단백질약물의 경구 투여시 발생하는 위장관 내 변성 및 낮은 소장 흡수율 문제를 극복하기 위해, pH 감응성과 점 막점착성을 동시에 지닌 P(AA-co-GelMA) 수화젤 입자를 합성하였다. 천연 젤라틴을 중합반응에 참여시키기 위하여 메타크릴레이트 그룹을 도입한 메타크릴레이트 젤라틴 (GelMA)를 제조하고, 이를 아크릴산 (AA)와 현탁중합시켜 구형의 수화젤 입자를 합성하였다. 합성된 수화젤 입자는 위장 모사 환경 (pH 2.0)에서는 수축된 상태를, 소장 모사 환경(pH 7.0)에서는 급격히 팽윤하는 pH 감응성을 나타내었다. 경사흐름 시스템을 이용한 점막점착성 평가 결과, P(AA- co-GelMA) 수화젤 내 젤라틴의 함량이 증가할수록 점막점착성이 증가하였으며, 실제 장관 환경보다 가혹한 전단응력 조건에서도 점막점착성을 보여주어, 실제 생체 내 환경에서는 더욱 뛰어난 체류 성능을 발휘할 것으로 기대할 수 있었다. 결론적으로 본 연구의 P(AA-co-GelMA) 수화젤 입자는 위장관 환경에 적응하여 단백질약물을 선택적으로 방출하고, 소장내 체류시간을 연장시킴으로써 생체 이용률을 극대화할 수 있는 유용한 경구용 단백질 약물전달 기술로 활용될 수 있을 것이다.

To overcome the challenges of gastrointestinal degradation and low intestinal absorption associated with the oral administration of protein drugs, pH-responsive and mucoadhesive P(AA-co-GelMA) hydrogel particles were  synthesized.  The  methacrylate  groups  were  introduced  into  native  gelatin  to  make  methacrylated  gelatin (GelMA)  capable  of  copolymerizing  with  acrylic  acid  (AA)  via  suspension  polymerization  to  form  spherical particles. The synthesized hydrogel particles exhibited distinct pH-sensitivity, maintaining a collapsed state in a simulated  gastric  environment  (pH  2.0)  and  rapidly  swelling  in  a  simulated  intestinal  environment  (pH  7.0). Mucoadhesion evaluations using a slope flow system demonstrated that the mucoadhesion of the hydrogel increased with  higher  gelatin  content  within  the  P(AA-co-GelMA)  hydrogels.  Additionally,  the  hydrogels  retained  their mucoadhesion even under harsh shear stress conditions far more severe than those of the actual intestinal tract, indicating that they are highly expected to exhibit superior retention performance in actual in vivo environments. In conclusion, the P(AA-co-GelMA) hydrogel particles developed in this study can serve as a promising platform technology for oral protein drug delivery, maximizing bioavailability by selective drug release and prolonging the residence time in the small intestine.

pH-responsive, Mucoadhesive, Hydrogels, Oral protein delivery

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