Papers by Keyword: Bisphosphonate

Abstract: Two β,γ-CX₂-5-bromouridine triphosphates (X = F and Cl) have been efficiently obtained from 5-bromouridine 5′-phosphoropieridate via the activation of the P(V)-N bond with 4,5-dicyanoimidazole.

Abstract: The possibility to develop a bone implant with bioactive aspects and in situ drug-delivery properties, in order to provide local treatment in vivo, is a big challenge. Where conventional surface modifications for bone implants focused on the deposition of ceramic (mostly calcium phosphate, CaP) coatings, current surface engineering approaches attempt to incorporate active features to render bone implant surfaces capable to direct biological performance. Biomimetic apatite nanocrystals (nAp) represent, among the CaPs, an elective material for bone applications and their surface functionalization with drugs allows them to act as a drug-delivery vehicle. Since load-bearing bone implants are increasingly used in patients with compromised health conditions, surface engineering is important to warrant the performance of these implants under such conditions. In view of this, bisphosphonates (BPs) represent a treatment modality for a variety of disorders of bone metabolism associated to bone loss, including Paget's bone disease, osteoporosis, fibrous dysplasia and bone metastases. In this work, we have synthesized and characterized bioinspired nAp and evaluated their functionalization with alendronate. In vitro tests will be used to evaluate the efficacy of the functionalized compound to impede the formation of osteoclasts and to show that alendronate-functionalized nAp can significantly reduce osteoclasteogenesis. Finally, alendronate-functionalized nAp (FnAp) has been deposited on titanium implants via the electrospray deposition technique in order to develop inorganic-organic coatings for bone implants with improved functionality.

Abstract: Two methods of loading bisphosphonate (BP) into hydroxylapatite (HA) coatings on crystalline TiO2 surfaces were investigated to improve bone ingrowth to implant surfaces. In the study the BP pamidronate was used. Ti-plates coated with crystalline TiO2 were soaked in phosphate buffer saline (PBS) for 7 days at 40° C and thereafter soaked in solutions of BP, 0.5 mg/ml for 15 or 60 minutes (fast loading method). In the second method BP was dissolved into PBS in different concentrations before immersion of the discs for 7 days (co-precipitation method). Surface and bulk were analysed using electron spectroscopy for chemical analysis, scanning electron microscope and x-ray diffraction. Release of BP was studied using alternating ionic current method. It was shown that fast loading by soaking in a BP solution for 15 minutes was sufficient to load BP into a HA coating. Co-precipitation showed that a thin layer of calcium phosphate crystals containing BP can be deposited directly onto a crystalline TiO2 surface.

Abstract: In the present study sodium clodronate, a well known therapeutic agent from the family of bisphosphonates (BP) was incorporated in an apatite coating, previously formed on the surface of a starch based biomaterial by a sodium silicate methodology, as a strategy to develop a site-specific drug delivery system for bone tissue regeneration. The effects on the resulting apatite coatings were evaluated in terms of morphology, chemistry and structure. As a preliminary approach, this first study aimed at evaluating also the effects of this BP on the viability, growth and function of a human osteoblast cell line, since there is still little information available on the interaction between BPs and this type of cells.

Abstract: One type of potent aminobisphosphonate (Zoledronate) has been chemically associated onto b-tricalcium phosphate [b-TCP] and calcium deficients apatite [CDA]. Two different association modes have been observed, according to the nature of the Calcium Phosphate [CaP] support and/or the initial concentration of the Zoledronate solution. b-TCP appears to promote Zoledronate-containing crystals formation. On the other hand, at concentrations < 0.05 mol.L-1 CDA seems to undergo chemisorption of the drug through a surface adsorption process, due to PO3 for PO4 exchange, which is well described by Freundlich equations. At concentrations > 0.05 mol.L-1, crystalline needles of a Zoledronate complex form onto the CDA surface. The ability of CDA to release Zoledronate, resulting in the inhibition of osteoclastic activity, was shown using a specific in vitro bone resorption model.