Biocompatible Ionic Liquid Surfactant-Based Microemulsion as a Potential Carrier for Sparingly Soluble Drugs

Abstract

Developing a universal drug delivery vehicle of sparingly soluble drugs remains a challenge, with surface-active ionic liquid (SAIL)-based ionic liquid-in-oil (IL/O) microemulsions (MEs) being the most suitable vehicles. In this study, a series of SAILs were formulated to prepare novel IL/O MEs composed of SAIL, sorbitan laurate (Span-20), and isopropyl myristate. On the basis of the constructed pseudoternary diagrams, the SAILs played vital surfactant roles with Span-20 acting as a cosurfactant. Excellent drug solubility of MEs prepared with a ratio of 2:1 (SAIL­[Cho]­[Ole]:Span-20) was observed. Examination of the droplet shape, size, and size distribution of the MEs revealed well-distributed particle sizes of 6.5–21.2 nm that formed spherical micelles with the IL 1,3-dimethylimidazolium dimethyl phosphate at the core of the MEs. The MEs showed excellent solubility of sparingly soluble drugs (i.e., celecoxib, acyclovir, methotrexate, and dantrolene sodium). In vitro cytotoxicity of the new carrier using a three-dimensional reconstructed human epidermis model revealed that the cell viability of SAIL-based MEs (94%) was similar when compared to conventional Tween-80-based MEs (96%) at the same IL concentration (4%). The results indicate that the SAIL surfactant in the MEs represents a potential alternative to conventional surfactants for solubilizing insoluble drug molecules.

Upgrading the Topical Delivery of Poorly Soluble Drugs Using Ionic Liquids as a Versatile Tool

“…In this setting, ILs have proven to be a useful approach to increase drug solubility [ 5 , 6 , 23 ] and drug loading [ 24 , 25 , 26 , 27 , 28 ] into drug delivery systems. Nonetheless, these abilities may considerably vary with the type of IL, particularly with their properties and structural composition.…”

pH-Responsive Nanostructures Based on Surface Active Fatty Acid-Protic Ionic Liquids for Imiquimod Delivery in Skin Cancer Topical Therapy

“…Undeniably, in the last few years, the biomedical and pharmaceutical industry has turned increasing attention towards ILs due to their yet unexplored potential as bioactive agents or to their ability to solubilize and stabilize drugs [ 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. Furthermore, the cation and/or anion amphiphilic nature can be finely balanced to trigger the self-assembling behavior of ILs [ 40 , 41 , 42 , 43 , 44 ]. In this framework, fatty acids raised remarkable interest as building blocks for ILs containing natural hydrophobic tails [ 45 , 46 , 47 , 48 , 49 , 50 ] and such materials were investigated in pharmaceutical applications [ 42 , 51 , 52 , 53 , 54 ].…”

“…Furthermore, the cation and/or anion amphiphilic nature can be finely balanced to trigger the self-assembling behavior of ILs [ 40 , 41 , 42 , 43 , 44 ]. In this framework, fatty acids raised remarkable interest as building blocks for ILs containing natural hydrophobic tails [ 45 , 46 , 47 , 48 , 49 , 50 ] and such materials were investigated in pharmaceutical applications [ 42 , 51 , 52 , 53 , 54 ]. An intriguing subclass of ILs is that of the so-called protic ionic liquids (PILs), which are easily prepared by reacting a Brønsted acid and a Brønsted base [ 55 , 56 ].…”

Concentration- and Temperature-Responsive Reversible Transition in Amide-Functionalized Surface-Active Ionic Liquids: Micelles to Vesicles to Organogel

“… 10 − 15 In an attempt to have novel surfactant structures that have ionic liquid (IL) character, the better known as surface-active ionic liquids (SAILs) are studied for their aggregation behavior in an aqueous medium. 16 − 21 Traditional surfactants, although having similar molecular architectures to ILs, do not fit in this category because of their higher melting points (>100 °C). Several groups including our own group have reported the formation of various structural architectures, viz., micelles, wormlike micelles, lamellar, vesicles, coacervates, and gels through (i) self-assembling of these SAILs in aqueous and nonaqueous media, (ii) synergistic interactions of SAILs with various additives, and (iii) stimuli response.…”