PAMAM dendrimers as solubilizers and hosts for 8-methoxypsoralene enabling transdermal diffusion of the guest

Abstract

PAMAM dendrimers form host–guest complexes with 8-methoxypsoralene (8-MOP) – the photosensitizer for PUVA therapy. The stoichiometry of complexes was studied by 1H NMR spectroscopy in solution and by differential scanning calorimetry in neat mixtures containing 8-MOP and dendrimers of generations G2.5, G3, G3.5, and G4. The dendrimers showed solubilization effect for 8-MOP resulting in increase of 8-MOP concentration in methanol up to 15 molecules of 8-MOP per G2.5 and G3 and 30 molecules of 8-MOP per G3.5, and G4. Isolation of oily host–guest complexes containing 3 or 7 molecules of 8-MOP per G3 and G4, respectively corroborate well with DSC results; glass transition temperature of neat host–guest complexes increases with number of host molecules in comparison with G3 or G4, until the capacity of host is exceeded. The oily host–guest complexes of stoichiometry 3:1 and 7:1 of 8-MOP to G3 and G4, respectively are well soluble in water. The 3:1 host–guest complexes diffused slowly through polyvinyldifluoride and pig ear skin membranes, when released from o/w emulsion. The host–guest complex 8-MOP- G3 was proposed as convenient formulation for psoralene skin administration in PUVA therapy.