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    Characterization and Evaluation of Triamcinolone, Raloxifene, and Their Dual-Loaded Microspheres as Prospective Local Treatment System in Rheumatic Rat Joints
    (Elsevier Science Inc, 2014) Ocal, Yigit; Kurum, Baris; Karahan, Siyami; Tezcaner, Aysen; Ozen, Seza; Keskin, Dilek
    In this study, injectable microspheres were developed for the local treatment of joint degeneration in rheumatoid arthritis (RA). Microspheres loaded with triamcinolone (TA), a corticosteroid drug, and/or raloxifene (Ral), a cartilage regenerative drug, were prepared with a biodegradable and biocompatible polymer, polycaprolactone (PCL). Microspheres were optimized for particle size, structural properties, drug release, and loading properties. In vitro release of Ral was very slow because of the low solubility of the drug and hydrophobic nature of PCL. However, when coloaded with TA, both drugs were released at higher amounts compared with their single forms. Smallest particle sizes were obtained in dual drug-loaded microspheres. In vitro cytotoxicity tests showed biocompatibility of microspheres. In vivo bioefficacy of these microspheres was also examined in adjuvant-induced arthritis model in rats. In vivo histological studies of control groups showed development of RA with high median lesion score (5.0). Compared with control and intra-articular free drug injections, microsphere treatment groups showed lower lesion scores and better healing outcomes in histological evaluations. Results suggest that a controlled delivery system of TA and RAL by a single injection in inflamed joints holds promise for healing and suppressing inflammation. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2396-2405, 2014
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    Effects of the doping concentration of boron on physicochemical, mechanical, and biological properties of hydroxyapatite
    (Elsevier Sci Ltd, 2022) Jodati, Hossein; Tezcaner, Aysen; Alshemary, Ammar Z.; Sahin, Volkan; Evis, Zafer
    Ion doping is an approach to modify properties of materials, like hydroxyapatite (HA), that contributes to designing biomaterials with desired characteristics applicable in bone defect treatments. Recently, boron (B) has been noticed in biomaterial fields due to its beneficial effects on formation, growth, and quality of bone. In this study, B-doped HA nanoparticles with different molar concentrations of B (0.05, 0.1, 0.25, and 0.5) were synthesized through microwave-assisted wet precipitation. The effects of B content on various properties of HA were evaluated. The results demonstrated that the size of HA particles reduced from 106 nm to 89-85 nm in B doped materials. Meanwhile, the crystallinity degree of B doped HA (BHA) samples was between 89.90% and 93.77%, compared to 95.19% of HA. Diametral tensile strength of samples was measured in the ranges of 2.51 and 3.61 with no significant difference among groups. The micro-hardness of HA was 0.88 GPa, whilst doped ones had hardness values of 0.5 GPa-0.68 GPa. Biodegradability of samples increased from less than 1% to approximately 4% after 28 days, while B-doping did not make any change in the degradation rate. Doping dosages were appropriate in terms of bioactivity and cell viability, and B doping caused higher bioactivity and cell proliferation. All changed properties were dose-dependent and more effective in doped groups with a higher amount of B. Despite proliferative effect, <= 260 mu g/l and 770 mu g/l of B release in two groups with the highest dopant concentrations did not positively influence the osteogenic activity of cells. Our results demonstrated that doping concentrations that resulted in B release & LE;260 mu g/l seem more appropriate dosage, especially for bone tissue engineering and substitute applications due to promoted bioactivity and proliferation, as well as no obstructive effects on mechanical properties and osteogenic activities of HA.