Thermodynamic interaction between PAMAM G4-NH2, G4-OH, G3.5-COONa dendrimers and gemcitabine in water sotutions

Abstract

The thermodynamics of complex formation of polyamideamine dendrimers: cationic PAMAM G4-NH2, neutral PAMAM G4-OH and anionic PAMAM G3.5-COONa with gemcitabine hydrochloride, an antitumor drug, in water at a temperature of 250C was studied. The investigations were carried out with the use of ITC measurements allowing one to determine the number of the drug molecules bonded by the dendrimer macromolecule, the equilibrium constants of the complex formed and the values of enthalpy and entropy of their formation. The measurements results obtained show different numbers of the drug molecules bonded by dendrimer macromolecules depending on the properties of their terminal groups.

Keywords

• PAMAM dendrimers G-4
• gemcitabine hydrochloride
• isothermal titration calorimetry

References

1. Buczkowski, A., Olesinski, T., Zbicinska, E., Urbaniak, P., & Palecz , B. (2015). Spectroscopic and calorimetric studies of formation of the supramolecular complexes of PAMAM G5-NH2 and G5-OH dendrimers with 5-fluorouracil in aqueous solution. Int J Pharm., 490, 102-111.
2. Buczkowski, A., & Palecz, B. (2014). Study of the interactions of PAMAM-NH2 G4 dendrimer with selected natural amino acids in aqueous solutions. J. Chem. Thermodyn., 70, 95-100.
3. Buczkowski, A., Sekowski, S., Grala, A., Palecz, D., Milowska, K., Urbaniak, P., et al. (2011). Interaction between PAMAM-NH2 G4 dendrimer and 5-fluorouracil in aqueous solution. Int J Pharm., 408, 266-270.
4. Buczkowski, A., Urbaniak, P., & Palecz, B. (2012). Thermochemical and spectroscopic studies on the supramolecular complex of PAMAM-NH2 G4 dendrimer and 5- fluorouracil in aqueous solution. Int J Pharm., 428, 178– 182.
5. Buczkowski, A., Urbaniak, P., & Palecz, B. (2013). Interaction between PAMAM-NH2 G4 dendrimer and paracetamol in aqueous solution. J. Mol. Liq., 186, 70-75.
6. Kanchi, S., Suresh, G., Priyakumar, U. D., Ayappa, K. G., & Maiti, P. K. (2015). Molecular dynamics study of the structure, flexibility, and hydrophilicity of PETIM dendrimers: a comparison with PAMAM dendrimers. Journal of Physical Chemistry B, 119, 12990- 13001.
7. Kesharwani, P., Jain, K., & Jain, N. K. (2014). Dendrimer as nanocarrier for drug delivery. Prog. Polym. Sci., 39, 268-307. Medina, S. H., & El-Sayed, M. E. H. (2009). Dendrimers as carriers for delivery of chemotherapeutic agents. Chem. Rev., 109, 3141–3157.
8. Niu, Y., Sun, L., & Crooks, R. M. (2003). Determination of the intrinsic proton binding constants for poly(amidoamine) dendrimers via potentiometric pH titration. Macromolecules, 36, 5725-5731.

9. Vlahov, I. R., & Leamon, C. P. (2012). Engineering folate-drug conjugates to target cancer: from chemistry to clinic. Bioconjugate Chemistry, 23, 1357-1369.
10. Yavuz, B., Pehlivan, S. B., Vural, I., & Ünlü, N. (2015). In Vitro/In Vivo Evaluation of Dexamethasone - PAMAM Dendrimer Complexes for Retinal Drug Delivery. J. Pharm. Sci., 104, 3814-3823