Hybrid Mineral/Organic Material Induces Bone Bridging and Bone Volume Augmentation in Rat Calvarial Critical Size Defects.

In craniofacial bone defects, the promotion of bone volume augmentation remains a challenge. Finding strategies for bone regeneration such as combining resorbable minerals with organic polymers would contribute to solving the bone volume roadblock. Here, dicalcium phosphate dihydrate, chitosan and hyaluronic acid were used to functionalize a bone-side collagen membrane. Despite an increase in the release of inflammatory mediators by human circulating monocytes, the in vivo implantation of the functionalized membrane allowed the repair of a critical-sized defect in a calvaria rat model with de novo bone exhibiting physiological matrix composition and structural organization. Microtomography, histological and Raman analysis combined with nanoindentation testing revealed an increase in bone volume in the presence of the functionalized membrane and the formation of woven bone after eight weeks of implantation; these data showed the potential of dicalcium phosphate dihydrate, chitosan and hyaluronic acid to induce an efficient repair of critical-sized bone defects and establish the importance of thorough multi-scale characterization in assessing biomaterial outcomes in animal models.

Etoposide encapsulation in surface-modified poly(lactide-co-glycolide) nanoparticles strongly enhances glioma antitumor efficiency.

Etoposide (VP-16) is a hydrophobic anticancer agent inhibiting Topoisomerase II, commonly used in pediatric brain chemotherapeutic schemes as mildly toxic. Unfortunately, despite its appropriate solubilization in vehicle solvents, its poor bioavailability and limited passage of the blood-brain barrier concur to disappointing results requiring the development of new delivery system forms. In this study, etoposide formulated as a parenteral injectable solution (Teva®) was loaded into all-biocompatible poly(lactide-co-glycolide) (PLGA) or PLGA/P188-blended nanoparticles (size 110-130 nm) using a fully biocompatible nanoprecipitation technique. The presence of coprecipitated P188 on encapsulation efficacies and in vitro drug release was investigated. Drug encapsulation was determined using HPLC. Inflammatory response was checked by FACS analysis on human monocytes. Cytotoxic activity of the various simple (Teva®) or double (Teva®-loaded NPs) formulations was studied on the murine C6 and F98 cell lines. Obtained results suggest that, although noninflammatory neither nontoxic by themselves, the use of PLGA and PLGA/P188 nanoencapsulations over pre-existing etoposide formulation could induce a greatly improved cytotoxic activity. This approach demonstrated a promising perspective for parenteral delivery of VP16 and potential development of a therapeutic entity.

Bifunctional polypyridyl-Ru(II) complex grafted onto gadolinium-based nanoparticles for MR-imaging and photodynamic therapy.

The synthesis, optical properties and efficiency of new multifunctional nanoparticles as theranostic (fluorescence/MRI/PDT) agents are described. They are based on a polysiloxane network and surrounded by gadolinium(III) chelates and ruthenium(II) complexes. The size of the nanoparticles is maintained under 5 nm in order to permit their efficient elimination from the body. Their potential use as a theranostic agent (PDT/MRI) is described. The magnetic properties of the nanoparticles are studied by relaxometry (r1 = 9.21 mM(-1) s(-1) at 40 MHz; r2/r1 = 1.14) and the signal enhancement is validated by the acquisition of phantoms on a 3 T MRI imager. The therapeutic potential for photodynamic therapy of the nanoparticles has been studied in vitro on HEK293 cells and an effective quantum yield of 0.33 for (1)O2 production has been determined in deuterated water.