Thiol-ene Reaction: An Efficient Tool to Design Lipophilic Polyphosphoesters for Drug Delivery Systems.

Poly(ethylene glycol)-b-polyphosphoester (PEG-b-PPE) block copolymer nanoparticles are promising carriers for poorly water soluble drugs. To enhance the drug loading capacity and efficiency of such micelles, a strategy was investigated for increasing the lipophilicity of the PPE block of these PEG-b-PPE amphiphilic copolymers. A PEG-b-PPE copolymer bearing pendant vinyl groups along the PPE block was synthesized and then modified by thiol-ene click reaction with thiols bearing either a long linear alkyl chain (dodecyl) or a tocopherol moiety. Ketoconazole was used as model for hydrophobic drugs. Comparison of the drug loading with PEG-b-PPE bearing shorter pendant groups is reported evidencing the key role of the structure of the pendant group on the PPE backbone. Finally, a first evidence of the biocompatibility of these novel PEG-b-PPE copolymers was achieved by performing cytotoxicity tests. The PEG-b-PPE derived by tocopherol was evidenced as particularly promising as delivery system of poorly water-soluble drugs.

Atmospheric pressure cold plasma versus wet-chemical surface treatments for carboxyl functionalization of polylactic acid: A first step toward covalent immobilization of bioactive molecules.

The use of polylactic acid (PLA) has attracted growing interest, particularly in recent years, for biomedical applications because of its mechanical properties, biocompatibility, and biodegradability. Despite this, features such as surface hydrophobicity and the absence of suitable functional groups for covalent immobilization of bioactive molecules, make it challenging to endow PLA-based medical devices with additional features and thus broaden their range of applicability. In the present study, we demonstrate the suitability of atmospheric pressure dielectric barrier discharges operating in the Townsend regime as a promising alternative to other surface treatments, such as diazonium and alkali hydrolytic treatments, for carboxyl functionalization of PLA. Chemical changes in PLA surfaces are evaluated by contact angle measurements and by X-ray photoelectron spectroscopy while physical changes are investigated by scanning electron microscopy and atomic force microscopy. The amount of carboxyl groups generated on PLA surfaces is assessed by toluidine blue O assay and substantiated by grafting, through carboxyl groups, a fluorescent probe containing amino functionalities. All of the surface treatments have proven to be very effective in generating carboxylic groups on the PLA surface. Nevertheless, plasma treatment is shown to not degrade the PLA surface, in sharp contrast with diazonium and alkali hydrolytic treatments.

Effect of linking arm hydrophilic/hydrophobic nature, length and end-group on the conformation and the RGD accessibility of surface-immobilized fibronectin.

In order to stimulate the cellular response to implant materials, extracellular matrix (ECM) proteins, such as collagen and fibronectin (FN), are immobilized on the implant surface. Amongst all ECM proteins used for biomimetic materials for medical applications, FN is one of the most investigated proteins thanks to its ability to promote cell adhesion and its contribution to important physiological processes. However, its conformation and hence its bioactivity strongly depend on the hydrophilic/hydrophobic nature of the surface as well as on immobilization strategies. This work investigates the effect of these two parameters, as well as the effect of the crosslinker length. FN was grafted onto silicon wafers using eights different linking arms presenting different lengths, hydrophilic/hydrophobic characters and binding sites. The protein was linked through either its amino groups (lysine amino acids) or sulfhydryl functionalities (cysteine amino acids). The grafting of each crosslinker and subsequent FN conjugation onto the surfaces was evidenced by X-ray photoelectron spectroscopy, while the surface hydrophilicity was determined by contact angle measurements. Moreover, atomic force microscopy images revealed that the conformation of surface conjugated FN only depends on the hydrophilicity of the linking arm. The FN conformation was also probed by enzyme-linked immunosorbent assays (ELISA). ELISA data demonstrated that all of the three investigated parameters linking arm parameter (length, hydrophobic/hydrophilic character, and terminal end-group) somewhat influence the RGD accessibility.

Preparation and characterisation of flame retardant encapsulated with functionalised silica-based shell.

Intumescent fire retardant (IFR) coatings are nowadays considered as the most effective flame retardant (FR) treatment. Nevertheless, the principal compound in an IFR system, ammonium polyphosphate (APP), is highly sensitive to moisture and IFR coating effectiveness decreases quickly. The main objective of this study is to encapsulate APP in a hybrid silica-based membrane by sol-gel process using alkoxysilane tetraethoxysilane (TEOS) and methyltriethoxysilane (MTES) precursor. The morphology and structure of APP and microencapsulated ammonium polyphosphate (MAPP) were assessed by scanning electron microscopy and Fourier transforms infrared spectroscopy (FTIR). X-ray photoelectron spectroscopy (XPS) results revealed that APP was well encapsulated inside the polysiloxane shells. The thermal degradation of APP and MAPP was evaluated by thermogravimetric analysis. At 800 °C, the MAPP had higher char residue (70.49 wt%) than APP (3.06 wt%). The hydrophobicity of MAPP increased significantly with the water contact angles up to 98°, in comparison to 20° for APP.

Development and evaluation of injectable nanosized drug delivery systems for apigenin.

The purpose of this study was to develop different injectable nanosized drug delivery systems (NDDSs) i.e. liposome, lipid nanocapsule (LNC) and polymeric nanocapsule (PNC) encapsulating apigenin (AG) and compare their characteristics to identify the nanovector(s) that can deliver the largest quantity of AG while being biocompatible. Two liposomes with different surface characteristics (cationic and anionic), a LNC and a PNC were prepared. A novel tocopherol modified poly(ethylene glycol)-b-polyphosphate block-copolymer was used for the first time for the PNC preparation. The NDDSs were compared by their physicochemical characteristics, AG release, storage stability, stability in serum, complement consumption and toxicity against a human macrovascular endothelial cell line (EAhy926). The diameter and surface charge of the NDDSs were comparable with previously reported injectable nanocarriers. The NDDSs showed good encapsulation efficiency and drug loading. Moreover, the NDDSs were stable during storage and in fetal bovine serum for extended periods, showed low complement consumption and were non-toxic to EAhy926 cells up to high concentrations. Therefore, they can be considered as potential injectable nanocarriers of AG. Due to less pronounced burst effect and extended release characteristics, the nanocapsules could be favorable approaches for achieving prolonged pharmacological activity of AG using injectable NDDS.