Drug delivery systems for thyroid disease treatment: A mini review on current therapies and alternative approaches
Thyroid hormones play an important role in many metabolic processes in the human body. However, these processes can often be disrupted by an over or underactivity of the thyroid gland which, if undiagnosed or untreated, can result in serious illness. Currently, therapeutic management of an underactive thyroid gland (hypothyroidism) is typically achieved via replacement therapy with levothyroxine (LEVO), a synthetic form of thyroxine. Conversely, anti-thyroid drugs (ATDs), radioactive iodine or thyroidectomy are established approaches in treating hyperthyroidism. With respect to the route of the administration, drugs to treat hypo and hyperthyroidism can typically be administered through oral (PO), intravenous (IV), and rectal (PR) routes. Despite the fact that thyroid disorders have been successfully treated for many years, several problems still exist in the conventional treatment approach. Due to issues such as poor patient compliance and concordance, poor gastrointestinal (GI) absorption when taken incorrectly, and interactions with food and other medications, the administration of these drugs often results in sub-optimal dosing with accompanying serious illness if not corrected. Other forms of drug delivery are currently being studied to overcome the dosing complications that frequently occur with LEVO and ATDs with a view to increasing both patient compliance and bioavailability of the drugs in question. This review will examine why there remains a need for novel approaches and discuss studies that have been carried out with regards to this.
1. Introduction
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.