Drug delivery systems based on pharmaceutically active ionic liquids and biocompatible poly(lactic acid)
2014
Jouannin, Claire | Tourné-Péteilh, Corine | Darcos, Vincent | Sharkawi, Tahmer | Devoisselle, Jean-Marie | Gaveau, Philippe | Dieudonné, Philippe | Vioux, André | Viau, Lydie
Poly(l-lactic acid) (PLLA) membranes containing pharmaceutically active ionic liquids (API–ILs) have been prepared by using a simple film casting from solvent evaporation method. Several sets of membranes were prepared from two different ionic liquids namely 1-methyl-3-butyl-imidazolium ibuprofenate (C₄MImIbu) and lidocainium ibuprofenate (LidIbu) with different API–IL contents. Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Wide-Angle and Small-Angle X-ray Scattering (WAXS and SAXS) revealed the strong influence of both the IL nature and content on the morphology and the crystallinity of the resulting PLLA. At 20 weight%, LidIbu was shown to act as a plasticizer for PLLA and homogeneous membranes were obtained. In contrast, at the same IL content, phase separation occurred using C₄MImIbu, resulting in the formation of porous PLLA. An increase of LidIbu content to 50 weight% results also in phase separation. ¹H and ¹H–¹³C CP-MAS NMR measurements evidenced the influence of different morphologies and crystallinities on IL mobility. C₄MImIbu was found to be highly mobile whereas the mobility of LidIbu was content dependent. At low percent, low mobility was observed while at higher content, two populations with respectively high and low mobility were observed. These PLLA–IL membranes were further tested as drug delivery systems. In accordance with the morphology and mobility obtained, we demonstrated that release kinetics from PLLA membranes can be tuned by the nature and the content of API–ILs. Sustainable release kinetics were obtained with API–IL acting as a plasticizer while the fastest release was obtained with API–IL acting as a porogenic agent.
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