Design of Nonsteroidal Anti-Inflammatory Drug-Based Ionic Liquids with Improved Water Solubility and Drug Delivery

authors	Chantereau, G; Sharma, M; Abednejad, A; Neves, BM; Sebe, G; Coma, V; Freire, MG; Freire, CSR; Silvestre, AJD
nationality	International
journal	ACS SUSTAINABLE CHEMISTRY & ENGINEERING
author keywords	Nonsteroidal anti-inflammatory drugs; Ionic liquids; Cholinium cation; Bacterial nanocellulose; Topical drug delivery
keywords	BACTERIAL CELLULOSE MEMBRANES; TRANSDERMAL DELIVERY; BIOCELLULOSE MEMBRANES; CONTROLLED-RELEASE; DISSOLUTION; SYSTEMS; COMPOSITES; NAPROXEN; NSAIDS
abstract	We here report the synthesis of ionic liquids (ILs) composed of the cholinium cation and anions derived from nonsteroidal anti-inflammatory drugs (NSAIDs), namely ibuprofen, ketoprofen, and (S)-naproxen, and their incorporation into bacterial nanocellulose envisaging their use in topical drug delivery systems. The chemical structure of the synthesized ILs was confirmed by spectroscopic techniques, and thermal analysis confirming their categorization as ionic liquids with melting temperatures below 100 degrees C and resistance to autoclaving. The synthesized ILs display an aqueous solubility (at pH 7.4) ranging between 120 and 360 mM, which is up to 100 times higher than the solubility of the respective NSAID precursors, thus contributing to improved bioavailability. Their incorporation into bacterial cellulose originated transparent and homogeneous membranes. Thermogravimetric analysis (stable up to at least 225 degrees C) and mechanical assays (with minimum Young's modulus of 937 MPa, maximum stress of 33 MPa and elongation at break of 5.6%) confirmed the suitability of the prepared membranes for application as topical drug delivery systems. Furthermore, the rehydration ability of IL-incorporated membranes is 18 to 26 times higher than bacterial cellulose, being valuable to the absorption of exudates. Release tests demonstrated a faster and complete release of the IL-based drugs when compared with the starting NSAIDs. Finally, it is demonstrated that bacterial cellulose is not cytotoxic nor proinflammatory, whereas the cytotoxicity and anti-inflammatory properties of IL-incorporated BC membranes are similar to those of NSAIDs or ILs, reinforcing their suitability as envisioned materials for topical drug release applications.
publisher	AMER CHEMICAL SOC
issn	2168-0485
year published	2019
volume	7
issue	16
beginning page	14126
ending page	14134
digital object identifier (doi)	10.1021/acssuschemeng.9b02797
web of science category	Chemistry, Multidisciplinary; Green & Sustainable Science & Technology; Engineering, Chemical
subject category	Chemistry; Science & Technology - Other Topics; Engineering
unique article identifier	WOS:000482173100052