Ahmad Mehdi

Microgels of silylated HPMC as a multimodal system for drug co-encapsulation

Combined therapy is a global strategy developed to prevent drug resistance in cancer and infectious diseases. In this field, there is a need of multifunctional drug delivery systems able to co-encapsulate small drug molecules, peptides, proteins, associated to targeting functions, nanoparticles. Silylated hydrogels are alkoxysilane hybrid polymers that can be engaged in a sol-gel process, providing chemical cross linking in physiological conditions, and functionalized biocompatible hybrid materials. In the present work, microgels were prepared with silylated (hydroxypropyl)methyl cellulose (Si-HPMC) that was chemically cross linked in soft conditions of pH and temperature. They were prepared by an emulsion templating process, water in oil (W/O), as microreactors where the condensation reaction took place. The ability to functionalize the microgels, so-called FMGs, in a one-pot process, was evaluated by grafting a silylated hydrophilic model drug, fluorescein (Si-Fluor), using the same reaction of condensation. Biphasic microgels (BPMGs) were prepared to evaluate their potential to encapsulate lipophilic model drug (Nile red). They were composed of two separate compartments, one oily phase (sesame oil) trapped in the cross linked Si-HPMC hydrophilic phase. The FMGs and BPMGs were characterized by different microscopic techniques (optic, epi-fluorescence, Confocal Laser Scanning Microscopy and scanning electronic microscopy), the mechanical properties were monitored using nano indentation by Atomic Force Microscopy (AFM), and different preliminary tests were performed to evaluate their chemical and physical stability. Finally, it was demonstrated that it is possible to co-encapsulate both hydrophilic and hydrophobic drugs, in silylated microgels, that were physically and chemically stable. They were obtained by chemical cross linking in soft conditions, and without surfactant addition during the emulsification process. The amount of drug loaded was in favor of further biological activity. Mechanical stimulations should be necessary to trigger drug release.

Site-specific grafting on titanium surfaces with hybrid temporin antibacterial peptides

Relying on a membrane-disturbing mechanism of action and not on any intracellular target, antimicrobial peptides (AMP) are attractive compounds to be grafted on the surface of implantable materials such as silicone catheters or titanium surgical implants. AMP sequences often display numerous reactive functions (e.g. amine, carboxylic acid) on their side chains and straightforward conjugation chemistries could lead to uncontrolled covalent grafting, random orientation, and non-homogenous density. To achieve an easy and site specific covalent attachment of unprotected peptides on titanium surfaces, we designed hybrid silylated biomolecules based on the temporin-SHa amphipathic helical antimicrobial sequence. With the grafting reaction being chemoselective, we designed five analogues displaying the silane anchoring function at the N-ter, C-ter or at different positions inside the sequence to get an accurate control of the orientation. Grafting density calculations were performed by XPS and the influence of the orientation of the peptide on the surface was clearly demonstrated by the measure of antimicrobial activity. Temporin amphipathic helices are described to permeabilize the bacterial membrane by interacting in a parallel orientation with it. Our results move in the direction of this mechanism as the selective grafting of hybrid temporin 2 through a lysine placed at the center of the peptide sequence, resulted in better biofilm growth inhibition of E. coli and S. epidermis than substrates in which temporins were grafted via their C- or N-terminus.

Thulium-doped nanoparticles and their properties in silica-based optical fibers

Lasers and amplifiers based on thulium-doped silica fibers require improved spectroscopic properties. In this context, one of the most promising approaches is based on the embedding of thulium ions in nanoparticles of tailored composition and structure. This paper presents various methods used to produce thulium-doped nanoparticles inside silica-based optical fibers. Effects of solution doping method during the elaboration of Modified Chemical Vapor Deposition preform and doping solution composition are studied. A comparison is made between the use of solutions containing LaF3:Tm3+ or YAG:Tm3+ nanoparticles and aluminum-lanthanum-thulium chlorides. Results show that for similar lanthanum content, lanthanum-thulium chlorides doping allows for similar enhancement of 3H4 level of Tm3+ than LaF3:Tm3+ doping. Also, effects of aluminum on 3H4 lifetime enhancement and inhibition of nanoparticle’s formation is discussed.

Molecular dynamics study of rare-earth doped Mg-silicate nanoparticles in vitreous silica: from the preform to the fiber

Formation of rare-earth doped nanoparticles into silica matrix has been modelized by Molecular Dynamics simulations. Preforms with molar composition 0.10MgO–0.90SiO2 and 0.01EuO3/2–0.10MgO–0.89SiO2 have been investigated to have an insight on the structure and chemical composition of the nanoparticles, as well as the rare-earth ions local environment and their clustering. We have finally applied a uniaxal elongation of the rare-earth doped preform in order to mimic the drawing step that changes a preform into a fiber. We present herein first results on the modification of the nanoparticles size distribution.