Drug delivery systems for thyroid disease treatment: A mini review on current therapies and alternative approaches

The neuroendocrine and nervous systems play a significant role in regulating and maintaining homeostasis in the human body. The neuroendocrine system facilitates homeostasis by means of secretion and transport of hormones to target sites via the bloodstream, whereas the nervous system allows rapid neuronal communication of information between different regions of the body via the brain, spinal cord and nerves. Both systems are in constant interaction and influence each other with the overall aim of maintaining homeostasis. Neuroendocrine hormones are critical in regulating bodily functions. They have effects on diverse systems such as metabolism, reproduction, electrolyte balance and growth and development [1]. A wide variety of glands distributed throughout the body play a key role in the production and regulation of these hormones (see Fig. 1A).

In humans, the thyroid gland is located in the frontal section of the neck [2] and is responsible for the synthesis, storage and release of thyroid hormones [triiodothyronine (T₃) and thyroxine (T₄)] [3] and iodine [4], with T₃ being the active form of thyroid hormone [5]. In normal circumstances the estimated daily production of T₃ and T₄ is estimated to be 30 μg and 100 μg respectively [6]. Both compounds are active, but thyroid receptors typically have a higher affinity for T₃ (approx. 10-fold higher) versus T₄ [4]. Significantly, studies have shown that daily production of T₃ by the thyroid gland is insufficient to meet daily requirements. Therefore, around 80% of daily T₃ comes from the conversion of T₄ into T₃ via-deiodination catalysed by iodothyronine deiodinases [7,8] (Fig. 1B), the main difference between T₃ and T₄ being the number of iodine groups.

Thyroid hormones are produced by the activation of the thyroid gland by thyroid stimulating hormone (TSH) [9]. In addition to their role in regulation of metabolism and growth development {4, 10} thyroid hormones are also essential in maintaining physical, mental and cardiovascular health [10]. Under normal conditions, thyroid hormone production is controlled by the hypothalamic-pituitary-thyroid (HPT) axis via a negative feedback loop [4]. In this loop, the release of thyrotropin-releasing hormone (TRH) from the hypothalamus is stimulated by low plasma levels of T₄ and T₃. Subsequently, the release of TRH stimulates the release of thyroid-stimulating hormone (TSH) from the pituitary which in turn stimulates the thyroid gland to generate T₃ and T₄. Conversely, high levels of T₃ and T₄ feedback and decrease the production of TRH. A low levels of TRH in turn inhibits the production of TSH, completing the feedback loop [11]. The feedback loop can be seen in Fig. 1C.

The most common types of thyroid disorders are hyperthyroidism and hypothyroidism. The former is characterised by an excess in thyroid hormone production and secretion while the later is characterised by an insufficient thyroid hormone production. The prevalence of these conditions range between 2 and 6% of population [12]. It is important to note that these conditions and their treatment may have significant chronia health implications for patients. This review provides an overview of conventional therapeutic approaches together with new developments in the field of drug delivery with the aim of successfully treating thyroid conditions described in the literature.

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Excipients mentioned in the study beside others: Witepsol H15, Witepsol E 75, PVA, PEG

Laura Kerrigan, Sarah A. Stewart, Juan Domínguez-Robles, Aaron J. Brady, Aiman Abu Ammar, Ryan F. Donnelly, Andi Dian Permana, Eneko Larrañeta, Drug delivery systems for thyroid disease treatment: A mini review on current therapies and alternative approaches, Journal of Drug Delivery Science and Technology, 2023, 104861, ISSN 1773-2247,
https://doi.org/10.1016/j.jddst.2023.104861.