McMasters James, Poh Scott, Lin Jenny B, Panitch Alyssa
Weldon School of Biomedical Engineering, Purdue University, 206 South Martin Jischke Drive, West Lafayette, IN 47907, United States.
Weldon School of Biomedical Engineering, Purdue University, 206 South Martin Jischke Drive, West Lafayette, IN 47907, United States.
J Control Release. 2017 Jul 28;258:161-170. doi: 10.1016/j.jconrel.2017.05.008. Epub 2017 May 8.
Targeted delivery of anti-inflammatory osteoarthritis treatments have the potential to significantly decrease undesirable systemic side effects and reduce required therapeutic dosage. Here we present a targeted, non-invasive drug delivery system to decrease inflammation in an osteoarthritis model. Hollow thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) nanoparticles have been synthesized via degradation of a N,N'-bis(acryloyl)cystamine (BAC) cross-linked core out of a non-degradable pNIPAM shell. Sulfated 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPSA) was copolymerized in the shell to increase passive loading of an anti-inflammatory mitogen-activated protein kinase-activated protein kinase 2 (MK2)-inhibiting cell-penetrating peptide (KAFAK). The drug-loaded hollow nanoparticles were effective at delivering a therapeutically active dose of KAFAK to bovine cartilage explants, suppressing pro-inflammatory interleukin-6 (IL-6) expression after interleukin-1 beta (IL-1β) stimulation. This thermosensitive hollow nanoparticle system provides an excellent platform for the delivery of peptide therapeutics into highly proteolytic environments such as osteoarthritis.
靶向递送抗炎性骨关节炎治疗药物有可能显著降低不良的全身副作用，并减少所需的治疗剂量。在此，我们展示了一种靶向、非侵入性的药物递送系统，用于减轻骨关节炎模型中的炎症。通过从不可降解的聚N-异丙基丙烯酰胺（pNIPAM）壳层中降解N,N'-双(丙烯酰基)胱胺（BAC）交联核，合成了中空的热响应性聚N-异丙基丙烯酰胺（pNIPAM）纳米颗粒。将硫酸化的2-丙烯酰胺基-2-甲基-1-丙烷磺酸（AMPSA）共聚到壳层中，以增加抗炎性丝裂原活化蛋白激酶激活的蛋白激酶2（MK2）抑制性细胞穿透肽（KAFAK）的被动负载。载药的中空纳米颗粒能够有效地将治疗活性剂量的KAFAK递送至牛软骨外植体，抑制白细胞介素-1β（IL-1β）刺激后的促炎白细胞介素-6（IL-6）表达。这种热敏性中空纳米颗粒系统为将肽治疗药物递送至诸如骨关节炎等高蛋白水解环境提供了一个极佳的平台。
