Tran Thanh-Huyen, Amiji Mansoor M
Northeastern University, Bouve College of Health Sciences, School of Pharmacy, Department of Pharmaceutical Sciences , Boston, MA 02115 , USA +1 617 373 3137 ; +1 617 373 8886 ;
Expert Opin Drug Deliv. 2015 Mar;12(3):393-414. doi: 10.1517/17425247.2015.972931. Epub 2014 Nov 4.
Inflammatory diseases, including autoimmune diseases and autoinflammatory diseases, are characterized by the imbalance of pro-inflammatory cytokines and anti-inflammatory cytokines. Targeted systems allow for specific delivery and sustained release of biological agents to inflamed tissues and macrophages, hence reducing their side effects.
This review discusses various targeting strategies for biological therapies of inflammatory diseases, with a focus on modulating macrophage functional polarization from an M1 to M2 phenotype. Furthermore, recent advances in the development of targeted delivery systems for gene therapy against inflammatory diseases including liposomal therapeutics, polymeric nanoparticles and microspheres, and multi-compartmental delivery systems are summarized.
Molecular advances have uncovered various targets for biological therapies against inflammatory diseases. Despite substantial promise, the potential translation from the bench to the clinic is limited due to poor systemic stability of the delivery systems, low tissue distribution, and safety concerns. In order to develop clinically translatable targeted delivery systems, thorough evaluation of the efficacy and toxicity in relevant animal models and in different inflammatory diseases is needed. In addition, issues related to long-term storage stability, scale-up and manufacturing of the systems need to be addressed.
炎症性疾病,包括自身免疫性疾病和自身炎症性疾病,其特征在于促炎细胞因子和抗炎细胞因子的失衡。靶向系统能够将生物制剂特异性递送至炎症组织和巨噬细胞并实现持续释放,从而减少其副作用。
本综述讨论了炎症性疾病生物治疗的各种靶向策略,重点是调节巨噬细胞从M1表型向M2表型的功能极化。此外,还总结了用于炎症性疾病基因治疗的靶向递送系统的最新进展,包括脂质体疗法、聚合物纳米颗粒和微球以及多室递送系统。
分子研究进展揭示了炎症性疾病生物治疗的各种靶点。尽管前景广阔,但由于递送系统的全身稳定性差、组织分布低以及安全性问题,从实验室到临床的潜在转化受到限制。为了开发可临床转化的靶向递送系统,需要在相关动物模型和不同炎症性疾病中对疗效和毒性进行全面评估。此外,还需要解决与系统的长期储存稳定性、放大生产和制造相关的问题。