Jain
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001806:Blood Urea Nitrogen; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D016503:Drug Delivery Systems / Q000379:methods*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008807:Mice, Inbred BALB C; D019906:Nuclear Magnetic Resonance, Biomolecular; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
D000970:Antineoplastic Agents; D050091:Dendrimers; D014227:Triazines; D000410:Alanine Transaminase; D017239:Paclitaxel