Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
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Effect of Benzalkonium Chloride on Percutaneous Absoption of Antisense Phosphorothioate Oligonucleotides

  • Lee, Young-Mi (College of Pharmacy and Medicinal Resource Research Center, Wonkwang University) ;
  • Lee, Sung-Hee (College of Pharmacy and Medicinal Resource Research Center, Wonkwang University) ;
  • Ko, Geon-Il (College of Pharmacy and Medicinal Resource Research Center, Wonkwang University) ;
  • Kim, Jae-Baek (College of Pharmacy and Medicinal Resource Research Center, Wonkwang University) ;
  • Sohn, Dong-Hwan (College of Pharmacy and Medicinal Resource Research Center, Wonkwang University)
  • Published : 1996.12.01
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Abstract

The effect of benzalkonium chloride on skin permeability of partially modified antisense phosphorothioate oligonucleotides (PS-ODN), which are designed as scar formation inhibitor, was investigated using Franz Diffusion Cell. When the concentration ratio of PS-ODN-quarternary ammonium salt complex is more than 1:100, the apparent partition coefficient (APC) of each complex was increased in the following order; tetraphenyl 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 phosphate buffered saline (PBS), respectively. When the mole ratio of PS-ODN to BZ is 1:10, the fluxs penetrated of PS-ODN with BZ was greatest. The increase of the permeability in the presence of BZ might be due to the 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 dosage forms using PS-ODN as scar formation inhibitor will be possible with minimal systemic exposure.

Keywords

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