Rahman Mahfoozur, Beg Sarwar, Anwar Firoz, Kumar Vikas, Ubale Ruhi, Addo Richard T, Ali Raisuddin, Akhter Sohail
Department of Pharmaceutical Sciences, Shalom Institute of health and allied sciences, SHUATS, Allahabad, India.
University Institute of Pharmaceutical Sciences, Panjab, University, Chandigarh, India.
Crit Rev Ther Drug Carrier Syst. 2017;34(4):283-316. doi: 10.1615/CritRevTherDrugCarrierSyst.2017016067.
Rheumatoid arthritis (RA) is a very painful severe autoimmune disease with complex pathology characterized by progressive chronic inflammation, and devastation of the synovium, cartilage, and other joint-associated structures. Significant advances in research in the area of pathophysiology, diagnosis, drug development, and targeted delivery have led to improved RA therapy and better patient compliance. Targeted drug delivery using liposomal nanomedicines significantly alleviate the challenges with conventional anti-RA medications such as off-target effects, short biological half-life, poor bioavailability, high dose-related toxicity, etc. Liposomal nanomedicines in RA drug targeting offer the opportunity for passive targeting [based on size and polyethylene glycol (PEG)-ylation-mediated enhanced permeability and retention] and active targeting (ligation with antibody or peptides, etc.) and encapsulation of lipophilic, hydrophilic drugs, and/or combinational drugs. However, it has been found recently that such injectable nanomedicines raise the concern of an adverse immune phenomenon called complement activationrelated pseudo allergy (CARPA) and failure of therapy on multiple doses due to accelerated body clearance caused many by anti-PEG immunoglobulin M. To ensure safety and efficacy of RA therapy, these need to be considered along with the common formulation quality parameters. Here, we discuss nanotherapeutic targeting in RA therapy using liposomes. Liposomal nanoparticles are investigated for individual anti-RA drug categories. CARPA issues and pathophysiology with such nanomedicines are also discussed in detail.
类风湿性关节炎(RA)是一种非常疼痛的严重自身免疫性疾病,其病理复杂,特征为进行性慢性炎症以及滑膜、软骨和其他关节相关结构的破坏。在病理生理学、诊断、药物开发和靶向递送领域的研究取得了重大进展,从而改善了类风湿性关节炎的治疗方法并提高了患者的依从性。使用脂质体纳米药物进行靶向给药显著缓解了传统抗类风湿性关节炎药物所面临的挑战,如脱靶效应、生物半衰期短、生物利用度差、高剂量相关毒性等。脂质体纳米药物在类风湿性关节炎药物靶向方面提供了被动靶向(基于尺寸和聚乙二醇(PEG)化介导的增强渗透和滞留)和主动靶向(与抗体或肽等连接)以及包封亲脂性、亲水性药物和/或组合药物的机会。然而,最近发现这种可注射纳米药物引发了一种称为补体激活相关假过敏(CARPA)的不良免疫现象的担忧,并且由于抗PEG免疫球蛋白M导致的体内清除加速,多次给药后治疗失败。为确保类风湿性关节炎治疗的安全性和有效性,需要将这些因素与常见的制剂质量参数一并考虑。在此,我们讨论使用脂质体进行类风湿性关节炎治疗中的纳米治疗靶向。针对各个抗类风湿性关节炎药物类别对脂质体纳米颗粒进行了研究。还详细讨论了此类纳米药物的CARPA问题和病理生理学。