Abstract
Dexamethasone (DEX) is the most commonly prescribed glucocorticoid (GC) and has a wide spectrum of pharmacological activity. However, steroid drugs like DEX can have severe side effects on non-target organs. One strategy to reduce these side effects is to develop targeted systems with the controlled release by conjugation to polymeric carriers. This review describes the methods available for the synthesis of DEX conjugates (carbodiimide chemistry, solid-phase synthesis, reversible addition fragmentation-chain transfer [RAFT] polymerization, click reactions, and 2-iminothiolane chemistry) and perspectives for their medical application as GC drug or gene delivery systems for anti-tumor therapy. Additionally, the review focuses on the development of DEX conjugates with different physical-chemical properties as successful delivery systems in the target organs such as eye, joint, kidney, and others. Finally, polymer conjugates with improved transfection activity in which DEX is used as a vector for gene delivery in the cell nucleus have been described.
Highlights
Glucocorticoids (GC), including dexamethasone (DEX), are the most potent antiinflammatory drugs available, but they can have quite severe acute and chronic systemic side effects [1]
Much research is focused on the development of DEX delivery systems with a release profile that extends from several days to months [13]
This review focuses on the preparation of DEX conjugates with various physicochemical properties and describes
Summary
Glucocorticoids (GC), including dexamethasone (DEX), are the most potent antiinflammatory drugs available, but they can have quite severe acute and chronic systemic side effects [1]. The local administration of DEX in the eye or the joints, as well as inhalation and irrigation applications, can provide the correct dose of the drug directly to the inflamed site and reduce the side effects that can arise with systemic administration. The administration of drugs using extended release delivery systems can control the release and increase the residence time of the drug at the target site, thereby reducing the frequency of doses and the risk of side effects [7,8,9,10,11,12] For this reason, much research is focused on the development of DEX delivery systems with a release profile that extends from several days to months [13]. Descriptions of the methods for their synthesis and the physicochemical characteristics that affect targeted delivery are scarce For these reasons, this review focuses on the preparation of DEX conjugates with various physicochemical properties and describes. Delivery systems hold for providing more appropriate sustained release profiles
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