New-generation Jeffamine® D230 core amine, TRIS and carboxyl-terminated PAMAM dendrimers: Synthesis, characterization and the solubility application for a model NSAID drug Ibuprofen

Abstract

Many therapeutically active drugs are poor water soluble and, therefore, bioavailability of these molecules in the living cells is low and a major problem. In this study, new-generation Jeffamine (R) D230 core, amine (NH2), Tris(hydroxymethyl) aminomethane (TRIS), and carboxyl (COOH) terminated poly(amidoamine) PAMAM dendrimers (PAMAMs) were synthesized. Synthesized new-generation PAMAMs were characterized by H-1 NMR, C-13 NMR, ATR-FTIR, and investigated as solubility enhancer of a sample non-steroidal anti-inflammatory drug (NSAID) Ibuprofen (IBU). The effect of generation size (D2-D4), concentration (0-2.0 mM), and surface functional group (NH2, COOH, TRIS) of the synthesized new-generation PAMAMs on the aqueous solubility of IBU was also investigated. The observed solubility enhancement of IBU was in the order of D4.COOH (18.21 mg/mL)> D3.COOH (13.21 mg/mL)> D4.TRIS (10.30 mg/mL)> D2.COOH (8.55 mg/mL)> D3.TRIS (6.04 mg/mL)> D4.NH2 (4.56 mg/mL)> D3.NH2 (3.36 mg/mL)> D2.TRIS (2.42 mg/mL)> D2.NH2 (1.86 mg/mL). Results showed that synthesized PAMAMs improved the solubility of IBU significantly (30 to 247-fold) with an increasing generation size, and concentration.