DES-igning the future of drug delivery: A journey from fundamentals to drug delivery applications

The pharmaceutical industry relies extensively on solvents for various purposes, including synthesis, crystallization, purification, solubilization, and developing drug delivery systems. Deep Eutectic Solvents (DES) represent an advanced class of solvents characterized by their unique attributes, including high polarity, negligible volatility, exceptional thermal resilience, robust ionic conductivity, low melting point, and structural flexibility. Unique physicochemical properties of DES, including density, conductivity, surface tension, and polarity, are intricately connected, and complex behavior in an aqueous environment presents challenges and opportunities across various applications and demands a holistic understanding. In this comprehensive review, we have encapsulated all facets of DES, encompassing diverse preparation methods, detailed exploration of physicochemical properties, solubilization of various Active Pharmaceutical Ingredients (APIs), and elucidation of different delivery routes. DES can be categorized into five primary types based on their compositions and delves into emerging classes like Natural DES (NADES) and Therapeutic DES (THEDES). The introduction of DES derivatives (DESD), Hydrophobic DES (HDES) and Magnetic DES (MDES) further broaden the scope of DES applications. DESs have showcased remarkable potential in drug delivery by enhancing the permeation of active ingredients across and into the skin by acting as promoters of absorption over the skin's outer layers. While we have explored the applications of DES across various routes of administration in this article, the primary focus lies on its potential for topical delivery. Their application in drug delivery through nasal, ocular, and buccal routes holds promise for enhancing therapeutic outcomes. Nevertheless, the toxicity of DESs remains a subject of scrutiny, necessitating systematic evaluation in both in vitro and in vivo studies. Furthermore, this article provides insights into the challenges and offers a glimpse into the future perspectives within the realm of DES. Despite the promising potential of DES in drug delivery, there are currently no approved products based on DES in the market. Their unique properties, coupled with ongoing research and development endeavors, hold the potential to revolutionize drug formulation and delivery.