Spectroscopic and calorimetric studies of formation of the supramolecular complexes of PAMAM G5-NH₂ and G5-OH dendrimers with 5-fluorouracil in aqueous solution

Adam Buczkowski; Tomasz Olesinski; Elzbieta Zbicinska; Pawel Urbaniak; Bartlomiej Palecz

doi:10.1016/j.ijpharm.2015.05.033

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. 2015 Jul 25;490(1-2):102-11. doi: 10.1016/j.ijpharm.2015.05.033. Epub 2015 May 18.

Authors

Adam Buczkowski¹, Tomasz Olesinski², Elzbieta Zbicinska³, Pawel Urbaniak⁴, Bartlomiej Palecz²

Affiliations

¹ Unit of Biophysical Chemistry, Department of Physical Chemistry, Faculty of Chemistry, University of Lodz, Pomorska 165, 90-236 Lodz, Poland. Electronic address: [email protected].
² Unit of Biophysical Chemistry, Department of Physical Chemistry, Faculty of Chemistry, University of Lodz, Pomorska 165, 90-236 Lodz, Poland.
³ Molecular Spectroscopy Laboratory, Faculty of Chemistry, University of Lodz, Tamka 12, 91-403 Lodz, Poland.
⁴ Department of Inorganic and Analytical Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12, 91-403 Lodz, Poland.

PMID: 25997661
DOI: 10.1016/j.ijpharm.2015.05.033

Abstract

The results of spectroscopic measurements (increase in solubility, equilibrium dialysis, (1)H NMR titration) and calorimetric measurements (isothermal titration ITC) indicate exothermic (ΔH<0) and spontaneous (ΔG < 0) combination of an antitumor drug, 5-fluorouracil, by both cationic PAMAM G5-NH2 dendrimer and its hydroxyl analog PAMAM G5-OH in aqueous solutions at room temperature. PAMAM G5-NH2 dendrimer combines about 70 molecules of the drug with equilibrium constant K ≅ 300, which is accompanied by an increase in the system order (ΔS < 0). Hydroxyl dendrimer, PAMAM G5-OH, combines about 14 molecules of 5-fluorouracil with equilibrium constant K ≅ 100. This process is accompanied by an increase in the system disorder (ΔS > 0).

Keywords: 5-Fluorouracil; Dendrimer; Equilibrium dialysis; Isothermal titration calorimetry; PAMAM G5-NH(2); PAMAM G5-OH.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Calorimetry / methods
Chemistry, Pharmaceutical / methods
Dendrimers / chemistry*
Fluorouracil / chemistry*
Magnetic Resonance Spectroscopy / methods
Molecular Structure
Pharmaceutical Solutions / chemistry*
Solubility
Water / chemistry*

Substances

Dendrimers
PAMAM Starburst
Pharmaceutical Solutions
Water
Fluorouracil