Foam-Based Bionanocomposite Scaffold for Bone Tissue Engineering

The repair of large bone defects is a major clinical problem for which tissue engineering (association of a biomaterial and cells) constitutes a valuable alternative. In this domain, the architecture and the mechanical properties of the 3D scaffold aimed to support cells is of key importance to succeed in bone reconstruction. In this study, we aim to design and evaluate a bionanocomposite foam-based scaffold, exhibiting all the desired biofunctional attributes of biocompatibility, bioactivity, osteoconduction/induction, combined with potential release properties. To perform this, 2 components have been associated: (i) a biopolymer, pectin, incorporating (ii) calcium phosphate nanoparticules to provide bone apatite nucleation sites, mechanical reinforcement, and to play the role of potential drug reservoir. The goal of this study was to determine the feasibility of obtention of such bionanocomposite by foam-templating, and to study the influence of mineral particules ratio on pectin foam and final scaffold 3D architecture and properties

Solid-state NMR characterization of drug-model molecules encapsulated in MCM-41 silica

International audienceIn this contribution, we present a solid-state NMR approach to characterize drugmodel molecules as ibuprofen, benzoic acid, and lauric acid, encapsulated in MCM-41 silica and submitted to strong confinement effects. In particular, we show that by a careful choice of the solid-state NMR sequences, it is possible to efficiently characterize these highly mobile molecules and their interactions with the pore surface. Thus, we demonstrate that 13C NMR spectroscopy is a powerful tool to characterize and even quantify entrapped and non-entrapped species by using either single-pulse excitation (SPE) or cross-polarization (CP). Whereas the standard {1H}-13C CP experiment is of poor efficiency for mobile species, we show that 13C signal-to-noise (S/N) ratio can be significantly improved through 1H-13C cross-relaxation (namely, nuclear Overhauser effect, nOe) by using a 1H power-gated technique. The long transversal relaxation times [T2(1H) up to 22 ms] observed allow the setup of J-coupling-based experiments such as 2D {1H}-13C heteronuclear multiple-quantum coherence (HMQC) in order to fully characterize the encapsulated molecules. Thus, we demonstrate that the use of sequences derived from solution-state NMR such as these two latter experiments is highly efficient to characterize highly mobile organic molecules trapped in mesopores. Finally, we show that 1H spin diffusion-based experiments can give useful information on the proximities between trapped molecules and the silica surfac

Formulation of ascorbic acid microemulsions with alkyl polyglycosides

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Surfactant Behavior of Ionic Liquids Involving a Drug: From Molecular Interactions to Self-Assembly

International audienceAggregates formed in an aqueous medium by three ionic liquids CnMImIbu made up of 1-alkyl-3-methyl-imidazolium cation (n = 4, 6, 8) and ibuprofenate anion are investigated. Dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), 1H nuclear magnetic resonance measurements, and atom-scale molecular dynamics simulations are used to shed light on the main interactions governing the formation of the aggregates and their composition. At high concentration, mixed micelles are formed with a composition that depends on the imidazolium alkyl chain length. For the shortest alkyl chain, micelles are mainly composed of ibuprofenate anions with some imidazolium cations intercalated between the anions. Upon increasing the alkyl chain length, the composition of the aggregates gets enriched in imidazolium cations and aggregates of stoichiometric composition are obtained. Attractive interactions between these aggregates led to the formation of larger aggregates. As suggested by molecular simulations, these larger aggregates might constitute the early stage of phase separation. Transitions from micelles to vesicles or ribbons are observed due to dilution effects and changes in the chemical composition of the aggregates. We also show that aggregation can be probed using simple microscopic quantities such as radial distribution functions and average solvation numbers

Drug nano-domains in spray-dried ibuprofen-silica microspheres

International audienceSilica microspheres encapsulating ibuprofen in separated domains at the nanometre scale are formed by spray-drying and sol-gel processes. A detailed 1H and 13C NMR study of these microspheres shows that ibuprofen molecules are mobile and are interacting through hydrogen bonds with other ibuprofen molecules. 1H magnetisation exchange NMR experiments were employed to characterize the size of the ibuprofen domains at the nanometre scale. These domains are solely formed by ibuprofen, and their diameters are estimated to be B40 nm in agreement with TEM observations. The nature and formation of these particular texture and drug dispersion are discussed

Sol–gel one-pot synthesis in soft conditions of mesoporous silica materials ready for drug delivery system

The present work reveals a new and simple strategy, a one-step sol–gel procedure, to encapsulate a low water-soluble drug in silica mesostructured microparticles and to improve its release in physiological media. The synthesis of these new materials is based on the efficient solubilisation of a poorly water-soluble drug in surfactant micelles (Tween 80, a pharmaceutical excipient) which act as template for the silica network. A strict control of the sol–gel process and the parameters procedure in soft conditions (concentration, pH, temperature) was applied to reach the solubilisation limit of the drug in the micellar solution so as to optimise its encapsulation. Even if this one-pot procedure could appear limited by the low drug loading, it could provide an interesting alternative for the formulation of many recent highly active but very poorly soluble drugs.Nanostructured MaterialsApplied Science

Drug delivery systems based on pharmaceutically active ionic liquids and biocompatible poly(lactic acid)

International audiencePoly(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

Probing the mobility of ibuprofen confined in MCM-41 materials using MAS-PFG NMR and hyperpolarised-Xe-129 NMR spectroscopy

International audienceThe continuous-flow hyperpolarised (HP)-Xe-129 NMR and magic angle spinning-pulsed field gradient (MAS-PFG) NMR techniques have been used for the first time to study the distribution and the dynamics of ibuprofen encapsulated in MCM-41 with two different pore diameters