단백질 약물 방출속도에 미치는 친수성 첨가제의 영향

Effects of Hydrophilic Additives on the Release Rate of Protein Drugs

  • 권영관 (서울대학교 화학생물공학부) ;
  • 김지현 (동국대학교 생명화학공학과) ;
  • 유영제 (서울대학교 화학생물공학부)
  • Kwon, Young-Kwan (School of Chemical and Biological Engineering, Seoul National University) ;
  • Kim, Ji-Hyeon (Department of Chemical and Biochemical Engineering, Dongguk University) ;
  • Yoo, Young-Je (School of Chemical and Biological Engineering, Seoul National University)
  • 발행 : 2007.08.30

초록

첨가제가 단백질 약물 방출 속도 및 약물 제제 제조 및 구조에 미치는 영향을 고찰하였다. 친수성 첨가제인 D-sorbitol의 경우 친유성 첨가제보다 단백질 약물 방출 속도를 감소시킬 수 있었으며 최적의 농도는 3% (w/v)로 나타났다. 또한 제제 제조시 점도를 낮게 유지할 뿐 아니라 상분리 없는 균일한 pluronic 용액상태를 유지하여 약물이 첨가될 경우에 균일한 약물제제를 만들 수 있었다. 한편 D-sorbitol은 pluronic 수용액의 CMC를 낮추고 마이셀 표면에 작용하여 구조를 강화하는 역할을 수행하는 것으로 보인다. 따라서 pluronic 제제에 D-sorbitol을 첨가하여 단백질 약물의 안정성을 향상시키고 효과적인 약물전달 시스템을 설계할 수 있었다.

It has been reported that hydrophobic additives generally decrease the release rate of protein drugs from drug delivery systems (DDS) and hydrophilic additives increase the release rate. In many cases, however, the addition of hydrophilic molecule is necessary for improving the stability of protein drugs. In the present work, the effects of hydrophilic additives on the release profiles, and micelle formation of protein drug formulations were investigated to develop a novel method for protein drug delivery. For model protein drug, bovine serum albumin (BSA) was employed and several hydrophilic additives were used in the release experiments. Hydrophilic additive D-sorbitol showed the lower release rates of BSA than other hydrophobic additives due to the gel strengthening ability of the additive and the optimum concentration of D-sorbitol was 3 w/v % for the retarded release rate. In addition, it was found that the addition of D-sorbitol was very effective for obtaining homogeneous and stable DDS. The results were discussed in terms of the micelle formation and the micelle structure, i.e., the differences in gel structure and the distribution of drugs in micelles.

키워드

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