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아주대학교

J. Control. Release, Jun 26 2024, 372 S0168-3659(24)00383-3 | https://doi.org/10.1016/j.jconrel.2024.06.034 Intra-articular hydrogel formulation prolongs the in vivo stability of Toll-like receptor antagonistic peptides for rheumatoid arthritis treatment

Soyeon Lee ^a, Sangdun Choi ^a, Moon Suk Kim^a,b

^aDepartment of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea

^bResearch Institute, Medipolymers, Woncheon Dong 332-2, Suwon 16522, Republic of Korea

Corresponding author : Moon Suk Kim

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation that primarily affects joint tissue and requires frequent medication. Recently, we developed cyclic phage-display-derived inhibitory peptides (CPs), which act as Toll-like Receptor 4 antagonists. These CPs exhibited therapeutic efficacy against joint diseases by alleviating inflammatory factors. Nonetheless, CP exhibits in vivo instability and a short half-life. Therefore, this study sought to improve the in vivo stability of CP, thereby reducing the frequency of CP administration through the development of an injectable hydrogel depot formulation. To improve in vivo stability, CP was chemically conjugated to hyaluronic acid (HA-CP) and subsequently mixed into a temperature-sensitive hydrogel [methoxy polyethylene glycol-b-poly(ε-caprolactone)-ran-poly(lactide) (PC)] as an injectable depot (PC+(HA-CP)). For comparison, CP was physically mixed with HA and PC (PC+(HA+CP)). Both PC+(HA-CP) and PC+(HA+CP) were found to rapidly form depots upon injection into the joint space. Cell viability assays confirmed the non-toxic nature of PC+(HA-CP) and PC+(HA+CP), whereas both formulations exhibited inhibition of inflammatory factors. Furthermore, PC+(HA-CP) retained CP for a longer duration compared to PC+(HA+CP) in the presence of hyaluronidase and within the RA joint space. Following intra-articular injection, both the PC+(HA-CP) and PC+(HA+CP) depots exhibited reductions in RA symptoms, cartilage regeneration, and suppression of pro-inflammatory cytokine levels. Specifically, by extending the in vivo retention of CP, PC+(HA-CP) demonstrated superior RA treatment efficacy compared to PC+(HA+CP). In conclusion, intra-articular injection of PC+(HA-CP) was validated as an effective strategy for treating RA, owing to its ability to prolong the in vivo retention of CP. This approach holds promise for improving RA management and patient outcomes.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-07-09)
연구진국내 연구진
분야 바이오·의료융합 > 바이오소재

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