화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Polymer(Korea), Vol.44, No.6, 817-826, November, 2020
DOI10.7317/pk.2020.44.6.817  Export Citation
방광 내 주입용 폴록사머 407 하이드로젤 제형의 고분자 첨가제 스크리닝: 기계적 성질, 젤 형성 능력 및 약물 방출 평가
Screening of Polymer Additives in Poloxamer 407 Hydrogel Formulations for Intravesical Instillation: Evaluation of Mechanical Properties, Gel-forming Capacity, and Drug Release
양희망, 원용훈, 윤호엽, 김창현, 구윤태, 장인호1, 최영욱†
  • 중앙대학교 약학대학
  • 1중앙대학교 의과대학
Hee Mang Yang, Yong Hoon Won, Ho Yub Yoon, Chang Hyun Kim, Yoon Tae Goo, In Ho Chang1, and Young Wook Choi†
  • College of Pharmacy, Chung-Ang University, 84 Heuksuk-ro, Dongjak-gu, Seoul 06974, Korea
  • 1College of Medicine, Chung-Ang University, 84, Heuksuk-ro, Dongjak-gu, Seoul 06974, Korea
E-mail:
초록
폴록사머 407(PLX) 하이드로젤은 방광 내 주입을 위한 전달 시스템으로 사용되고 있지만, 젤의 강도가 충분하지 않다는 한계가 있다. 하이드로젤의 점도 및 강도를 조절하기 위해, 다양한 고분자 첨가제를 선별하였다. 점도의 변화는 고분자량 히알루론산(HHA; 33.524 Pa·s) > 히드록시프로필메틸셀룰로스 > 키토산 > 저분자량 HA > 알긴산 > 카보폴(24.332 Pa·s) 순서로 관찰되었다. 고분자 첨가는 PLX 하이드로젤의 열 가역적 특성을 변화시키지 않았으며, 젤화 온도(21.0-25.3 °C) 및 젤화 시간(17.28-28.32초)을 나타내었다. 수용성인 젬시타빈을 탑재한 채로 방광 시뮬레이션 모델을 통해 젤 침식 및 약물 방출을 조사하였다. 4회 반복시험 후 남아있는 양을 관찰하였을 때 HHA첨가 하이드로젤 및 PLX 하이드로젤이 각각 74.6% 및 57.8%로 나타났으며, 약물 방출은 확산 및 침식으로 제어되었다. 따라서 HHA 첨가 하이드로젤은 방광 내 주입을 위한 유망한 시스템으로 판단된다
Poloxamer 407 (PLX) hydrogel has been used as a drug delivery system for intravesical instillation, but it has a limitation of insufficient gel strength. Here, to modulate the viscosity and strength of hydrogel, various polymers were screened. Their effect on viscosity decreased in the following order: high molecular-weight hyaluronic acid (HHA; 33.524 Pa·s) > hydroxypropyl methylcellulose > chitosan > low-molecular weight HA > sodium alginate > carbopol (24.332 Pa·s). Polymer addition hardly altered the thermo-reversible property of hydrogels; the gelation temperature was 21.0-25.3 °C and gelation time was 17.28-28.32 s. With gemcitabine as a water-soluble ingredient, gel erosion and drug release were examined using an in vitro bladder simulation model. After four repeated cycles of filling and emptying, the remaining fraction of HHA-added hydrogel and PLX hydrogel was 74.6% and 57.8%, respectively. Furthermore, drug release was diffusion- and erosion-controlled. Thus, HHA-added hydrogel is a promising system for intravesical instillation.
Keywords:poloxamer 407;hydrogel;gemcitabine;hyaluronic acid;intravesical instillation
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