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

Int J Pharm. 2010 Oct 15;398(1-2):185-9. doi: 10.1016/j.ijpharm.2010.07.019. Epub 2010 Jul 22.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Dendrimers / administration & dosage
  • Dendrimers / chemistry
  • Dendrimers / pharmacokinetics*
  • Diffusion / drug effects
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics*
  • Methoxsalen / administration & dosage
  • Methoxsalen / chemistry
  • Methoxsalen / pharmacokinetics*
  • Permeability
  • Skin Absorption / physiology*
  • Solubility
  • Swine

Substances

  • Dendrimers
  • Drug Carriers
  • PAMAM Starburst
  • Methoxsalen