Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s/n, Madrid 28040, Spain.
Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s/n, Madrid 28040, Spain; Institute of Industrial Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s/n, Madrid 28040, Spain.
Eur J Pharm Sci. 2022 Aug 1;175:106237. doi: 10.1016/j.ejps.2022.106237. Epub 2022 Jun 13.
Neurodegenerative diseases are still a challenge for effective treatments. The high cost of approved drugs, severity of side effects, injection site pain, and restrictions on drug delivery to the Central Nervous System (CNS) can overshadow the management of these diseases. Due to the chronic and progressive evolution of neurodegenerative disorders and since there is still no cure for them, new therapeutic strategies such as the combination of several drugs or the use of existing drugs with new therapeutic applications are valuable strategies. Tetracyclines are traditionally classified as antibiotics. However, in this class of drugs, doxycycline and minocycline exhibit also anti-inflammatory effects by inhibiting microglia/macrophages. Hence, they have been studied as potential agents for the treatment of neurodegenerative diseases. The results of in vitro and in vivo studies confirm the effective role of these two drugs as anti-inflammatory agents in experimentally induced models of neurodegenerative diseases. In clinical studies, satisfactory results have been obtained in Multiple sclerosis (MS) but not yet in other disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), or Amyotrophic lateral sclerosis (ALS). In recent years, researchers have developed and evaluated nanoparticulate drug delivery systems to improve the clinical efficacy of these two tetracyclines for their potential application in neurodegenerative diseases. This study reviews the neuroprotective roles of minocycline and doxycycline in four of the main neurodegenerative disorders: AD, PD, ALS and MS. Moreover, the potential applications of nanoparticulate delivery systems developed for both tetracyclines are also reviewed.
神经退行性疾病仍然是有效治疗的挑战。已批准药物的高成本、副作用的严重程度、注射部位疼痛以及对中枢神经系统 (CNS) 药物输送的限制，可能会影响这些疾病的管理。由于神经退行性疾病具有慢性和进行性演变的特点，而且目前尚无治愈方法，因此，联合使用多种药物或使用具有新治疗应用的现有药物等新的治疗策略具有重要价值。四环素传统上被归类为抗生素。然而，在这类药物中，多西环素和米诺环素通过抑制小胶质细胞/巨噬细胞发挥抗炎作用。因此，它们已被研究作为治疗神经退行性疾病的潜在药物。体外和体内研究的结果证实了这两种药物作为神经退行性疾病实验诱导模型中抗炎剂的有效作用。在临床试验中，在多发性硬化症 (MS) 中取得了令人满意的结果，但在其他疾病如阿尔茨海默病 (AD)、帕金森病 (PD) 或肌萎缩侧索硬化症 (ALS) 中尚未取得结果。近年来，研究人员已经开发和评估了纳米药物递送系统，以提高这两种四环素的临床疗效，为它们在神经退行性疾病中的潜在应用提供了潜力。本研究综述了米诺环素和多西环素在四大主要神经退行性疾病中的神经保护作用：AD、PD、ALS 和 MS。此外，还综述了为这两种四环素开发的纳米递药系统的潜在应用。
