Antimicrobial Imidazolium Ionic Liquids for the Development of Minimal Invasive Calcium Phosphate-Based Bionanocomposites

Abstract

Biofilm formation is one of the main obstacles that occur during in vivo implantation, which compromises the implant functionality and patients' health. This is the inspiration for the development of novel implant materials that contain broad-spectrum antimicrobial activity, including antibacterial and antifungal, and enable the local release of antimicrobial agents. Here, multifunctional calcium phosphate-ionic liquid (IL) materials, possessing antimicrobial and repair/regeneration features plus injectability, are proposed as implants in minimally invasive surgery. This approach was based on the loading of 1-alkyl-3-alkylimidazolium chloride ionic liquids (ILs) (C n MImCl (n = 4, 10, 16) and (C 10 ) 2 MImCl) during the in situ sol−gel synthesis of calcium phosphates (CaP) and study of their effects on CaP crystallization and biological properties. Physical, morphological, and biological investigations were performed to evaluate the bionanocomposites' properties. The IL N-alkyl chain length influenced the crystallization of CaP and, consequently, the biological properties, which afforded bionanocomposites (when loaded with C 16 MImCl or (C 10 ) 2 MImCl) that, (i) inhibit both in vitro bacterial and fungal growth; (ii) reduce the in vitro inflammatory response; (iii) induce osteogenic differentiation in the basal medium of human mesenchymal stem cells; and (iv) are injectable. This will enable the design of multifunctional injectable implants with antimicrobial, anti-inflammatory, and regenerative properties to be used in minimally invasive surgery of bone and maxillofacial defects.

Heterogenized Imidazolium-Based Ionic Liquids in Pebax®Rnew. Thermal, Gas Transport and Antimicrobial Properties

“…Ionic liquids (ILs) are salts displaying a melting point of up to 100 °C and a low vapor pressure combined with a remarkable synthetic flexibility to design their physicochemical properties [ 3 ]. Different studies demonstrated antimicrobial activity of ILs comprising cations based on the imidazole heterocycle (antibacterial, antifungal, antitumor, antioxidant and antifibrous agents) [ 4 , 5 , 6 ]. The insertion of cations into the lipid bilayer cell membranes of microorganisms [ 7 ] causes their structural damage [ 8 ].…”

“…In particular, N-Alkylimidazolium-based ILs are recognized as promising antimicrobial agents [ 9 ], particularly those with long alkyl chains [ 10 , 11 ]. Raucci et al reported that multifunctional calcium phosphate (CaP)-IL materials, based on the loading of 1-alkyl-3-alkylimidazolium chloride ionic liquids (ILs) (CnMImCl ( n = 4, 10, 16) and (C 10 ) 2 MImCl) during the in situ sol−gel synthesis of calcium phosphates (CaP), displayed an antimicrobial activity that increased with an increasing N-alkyl chain length: C 4 MImCl < C 10 MImCl < C 16 MImCl [ 6 ]. N-hexadecyl was identified as an optimum N-alkyl chain length, demonstrating a broad-spectrum toxic effect; this behavior was related to an ideal amphiphilic nature of the 1-n-hexadecyl-3-methylimidazolium cation [ 12 ].…”

Osteogenic and Anti-Inflammatory Behavior of Injectable Calcium Phosphate Loaded with Therapeutic Drugs

“…The calcium phosphate materials (CaPs) were synthesized at room temperature by sol–gel technology as reported in a previous study [ 14 ]. Briefly, CaP were obtained by using calcium nitrate tetrahydrate (Ca(NO 3 ) 2 ·4H 2 O, 99% A.C.S.…”

“…Herein, our objective was to create therapeutic injectable materials to locally treat bone diseases. The CaP-based systems were fabricated through the sol-gel method, which allows obtaining full injectability and nano-hydroxyapatite with low crystallinity mimicking natural bone mineral components [ 14 ]. Furthermore, this technology allows a loading of thermo-sensible drugs in the variously shaped materials and to synthesize organic-inorganic hybrid materials [ 15 , 16 , 17 , 18 ].…”

Imidazolium salts as alternative compounds to control diseases caused by plant pathogenic bacteria

“…They are derivatives of the imidazolium cation and an inorganic or organic anion (Riduan and Zhang ). In medicine and human health, imidazolium salts have been tested for a wide range of applications, such as antifungal (Schrekker et al ), fungal antibiofilm (Raucci et al ), antibacterial (Czekański et al ; Doria et al ), antiparasitic (Martins et al ) and larvicidal (Goellner et al ) agents. With regard to the potential use of imidazolium salts in agriculture, so far, only the results of a single study have been reported.…”