Polymeric Microneedles for Transdermal Delivery of Human Placental Tissue for the Treatment of Osteoarthritis.

IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jithu Jerin James, Suman Pahal, Anbu Jayaraman, Damodar Nayak A, Sridhar Koteshwar Narasimhachar, Sudarson Sundarrajan, Basavaraj Basappa Veerabhadraiah, Bharath Srinivasan, Praveen K Vemula, Thanh D Nguyen, Sandhya Kadamboor Veethil
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Abstract

Biologics targeting matrix-degrading proteases, cartilage repair, and inflammation are emerging as promising approaches for osteoarthritis (OA) treatment. Recent research highlights biologic-human placental tissue (HPT) as a potential OA therapy due to its biocompatibility, abundant protein biofactors, and ability to reduce cartilage degradation by suppressing protease expression. Microneedles (MNs) are receiving growing attention for enhancing transdermal delivery of biologics as an alternative to conventional subcutaneous injections. The lyophilized human placental extract (LHP) loaded polymeric MNs are fabricated using a micromolding technique for transdermal delivery. Ex vivo release studies reveal that MNs exhibit a gradual and consistent release of LHP, indicating a sustained delivery profile. LHP-MNs are nontoxic and anti-inflammatory in nature against human skin cells and interleukin (IL-1β) induced synovial cells. Furthermore, the in vivo study shows that LHP-MNs substantially improve behavioral parameters in OA rat models and lower serum concentrations of tumor necrosis factor- α (TNF-α) and cartilage oligomeric matrix protein (COMP) biomarkers, thereby alleviating knee and ankle joint injuries. Histopathological analysis indicates that LHP-MNs significantly preserve cartilage integrity. The study results suggest that employing polymeric MNs for transdermal delivery of LHP can be a promising treatment approach for OA, with the added benefit of excellent patient compliance.

经皮给药人胎盘组织的聚合微针治疗骨关节炎。
靶向基质降解蛋白酶、软骨修复和炎症的生物制剂正在成为治疗骨关节炎(OA)的有希望的方法。最近的研究强调了生物-人胎盘组织(HPT)作为一种潜在的OA治疗方法,因为它具有生物相容性,丰富的蛋白质生物因子,以及通过抑制蛋白酶表达来减少软骨降解的能力。微针(MNs)作为传统皮下注射的替代方案,因其增强生物制剂的透皮给药而受到越来越多的关注。冻干人胎盘提取物(LHP)负载的聚合物纳米颗粒是利用微成型技术制备的透皮给药。体外释放研究表明,MNs表现出逐渐和一致的LHP释放,表明持续给药。LHP-MNs对人类皮肤细胞和白细胞介素(IL-1β)诱导的滑膜细胞无毒和抗炎。此外,体内研究表明,LHP-MNs显著改善OA大鼠模型的行为参数,降低血清中肿瘤坏死因子-α (TNF-α)和软骨寡聚基质蛋白(COMP)生物标志物的浓度,从而减轻膝关节和踝关节损伤。组织病理学分析表明,LHP-MNs可显著保护软骨的完整性。研究结果表明,采用聚合物MNs经皮给药LHP是治疗OA的一种很有前景的方法,而且患者的依从性也很好。
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来源期刊
Macromolecular bioscience
Macromolecular bioscience 生物-材料科学:生物材料
CiteScore
7.90
自引率
2.20%
发文量
211
审稿时长
1.5 months
期刊介绍: Macromolecular Bioscience is a leading journal at the intersection of polymer and materials sciences with life science and medicine. With an Impact Factor of 2.895 (2018 Journal Impact Factor, Journal Citation Reports (Clarivate Analytics, 2019)), it is currently ranked among the top biomaterials and polymer journals. Macromolecular Bioscience offers an attractive mixture of high-quality Reviews, Feature Articles, Communications, and Full Papers. With average reviewing times below 30 days, publication times of 2.5 months and listing in all major indices, including Medline, Macromolecular Bioscience is the journal of choice for your best contributions at the intersection of polymer and life sciences.
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