EFFECT OF BENZALKONIUM CHLORIDE ON PERCUTANEOUS-ABSORPTION OF ANTISENSE PHOSPHOROTHIOATE OLIGONUCLEOTIDES

The effect of benzalkonium chloride on skin permeability of partially modified antisense phosphorothioate oligonucleotides (PS-ODN), which a re designed as scar formation inhibitor, was investigated using Franz Diffusion Cell. When the concentration ratio of PS-ODN-quarternary amm onium salt complex is more than 1:100, the apparent partition coeffici ent (APC) of each complex was increased in the following order; tetrap henyl phosphonium chloride (TPP)< cetyltrimethyl ammonium bromide(CTAB ) < benzalkonium chloride (BZ). The permeability of PS-ODN through the rat skin increased in the presence of BZ. The fluxs of PS-ODN with BZ were increased by addition of Pluronic F 68 or Triton X-100 to phosph ate buffered saline (PBS), respectively. When the mole ratio of PS-ODN to BZ is 1:10, the furs penetrated of PS-ODN with BZ was greatest. Th e increase of the permeability in the presence of BZ might be due to t he formation of lipophilic ion-pair complex between PS-ODN and BZ. By regulation of mole ratio of PS-ODN to BZ, the development of topical d osage forms using PS-ODN as scar formation inhibitor will be possible with minimal systemic exposure.