Design of triptorelin loaded nanospheres for transdermal iontophoretic administration

Triptorelin is a decapeptide analog of luteinizing hormone releasing hormon e. currently used for the treatment of sex-hormones dependents diseases. Th e aim of this work was to Prepare triptorelin-loaded nanospheres useful for transdermal iontophoretic administration. Nanospheres were prepared with t he double emulsion/solvent evaporation technique. The effect of three param eters on the encapsulation efficiency has been determined: the role of the PH of the internal acid external aqueous phases. the nature of the organic solvent and the effect of three different poly(lactide-co-glycolide) (PLGA) co-polymers. Particle size, zeta Potential and release kinetics were also determined. The encapsulation efficiency varied from 4 to 83% reaching the maximum value when both the internal and the external water phases were bro ught to PH 7 (isoelectric point of the peptide), methylene chloride was use d as solvent of the copolymers and PLGA rich in free carboxylic groups was employed. The release profiles obtained with this co-polymer were character ized by the absence of burst effect. This behavior as well as the high enca psulation efficiency was explained by an ionic interaction occurring betwee n the Peptide and the co-polymer. This supports the already expressed theor y that the release of peptides and proteins from PLGA nanospheres is also g overned by the affinity of the encapsulated molecule versus the polymer. Th e obtained nanoparticles. regarding their size. amount encapsulated and zet a potential, were shown to be suitable for transdermal iontophoretic admini stration. (C) 2001 Elsevier Science B.V. All rights reserved.