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

The Age-Dependent Contribution of Aortic Incident and Reflected Pressure Waves to Central Blood Pressure in African-Americans

Aging is associated with increased central aortic systolic pressure (CSP) and pulse pressure which are predictive of cardiovascular events. Mechanisms implicated for higher central pressures include a higher forward incident pressure wave (P1), higher augmented pressure (AP), and shorter reflected wave round trip travel time (Tr). African-Americans (AA) have more frequent and deleterious blood pressure elevation. Using applanation tonometry, we studied the association of age and CSP with P1 and AP in 900 AA subjects. Data showed that in subjects ≤50 years old, CSP was mediated by AP but not P1 or Tr, whereas in those >50, CSP was mediated by both AP and P1 and to a lesser extent by Tr. Predictive models were significant (R2 = 0.97) for both age groups. In conclusion, wave reflection is the primary determinant of CSP in younger AA, while in older subjects, CSP is mediated by both the magnitude and timing of wave reflection as well as aortic impedance

On the Job

<p>DPSCs were exposed to various MG132 or p65 siRNA concentrations (A and B, respectively) and cytokines in the presence of MG132 or p65 siRNA (C and D, respectively) for 7 days. Col(I)-α1 mRNA was assayed using qRT-PCR. Data are presented as the mean ± S. E. M. of triplicate measures from triplicate experiments. Symbols: Asterisks (*) indicate statistical comparison with control result; plus signs (+) indicate statistical comparison with IL-1β (0.5 ng/ml) and TNFα (1.0 ng/ml) treatment (low cytokine dose); triangle (Δ) indicates statistical comparison with IL-1β (10.0 ng/ml) and TNFα (20.0 ng/ml) treatment (high cytokine dose). Statistical comparison was made using ANOVA testing with Dunnett’s posthoc analysis. Statistical significance was represented by *, +, or Δ for <i>p</i> < 0.05; **, ++, or ΔΔ for p < 0.01; ***, +++, or ΔΔΔ for p < 0.001.</p

Decreasing NF-κB Expression Enhances Odontoblastic Differentiation and Collagen Expression in Dental Pulp Stem Cells Exposed to Inflammatory Cytokines

Inflammatory response in the dental pulp can alter the collagen matrix formation by dental pulp stem cells and lead to a delay or poor healing of the pulp. This inflammatory response is mediated by cytokines, including interleukin-1β and tumor necrosis factor-α. In this study, it is hypothesized that suppressing the actions of these inflammatory cytokines by knocking down the activity of transcription factor Nuclear Factor–κB will lead to dental pulp stem cell differentiation into odontoblasts and the production of collagen. Here, the role of Nuclear Factor–κB signaling and its reduction was examined during odontogenic behavior in the presence of these cytokines. The results showed a significant increase in Nuclear Factor–κB gene expression and p65 protein expression by interleukin-1β and tumor necrosis factor-α. Nuclear Factor–κB activation in the presence of these cytokines decreased significantly in a dose-dependent manner by a Nuclear Factor–κB inhibitor (MG132) and p65 siRNA. Down-regulation of Nuclear Factor–κB activity also enhanced the gene expression of the odontoblastic markers (dentin sialophosphoprotein, Nestin, and alkaline phosphatase) and displayed an odontoblastic cell morphology indicating the promotion of odontogenic differentiation of dental pulp stem cells. Finally, dental pulp stem cells exposed to reduced Nuclear Factor–κB activity resulted in a significant increase in collagen (I)-α1 expression in the presence of these cytokines. In conclusion, a decrease in Nuclear Factor-κB in dental pulp stem cells in the presence of inflammatory cytokines enhanced odontoblastic differentiation and collagen matrix formation.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund

Dendritic macromolecules as nano-scale drug carriers: Phase solubility, in vitro drug release, hemolysis and cytotoxicity study

Potential of nanoscale triazine based dendritic macromolecules G1, G2 and G3 as solubility enhancers of drug was investigated. Effect of pH, concentration and generation of synthesized dendritic macromolecules on solubility of ketoprofen was studied. G3 dendrimer was further exploited as carrier for sustained release. Ketoprofen was encapsulated by inclusion complex method and also characterized by Flourier Transform Infrared spectroscopy. Sustained release study of ketoprofen from ketoprofen loaded dendrimer was carried out and compared with free ketoprofen. Hemolytic potential and Cytotoxicity assay using A-549 lung cancer cell lines revealed that synthesized triazine based dendritic macromolecules having more potential that commercially available PAMAM dendrimer

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&gt; Ibuprofen &gt;Diflunisal by dendrimer.Keywords: triazine trichloride, dendrimer, Nonsteroidal Anti-Inflammatory Drugs, solubility enhancer