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

NOVEL HYDROXYL TERMINATED DENDRIMERS AS POTENTIAL DRUG CARRIERS: SUSTAINED RELEASE, HEMOLYSIS AND CYTOTOXICITY STUDY

Objective: Potential of novel hydroxyl terminated dendrimer generations G1(OH)8, G2(OH)32 and G3(OH)128 as solubility enhancers of model drug ketoprofen was evaluated. G3(OH)128 dendrimer was further explored as the novel carrier for sustained release of ketoprofen. Cytotoxicity and hemolytic potential of G3(OH)128 dendrimer were studied to evaluate toxicity of dendrimer. Methods: Higuchi and Connors method was employed to evaluate improved solubility of ketoprofen at different pH and dendrimer generation. Ketoprofen was loaded into G3(OH)128 dendrimer by inclusion complex method. Ketoprofen loaded dendrimer was characterized by Flourier Transform infrared spectroscopy. Sustained release of ketoprofen from ketoprofen loaded dendrimers was studied and compared to that of free ketoprofen. Cytotoxicity of dendrimers on A-549 cell lines were studied by MTT assay technique. Hemolytic potential of G3 dendrimer was also studied. Results: Solubility of practically insoluble ketoprofen was improved up to 0.77-4.89 mg/ml by dendrimer generations. Solubility of ketoprofen was increased with increase in pH, concentrationand generation number of dendrimer. Ketoprofen was released relatively slowly from ketoprofen loaded dendrimer compared to free ketoprofen. Cytotoxicity and hemolytic assay revealed that dendrimers were less toxic compared to PAMAM dendrimers. Conclusion: Improved solubility of ketoprofen by dendrimer generations, its slow release from G3(OH)128 dendrimer and cytotoxicity and hemolytic assay showed dendrimers have potential as drug carriers. Keywords: Triazine Based Dendrimer, Sustained Release, Cytotoxicity, Hemolysis, Ketoprofen, Encapsulation

ENHANCED SOLUBILITY OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS BY HYDROXYL TERMINATED S-TRIAZINE BASED DENDRIMERS

Objective: To synthesize and characterized s-triazine based dendrimer generations fromN,N'-bis(4,6-dichloro-1,3,5-triazin-2-yl)hexane-1,6-diamine as core. To use dendrimer generation (G1-G3) as solubility enhancers of Ketoprofen, Ibuprofen, and Diflunisal and to study effects of factors such as pH, concentration of dendrimer and generation number on solubility of NSAIDS.Methods: s-triazine based dendrimer was synthesized up to generation 3 by divergent method. Synthesized dendrimer generations were characterized by IR, 1H-NMR, 13C-NMR, ESI-Mass spectrometryand elemental analysis. Candidature of full generation triazine based dendrimers (G1-G3) as solubility enhancers of NSAIDS were investigated by Higuchi and Connors method at different dendrimer concentrations, pH and generations.Results: Dendrimer was synthesized up to generation 3 and structures of dendrimer generations were confirmed by IR, 1H-NMR, 13C-NMR and ESI-Mass spectrometry. Dendrimer significantly enhances solubility of NSAIDS by either hydrophobic interaction or hydrogen bonding or both.Conclusion: Synthesized triazine based dendrimers (G1-G3) enhances solubility of NSAIDs in water. Solubility of NSAIDS increased with increase in concentration of the dendrimer, pH and dendrimer generation.  The order of solubility of NSAIDS was found to be Ketoprofen> Ibuprofen >Diflunisal by dendrimer.Keywords: triazine trichloride, dendrimer, Nonsteroidal Anti-Inflammatory Drugs, solubility enhancer