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

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.

keywords

BACTERIAL CELLULOSE MEMBRANES; TRANSDERMAL DELIVERY; BIOCELLULOSE MEMBRANES; CONTROLLED-RELEASE; DISSOLUTION; SYSTEMS; COMPOSITES; NAPROXEN; NSAIDS

subject category

Chemistry; Science & Technology - Other Topics; Engineering

authors

Chantereau, G; Sharma, M; Abednejad, A; Neves, BM; Sebe, G; Coma, V; Freire, MG; Freire, CSR; Silvestre, AJD

Groups

G4 - Renewable Materials and Circular Economy
G5 - Biomimetic, Biological and Living Materials

Projects

EJD-FUNMAT - European Joint Doctorate in Functional Materials Research (EJD-FUNMAT)

CICECO - Aveiro Institute of Materials (UID/CTM/50011/2019)

acknowledgements

This work was developed within the scope of the European Joint Doctorate in Functional Materials Research EJD FunMat (Grant agreement ID: 641640) which funded G.C.'s Ph.D. fellowship. LCPO, CNRS UMR 5629, CICECO-Aveiro Institute of Materials FCT Ref. UID/CTM/50011/2019, and iBiMED (UID/BIM/04501/2013 and UID/BIM/04501/2019), financed by national funds through the FCT/MEC and when appropriate cofinanced by FEDER under the PT2020 Partnership Agreement, are also acknowledged. C.S.R.F. acknowledges FCT for her research contract under Stimulus of Scientific Employment 2017 (CEECIND/00464/2017). This article was presented at the 13th International Chemical and Biological Engineering Conference (CHEM-POR 2018). The authors acknowledge the Scientific and Organizing Committees of the Conference for the opportunity to present this work.