Jiang Tao, Kan Ho-Man, Rajpura Komal, Carbone Erica J, Li Yingcui, Lo Kevin W-H
Institute for Regenerative Engineering, University of Connecticut Health Center, School of Medicine, Farmington, CT 06030, USA.
Department of Biology, College of Arts and Sciences, University of Hartford, West Hartford, CT 06117, USA.
J Nanosci Nanotechnol. 2018 Apr 1;18(4):2310-2317. doi: 10.1166/jnn.2018.14311.
Osteoarthritis is a severe and debilitating joint disease, which is characterized as results from damage and degeneration of the articular cartilage of the joint surfaces. The incidence of osteoarthritis is growing increasingly high while current treatment methods remain suboptimal. The major issue for current osteoarthritic medications is that patients frequently experience adverse, nonspecific side effects that are not a direct result of the specific pharmacological action of the drug. The treatment processes could be made more effective, safe, and comfortable if it were possible to deliver the drugs specifically to cartilage tissue. Therefore, developing site-specific and controlled drug release delivery systems is needed for overcoming the aforementioned issues. We have developed a poly(lactic-co-glycolic acid) (PLGA)-based nanoscale drug delivery system based on a short cartilage-targeting peptide sequence: WYRGRL. Nanoparticles (NPs) made of methoxy-poly(ethylene glycol) (PEG)-PLGA and maleimide-PEG-PLGA were prepared using a water-in-oil-in-water double emulsion and solvent evaporation method. Fluorescein isothiocyanate (FITC)-tagged WYRGRL peptide was then linked to the surface of the nanoparticles through the alkylation reaction between the sulfhydryl groups at the N-terminal of the peptide and the C═C double bond of maleimide at one end of the polymer chain to form thioether bonds. The conjugation of FITC-tagged WYRGRL peptide to PLGA NPs was confirmed by NMR technique. We further demonstrated that the novel delivery system binds very specifically to cartilage tissue in vitro and ex vivo. Given that biodegradable PLGA-based NPs have shown promise for drug delivery, they could be used for a positive advancement for treatments of osteoarthritic patients by creating a more effective treatment process that achieves healing results faster and with fewer deleterious side effects. Taken together, these promising results indicated that this nanoscale targeting drug delivery system was able to bind to cartilage tissue and might have a great potential for treating osteoarthritis.
骨关节炎是一种严重且使人衰弱的关节疾病，其特征是关节表面的关节软骨受损和退化。骨关节炎的发病率日益升高，而目前的治疗方法仍不尽人意。当前骨关节炎药物的主要问题是患者经常会经历不良的、非特异性的副作用，这些副作用并非药物特定药理作用的直接结果。如果能够将药物特异性地递送至软骨组织，治疗过程可能会更有效、安全且舒适。因此，需要开发位点特异性和可控药物释放递送系统来克服上述问题。我们基于一种短的软骨靶向肽序列：WYRGRL，开发了一种聚乳酸-羟基乙酸共聚物（PLGA）基纳米级药物递送系统。采用水包油包水双乳液和溶剂蒸发法制备了由甲氧基聚乙二醇（PEG）-PLGA和马来酰亚胺-PEG-PLGA制成的纳米颗粒（NPs）。然后，通过肽N端的巯基与聚合物链一端马来酰亚胺的C═C双键之间的烷基化反应，将异硫氰酸荧光素（FITC）标记的WYRGRL肽连接到纳米颗粒表面，形成硫醚键。通过核磁共振技术证实了FITC标记的WYRGRL肽与PLGA NPs的缀合。我们进一步证明，这种新型递送系统在体外和离体实验中都能非常特异性地与软骨组织结合。鉴于基于可生物降解PLGA的NPs在药物递送方面已显示出前景，它们可用于通过创建更有效的治疗过程来积极推进骨关节炎患者的治疗，该过程能更快地实现治愈效果且副作用更少。综上所述，这些有前景的结果表明，这种纳米级靶向药物递送系统能够与软骨组织结合，并且在治疗骨关节炎方面可能具有巨大潜力。
