Peake Nick J, Pavlov Anton M, D'Souza Alveena, Pingguan-Murphy Belinda, Sukhorukov Gleb B, Hobbs Adrian J, Chowdhury Tina T
Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London , Mile End Road, London E1 4NS, United Kingdom.
Biomacromolecules. 2015 Feb 9;16(2):524-31. doi: 10.1021/bm501575w. Epub 2015 Jan 20.
C-type natriuretic peptide (CNP) exhibits potent anti-inflammatory effects in chondrocytes that have the potential to repair cartilage damage observed in osteoarthritis (OA). However, treatments for OA have been challenging due to poor targeting and delivery of therapeutics. The present study fabricated polyelectrolyte microcapsules loaded with CNP and examined whether the layer-by-layer (LbL) approach could have protective effects in cartilage explants treated with the pro-inflammatory cytokine, interleukin-1β (IL-1β). SEM showed uniform, 2 to 3 μm spherical microcapsules with morphological characteristic similar to templates loaded with or without CNP. The protein was localized around the external surface of the microcapsules with encapsulation efficiencies >82.9%. CNP release profiles were broadly similar following 9 days of culture. The presence of CNP microcapsules did not significantly affect cell viability (80%) with DNA values that remained stable throughout the culture conditions. Confocal imaging showed clustering of microcapsules in chondrocytes to natriuretic peptide receptor (Npr) 2 and 3. Treatment of cartilage explants with CNP microcapsules led to concentration-dependent inhibition of NO release in response to IL-1β and restoration of matrix synthesis. In summary, we demonstrate controlled delivery of CNP to dampen pro-inflammatory effects induced by IL-1β in cartilage explants. The LbL approach has the potential to promote cartilage repair in vivo.
C型利钠肽（CNP）在软骨细胞中表现出强大的抗炎作用，这些软骨细胞具有修复骨关节炎（OA）中观察到的软骨损伤的潜力。然而，由于治疗药物的靶向性和递送性较差，OA的治疗一直具有挑战性。本研究制备了负载CNP的聚电解质微胶囊，并研究了层层（LbL）方法对用促炎细胞因子白细胞介素-1β（IL-1β）处理的软骨外植体是否具有保护作用。扫描电子显微镜显示，负载或未负载CNP的微胶囊呈均匀的2至3μm球形，其形态特征与模板相似。蛋白质定位于微胶囊的外表面，包封率>82.9%。培养9天后，CNP的释放曲线大致相似。CNP微胶囊的存在对细胞活力（80%）没有显著影响，在整个培养条件下DNA值保持稳定。共聚焦成像显示微胶囊在软骨细胞中聚集于利钠肽受体（Npr）2和3。用CNP微胶囊处理软骨外植体导致对IL-1β刺激的NO释放呈浓度依赖性抑制，并恢复基质合成。总之，我们证明了CNP的可控递送可减轻IL-1β在软骨外植体中诱导的促炎作用。层层方法有促进体内软骨修复的潜力。
