Although levothyroxine is one of the most prescribed medications in the world, its bioavailability has been reported to be impaired by many factors, including interfering drugs or foods and concomitant diseases, and persistent hypothyroidism with a high dose of levothyroxine is thus elicited. Persistent hypothyroidism can also be induced by noninterchangeability between formulations and poor compliance. To address these issues some strategies have been developed. Novel formulations (liquid solutions and soft gel capsules) have been designed to eliminate malabsorption. Some other delivery routes (injections, suppositories, sprays, and sublingual and transdermal administrations) are aimed at circumventing different difficulties in dosing, such as thyroid emergencies and dysphagia. Moreover, nanomaterials have been used to develop delivery systems for the sustained release of levothyroxine to improve patient compliance and reduce costs. Some delivery systems encapsulating nanoparticles show promising release profiles. In this review, we first summarize the medical conditions that interfere with the bioavailability of oral levothyroxine and discuss the underlying mechanisms and treatments. The efficacy of liquid solutions and soft gel capsules are systematically evaluated. We further summarize the novel delivery routes for levothyroxine and their possible applications. Nanomaterials in the levothyroxine field are then discussed and compared based on their load and release profile. We hope the article provides novel insights into the drug delivery of levothyroxine.

中文翻译：

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左旋甲状腺素：传统和新型药物输送制剂。

虽然左旋甲状腺素是世界上处方最多的药物之一，但据报道其生物利用度会受到许多因素的影响，包括干扰药物或食物以及伴随疾病，因此会引起持续性甲状腺功能减退症和高剂量的左旋甲状腺素。持续性甲状腺功能减退症也可能由制剂之间的不可互换性和依从性差引起。为了解决这些问题，已经制定了一些策略。新的配方（液体溶液和软胶囊）被设计用来消除吸收不良。其他一些给药途径（注射剂、栓剂、喷雾剂以及舌下和经皮给药）旨在规避不同的给药困难，例如甲状腺急症和吞咽困难。而且，纳米材料已被用于开发持续释放左旋甲状腺素的递送系统，以提高患者的依从性并降低成本。一些封装纳米颗粒的递送系统显示出有前途的释放曲线。在这篇综述中，我们首先总结了影响口服左旋甲状腺素生物利用度的医疗条件，并讨论了潜在的机制和治疗方法。系统地评估了液体溶液和软胶囊的功效。我们进一步总结了左旋甲状腺素的新递送途径及其可能的应用。然后根据它们的负载和释放曲线讨论和比较左旋甲状腺素领域中的纳米材料。我们希望这篇文章能为左旋甲状腺素的药物输送提供新的见解。