Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21702, USA.
Molecules. 2020 Dec 31;26(1):175. doi: 10.3390/molecules26010175.
The chloroquine family of antimalarials has a long history of use, spanning many decades. Despite this extensive clinical experience, novel applications, including use in autoimmune disorders, infectious disease, and cancer, have only recently been identified. While short term use of chloroquine or hydroxychloroquine is safe at traditional therapeutic doses in patients without predisposing conditions, administration of higher doses and for longer durations are associated with toxicity, including retinotoxicity. Additional liabilities of these medications include pharmacokinetic profiles that require extended dosing to achieve therapeutic tissue concentrations. To improve chloroquine therapy, researchers have turned toward nanomedicine reformulation of chloroquine and hydroxychloroquine to increase exposure of target tissues relative to off-target tissues, thereby improving the therapeutic index. This review highlights these reformulation efforts to date, identifying issues in experimental designs leading to ambiguity regarding the nanoformulation improvements and lack of thorough pharmacokinetics and safety evaluation. Gaps in our current understanding of these formulations, as well as recommendations for future formulation efforts, are presented.
氯喹类抗疟药物的应用历史悠久，可追溯至几十年前。尽管临床应用经验丰富，但该类药物最近才被发现具有新的用途，包括用于自身免疫性疾病、传染病和癌症。短期使用氯喹或羟氯喹，在无诱发疾病的患者中，传统治疗剂量是安全的，但大剂量和长期使用会导致毒性，包括视网膜毒性。这些药物的其他缺点还包括药代动力学特征，需要延长给药时间以达到治疗组织浓度。为了改善氯喹治疗，研究人员转向氯喹和羟氯喹的纳米医学制剂改造，以增加靶组织相对于非靶组织的暴露量，从而提高治疗指数。这篇综述重点介绍了迄今为止的这些制剂改造工作，确定了实验设计中存在的问题，这些问题导致对纳米制剂改进的模糊认识，以及缺乏彻底的药代动力学和安全性评估。提出了我们目前对这些制剂的理解存在的差距，以及对未来制剂工作的建议。
