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

PAMAM dendrimers form host-guest complexes with 8-methoxypsoralene (8-MOP) - the photosensitizer for PUVA therapy. The stoichiometry of complexes was studied by (1)H 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. Copyright 2010 Elsevier B.V. All rights reserved.