Interaction of Ceramic Implant Materials with Immune System.

The immuno-compatibility of implant materials is a key issue for both initial and long-term implant integration. Ceramic implants have several advantages that make them highly promising for long-term medical solutions. These beneficial characteristics include such things as the material availability, possibility to manufacture various shapes and surface structures, osteo-inductivity and osteo-conductivity, low level of corrosion and general biocompatibility. The immuno-compatibility of an implant essentially depends on the interaction with local resident immune cells and, first of all, macrophages. However, in the case of ceramics, these interactions are insufficiently understood and require intensive experimental examinations. Our review summarizes the state of the art in variants of ceramic implants: mechanical properties, different chemical modifications of the basic material, surface structures and modifications, implant shapes and porosity. We collected the available information about the interaction of ceramics with the immune system and highlighted the studies that reported ceramic-specific local or systemic effects on the immune system. We disclosed the gaps in knowledge and outlined the perspectives for the identification to ceramic-specific interactions with the immune system using advanced quantitative technologies. We discussed the approaches for ceramic implant modification and pointed out the need for data integration using mathematic modelling of the multiple ceramic implant characteristics and their contribution for long-term implant bio- and immuno-compatibility.

Clarithromycin as a chiral selector for enantioseparation of basic compounds in nonaqueous capillary electrophoresis.

The first use of macrolide antibiotic clarithromycin (CLM) in nonaqueous media for enantioseparation (partial or baseline) of the following compounds: alprenolol, atenolol, metoprolol, clenbuterol, methoxyphenamine, pindolol, propranolol, sotalol, synephrine, labetalol, and fenoterol is reported. Each analysis took less than 15 min. To find optimal separation conditions, some properties of CLM (adsorption, solubility), as well as the effect of experimental parameters on the enantioseparation of analytes (background electrolyte composition, chiral selector concentration, temperature, and applied voltage) were studied. The best chiral resolution was achieved in methanolic solution of 100 mM citric acid, 10 mM NaOH, 240-300 mM H3 BO3 , and 60-75 mM CLM. Using the proposed procedure, adsorption of CLM on the capillary wall was negligible and the repeatability of the migration times (RSD) was as good as 1.6%. For the analysis of propranolol, the linearity was achieved in the concentration range 2.5 × 10(-2) - 3.0 × 10(-1) mg/mL with the LODs (3 × S/N) being equal 2.6 × 10(-3) mg/mL and 2.8 × 10(-3) mg/mL for the first and the second enantiomers, respectively. Linear range for metoprolol enantiomers was 1.0 × 10(-2) -1.6 × 10(-1) mg/mL. The LODs (3 × S/N) were determined as 2.8 × 10(-3) and 3.0 × 10(-3) mg/mL for the first and the second enantiomers, respectively.

Enantioseparation of organic acids of pharmaceutical interest using eremomycin as a chiral selector.

Strong adsorption of eremomycin on the fused-silica capillary wall was used for separation of enantiomers by CE. The capillary with adsorbed chiral selector was shown to be easily prepared and has reproducible properties. The effect of the chiral selector concentration, pH and composition of the BGE, and applied voltage on enantioseparation of acidic compounds, such as profens and aromatic carboxylic acids, was investigated. Two native α-amino acids, aspartic acid and glutamic acid, were enantioseparated. Fourteen tested compounds (including amino acids) were baseline resolved. Good selectivity of separation (α>1.09) was achieved. The migration order of ibuprofen and ketoprofen enantiomers was determined. The procedures were proposed for the analysis of flurbiprofen and warfarin in pharmaceuticals. Linearity was achieved in the concentration range of 4.0×10(-5)-2.0×10(-3) M for flurbiprofen and 3.2×10(-6)-4.9×10(-6) M for warfarin. The detection limits were found to be about 1×10(-5) M for flurbiprofen and 1×10(-6) M for warfarin.

Bovine serum albumin adsorbed on eremomycin and grafted on silica as new mixed-binary chiral sorbent for improved enantioseparation of drugs.

A new silica-based, mixed-binary chiral sorbent grafted with the macrocyclic antibiotic eremomycin and bovine serum albumin (BSA) was obtained. The sorbent-filled high-performance liquid chromatography column was capable of enantioseparation of racemic drugs, such as profens, in reversed-phase-chromatography mode. The mixed-binary eremomycin-BSA-sorbent showed better capability for profens enantioseparation as compared with a sorbent containing eremomycin only. BSA grafted onto the sorbent surface significantly reduced retention times of other proteins from the analyte solution, and free proteins (including BSA) injected as analytes were not retained on the column, and subsequently eluted with a dead volume. The drastic difference observed in the binding of profens and other proteins using the sorbent was tested for determination and enantioseparation of profens in artificial-urine solutions.

Chiral analysis of pharmaceuticals by capillary electrophoresis using antibiotics as chiral selectors.

The review summarizes the use of the chiral capillary electrophoresis (CE) with different class of antibiotics as chiral selectors in the pharmaceutical field. Basic factors influencing the enantioseparation are shortly discussed. Non-aqueous capillary electrophoresis is also included as well as the coupling of CE to MS. The selection of a chiral selector according the ionic state and structure of the analyte is described. Summary of pharmaceutical applications of chiral CE is given.

Enantiorecognition of profens by capillary electrophoresis using a novel chiral selector eremomycin.

The evaluation of a macrocyclic glycopeptide antibiotic, eremomycin, as a chiral selector in capillary electrophoresis (CE) has been performed. The stability of eremomycin in solution and capillary electrolyte, as well as its optical and electrophoretic properties have been discussed. The effect of experimental parameters influencing the enantioseparation of several profens has been studied. Excellent enantioseparation of profens has been achieved and migration order has been validated. Comparison of enantioseparations of profens in CE by using eremomycin-mediated electrolytes and in HPLC with eremomycin immobilized on silica has revealed similar trends for both methods.

Heptakis(6-amino-6-deoxy)-beta-cyclodextrin as a chiral selector for the separation of anionic analyte enantiomers by capillary electrophoresis.

A hepta-substituted beta-cyclodextrin bearing seven amino groups, heptakis(6-amino-6-deoxy)-beta-cyclodextrin (per-6-NH2-beta-CD) was successfully used as a chiral selector for the enantioseparation of different anionic analytes. The running buffer pH and chiral selector concentration were the studied parameters crucial in achieving the maximum possible enantioresolution. Enantiomeric separation of a mixture of seven carboxybenzyl-amino acids was achieved in 24 min. Excellent resolution was obtained for carboxybenzyl-tryptophan (Rs = 11.2).