Shihab Uddin
Kyushu University, Japan
Title: Synthesis of widely-soluble biocompatible ionic liquids aiming to enhance transdermal drug delivery system
Biography
Biography: Shihab Uddin
Abstract
Ionic Liquids (ILs) are a novel class of environmentally benign and tailor-made solvents. They have been increasingly exploited as solvents, co-solvents, and/or materials in the fields of pharmaceutical drug delivery and Active Pharmaceutical Ingredient (API) formulation because of their unique properties. ILs ensures potent therapeutic action by solubilizing or stabilizing as well as enhancing skin penetration of drugs in Transdermal Drug Delivery Systems (TDDSs). We’ve developed three novel Lipid-Based Bio-Ils (LBILs), each including a long chain phosphonium cation, the phosphatidylcholine derivative named 1,2-dimyristoyl-sn-glycero-3-ethyl-phosphatidylcholine; EDMPC (similar to natural lipids on the skin) and a long-chain Fatty Acid (FA). In the synthesis of LBILs, EDMPC Chloride (EDMPC-Cl) was first synthesized by a series of reactions under specific conditions. Then, the combination of equimolar amounts of either linoleic, oleic, or stearic acid with the EDMPC-Cl synthesize three LBILs, [EDMPC][Lin], [EDMPC][Ole], and [EDMPC][Ste]. At room temperature, [EDMPC][Lin], [EDMPC][Ole] and [EDMPC][Ste] are viscous liquid, highly viscous liquid and semi-solid respectively. The purity, thermal phase behavior, and identical properties of LBILs were optimized by proton nuclear magnetic resonance (1H NMR), Fourier Transform Infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), Elemental Analysis (EA), Mass Spectroscopy (MS), Dynamic Light Scattering (DLS) and UV visible spectroscopy. The three LBILs were found soluble at an equal ratio in both polar (ethanol, methanol, etc.) and non-polar solvents (hexane, heptane, etc.) solvents. DLS and UV analysis revealed that LBILs were molecularly soluble in nonpolar solvents and dispersible in polar solvents by forming microemulsions/ nanoparticles. Using an artificial three-dimensional human epidermis model these compounds were tested for biocompatibility in a well-established skin irritation test (MTT-assay) only to exhibit excellent biocompatibility. The Ionic-liquid-in-oil-nanodispersions (IL/O-NDs) from three LBILs enhanced the transdermal permeation of the peptide to the skin layers by deforming its lipid and protein arrangements to enhance the transdermal permeation of the peptide compared to other Conventional Skin Permeation Enhancers (CPE) and Tween-80. Transdermal peptide delivery profiles of IL/O-NDs of these three peptide-LBIL complexes revealed that [EDMPC][Lin]/O-ND was the most preferable for a TDDS based on the pharmacokinetic parameters compared to others. These results clearly state the assurance of enhanced TDDS by synthesis of these universal soluble biocompatible Ionic Liquids.