Elution Characteristics Research Articles

Does Antibiotic Elution From PMMA Beads Deteriorate after 1-year Shelf Storage?

Antibiotic-impregnated polymethylmethacrylate beads are widely used as an adjunct in the treatment of orthopaedic infections. Because there is no commercially available bead in the United States, surgeons must manufacture bead sets at the time of implantation. This can be time consuming and wasteful. We hypothesized antibiotic-impregnated beads would maintain consistent elution for up to 1 year after manufacturing and storage. Tobramycin-impregnated antibiotic beads were manufactured using a bead mold. The antibiotic was either hand-mixed into the polymethylmethacrylate powder (1.2 g/40 g) or came premixed from the factory (1 g/40 g). Packages of beads were gas-sterilized and stored at room temperature. Beads were tested at 0, 1, 2, 3, 6, and 12 months. Antibiotic levels in the eluent from each day of the month were measured. We were unable to detect any difference in the amount of antibiotic elution between beads tested immediately after manufacture and beads manufactured and stored for 6 or 12 months. Beads with hand-mixed antibiotics eluted higher levels of antibiotics than the beads prepared with factory-mixed antibiotics. We conclude antibiotic beads can be made, sterilized, and used after 1 year of storage with no deleterious effect on antibiotic elution characteristics.

The AviD-tag, a NeutrAvidin/avidin specific peptide affinity tag for the immobilization and purification of recombinant proteins

The widespread success of affinity tags throughout the biological sciences has prompted interest in developing new and convenient labeling strategies. Affinity tags are well-established tools for recombinant protein immobilization and purification. More recently these tags have been utilized for selective biological targeting towards multiplexed protein detection in numerous imaging applications as well as for drug-delivery. Recently, we discovered a phage-display selected cyclic peptide motif that was shown to bind selectively to NeutrAvidin and avidin but not to the structurally similar streptavidin. Here, we have exploited this selectivity to develop an affinity tag based on the evolved DRATPY moiety that is orthogonal to known Strep-tag technologies. As proof of principle, the divalent AviD-tag ( Avidin-Di-tag) was expressed as a Green Fluorescent Protein variant conjugate and exhibited superior immobilization and elution characteristics to the first generation Strep-tag and a monovalent DRATPY GFP-fusion protein analogue. Additionally, we demonstrate the potential for a peptide based orthogonal labeling strategy involving our divalent AviD-tag in concert with existing streptavidin-based affinity reagents. We believe the AviD-tag and its unique recognition properties will provide researchers with a useful new affinity reagent and tool for a variety of applications in the biological and chemical sciences.

In-situ graft-polymerization preparation of cation-exchange supermacroporous cryogel with sulfo groups in glass columns

Graft polymerization of monomer chains with expected functional groups onto the matrix pore surfaces by initiator is an effective approach for introducing ion-exchange groups to cryogel matrix to get anion- or cation-exchange supermacroporous cryogels. In this work, a novel cation-exchange cryogel with sulfo binding groups was prepared by grafting of 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPSA) onto polyacrylamide-based cryogels in glass columns. The grafting polymerization was achieved in an in-situ manner which was performed by pumping the initiator and the reactive solution of graft monomer with sulfo binding groups directly through a cryogel bed pre-produced in a glass column under frozen condition. The axial liquid dispersion characteristics within the monolithic cryogel beds before and after the in-situ polymerization were compared by measuring residence time distributions (RTDs) at various liquid flow rates using tracer pulse-response method. Microstructure morphology of pores within cryogels was analyzed by scanning electron microscopy (SEM). Chromatography of lysozyme was carried out to reveal the protein breakthrough and elution characteristics in the obtained cryogel beds.

In Vitro Elution Studies of Amikacin and Cefazolin from Polymethylmethacrylate

To compare the in vitro elution characteristics of amikacin and cefazolin from polymethylmethacrylate (PMMA) alone and in combination. A prospective, controlled, experimental study. Three aliquots of 6 g sterile PMMA were measured and to them added (1) 750 mg amikacin; (2) 1050 mg cefazolin; and (3) 750 mg amikacin and 1050 mg cefazolin. Ten beads of each antimicrobial/PMMA combination were placed in 5 mL phosphate-buffered saline (PBS) at pH 7.4 and room temperature with constant agitation. PBS was sampled at 15 time points between 1 hour and 30 days. Amikacin concentrations were determined by fluorescence polarization immunoassay and cefazolin concentrations by high-performance liquid chromatography. Amikacin and cefazolin eluted at concentrations greater than 8 and 4 times, respectively, above the minimum inhibitory concentration (MIC) for susceptible bacteria over 30 days. Co-elution of the antibiotics resulted in a greater rate and proportion of antibiotic eluted. Concentrations of amikacin and cefazolin in the co-eluted fluid were not maintained sufficiently above the MIC for selected bacteria over 30 days. PMMA beads of only amikacin or cefazolin-eluted concentrations greater than the MIC for selected bacteria for 30 days. Co-elution of the antibiotics at the selected doses resulted in a significantly shorter duration of elution and may not be effective for treatment of wound infection. Co-elution of amikacin and cefazolin from PMMA at the selected doses cannot be recommended for sustained treatment of infection.

Elution characteristics and mechanical properties of calcium sulfate-loaded bone cement containing teicoplanin

BackgroundAcrylic bone cement is the most widely used drug delivery system clinically. It has already been shown that antibiotic release is significantly increased when calcium sulfate-loaded acrylic bone cement is used. However, there is no information yet about the mechanical responses of these composite materials. Thus, the purpose of this study was to investigate the effect of calcium sulfate on the elution characteristics and mechanical behavior of teicoplanin-loaded acrylic bone cement. MethodsFour groups of acrylic bone cements (GI, GII, GIII, GIV) were prepared using the same liquid/powder ratios. After mixing, the bone cement and additive mixtures were packed into different-type molds to prepare the specimens for the elution and mechanical tests. All of the specimens were tested for two conditions (dry and human plasma solution). The mechanical tests included the setting time (hardness) and tensile, bending, and compression strengths. The fracture surfaces of the failed samples were also examined by scanning electron microscopy. ResultsTeicoplanin release in the calcium sulfate powder added groups (GIII and GIV) was higher than that of GII. When the calcium sulfate and teicoplanin were added on acrylic bone cement, the compressive, bending and tensile strength, hardness values, and elastic modulus decreased. Also, further reductions were evident in human plasma solution. ConclusionsAlthough mechanical properties of tested specimens decreased, all of the results obtained were higher than those required by the American Society for Testing and Materials Standards, but further investigations are necessary before making definitive statements for clinical applications.

Effects of porcine small intestinal submucosa on elution characteristics of gentamicin-impregnated plaster of Paris

To evaluate effects of small intestinal submucosa (SIS) on elution properties of plaster of Paris (POP). 27 POP cylinders, 27 POP spheres, and 9 polymethylmethacrylate (PMMA) spheres. Pellets were loaded with gentamicin (50 mg/g) and divided into 7 groups of 9 beads each: PMMA spheres; POP cylinders coated with 0, 4, or 8 layers of SIS; and POP spheres coated with 0, 4, or 8 layers of SIS. Gentamicin concentration was measured 6, 12, 18, 24, 32, 40, and 48 hours and 3, 4, 5, 7, 14, 21, 28, 35, and 42 days after wrapping. Porosity was evaluated via scanning electron microscopy. Curvature factor of elution curves, total amount of drug released (TDR), time required to reach 50% of total release (TDR(t50)), and number of days with concentrations > or = 1 microg/mL were compared among groups. SIS decreased the curvature factor and increased the TDR(t50) and TDR of POP spheres and cylinders. Curvature factor of the PMMA-release curve remained lower than that for any POP group, but all POP groups wrapped in SIS released more gentamicin than PMMA spheres. Gentamicin concentrations remained > or = 1 microg/mL in SIS-wrapped POP and PMMA groups throughout the study. Wrapping POP in SIS minimized the increase in porosity of pellets. Wrapping POP with SIS slows the release and increases the amount of gentamicin leaching from spheres and cylinders. All groups wrapped in SIS maintained antimicrobial concentrations greater than the minimum inhibitory concentration of most pathogens.

Radioactive Waste Incineration-Ash Pellets Sintered with Borosilicate Glass

In Japan, low-level radioactive wastes discarded by research institutions and hospitals are packed into containers and stored. Volume reduction by incineration and compression processing are sometimes attempted; alternatively, the wastes are left in an unprocessed state because neither landfill sites nor disposal methods have been established. Especially, low-level radioactive waste incineration ash presents great problems of security, safety, and stability in inventory location. A safe and appropriate disposal processing method is desired because the bulk density of ash is low; the ash is also easily dispersed. Volume reduction and stabilization for low-level radioactive waste incineration ash were verified for low-temperature sintering method using glass bottle cullet. The proposed method was useful for easy treatment of low-level radioactive waste incineration ash. This report describes the difference between soda lime glass (cullet) and borosilicate glass for the RI ash sintering, and characteristics of RI volatilization and elution from the sintered radioactive waste pellets. The borosilicate glass is used for glass melt solidification of high-level radioactive waste.

The Influence of Antibiotics on the Fatigue Life of Acrylic Bone Cement

Aseptic loosening attributed to cement fracture and subsequent disruption of fixation interfaces remains a major long-term mode of failure of arthroplasties performed with cement1 (Fig. 1). The fracture strength of bone cement, especially in fatigue, is an important indicator of cement integrity and the potential for fixation failure. In current practice, orthopaedic surgeons may choose to utilize antibiotics in bone cement for prophylaxis or treatment of a known infection. However, the antibiotics, bone cement, and mixing method employed lead to variability in the quality of the end product2-5. To date, several United States orthopaedic manufacturers have received Food and Drug Administration (FDA) 510(k) clearance for use of their prepackaged antibiotic-loaded bone cement for the second stage of a two-stage revision after the initial infection has been eradicated. This availability provides a more uniform cement mix with known mechanical and elution characteristics at the level of 0.5 to 1.0 g of antibiotic per 40 g of polymer powder. In this study, we evaluated the influence of antibiotic inclusion on the porosity, strength, and fatigue life of six contemporary bone cements. Six surgical quality and commercially available surgical bone cements were evaluated: Endurance and Endurance Gentamicin (DePuy Orthopaedics, Warsaw, Indiana), Surgical Simplex P and Simplex P with Tobramycin (Stryker Orthopaedics, Mahwah, New Jersey), and VersaBond and VersaBond AB with Gentamicin (Smith and Nephew, Memphis, Tennessee). Ten 1.2-g doses of Tobramycin for Injection USP (United States Pharmacopeia) (Pharma-Tek, Huntington, New York), which is the base quantity supplied to the operating theater when antibiotics are hand-mixed with bone cement, were acquired. Three vacuum-mixing systems (Figs. 2-A, 2-B, and 2-C)—the Cemvac (DePuy Orthopaedics), the ACM (Advanced Cement Mixing System; Stryker), and the Vortex (Smith and Nephew)—were acquired directly from their manufacturers. Nine study samples were created: hand-mixed …

Simultaneous separation of nitrofuran antibiotics and their metabolites by using micellar electrokinetic capillary chromatography

Mixtures comprising nitrofuran antibiotics (NFA) and nitrofuran metabolites (NFM) were resolved for the first time by using MEKC. Sodium deoxycholate (SDC) was chosen as the micelle-forming surfactant. Optimization of separation conditions was achieved by using a central composite experimental design (CCD) approach. Experimental parameters such as concentration ratio of borate to phosphate in the buffer, pH of the running electrolyte and voltage were investigated. The effect of concentration of the surfactant on resolution was significant. Under optimal conditions of 80 mM SDC, pH 9.0, (20 mM borate + 20 mM phosphate) and 16 kV, the resolution between eight consecutive peak pairs ranged from 1.9 to 11.8. Due to the absence of a UV-active chromophore in the metabolites, they were derivatized with 2-nitrobenzaldehyde (2-NBA). In order to mimic a proposed extraction procedure for the analysis of both NFA and/or derivatized NFM in a sample, aqueous samples (prederivatized with 2-NBA) were extracted by using C(18) SPE cartridges. After washing with H(2)O, the cartridges were eluted with a small portion of organic solvent with weak elution characteristics to remove excess 2-NBA (hexane was chosen). Target analytes were then recovered with ACN. Excellent reproducibility of migration time (t(mig)) was achieved for all analytes using the developed MECC approach, with absolute t(mig) <1% RSD and t(mig) ratio <0.2% RSD, and peak area ratio was 4% RSD. The LOD for each compound, calculated by extrapolating to an S/N of 3, were found to be 0.19-2.0 microg/mL.

Evaluation of Elution Parameters for Cesium Ion Exchange Resins

Cesium ion exchange is one of the planned processes for treating and disposing of waste at the U.S. Department of Energy Hanford Site. Radioactive supernatant liquids from the waste tanks will undergo ultrafiltration, followed by cesium ion exchange using a regenerable organic ion exchange resin. Two resins, SuperLig®644 and a resorcinol‐formaldehyde resin, are being evaluated for cesium removal and cesium elution characteristics. The main purpose of this study is to optimize the cesium elution to provide a resin that, after undergoing elution, would meet the U.S. Department of Energy/Office of River Protection Project‐Waste Treatment Plant processing and resin disposal criteria. Columns of each resin type were loaded to greater or equal to 90% breakthrough with a Hanford waste stimulant and eluted with nitric acid. The temperature, flow rate, and nitric acid concentration were varied to determine the optimal elution conditions. Temperature and eluant flow rate were the most important elution parameters. As would be predicted based upon kinetic consideration alone, decreasing the eluant flow rate and increasing the temperature provided the optimal elution conditions. Varying the nitric acid concentration did not have a significant effect on the elution completion; however, elutions performed using both high acid concentration (1 M) and elevated temperature (45°C) resulted in resin degradation, causing gas generation and resin bed disruption.

Preparation of uniform biodegradable microparticles using laser ablation

In an attempt to prepare uniformly sized biodegradable microparticles for controllable drug eluting and targeting characteristics, a novel technique by employing ultrashort pulse (USP) laser has been developed. This method involves pumping a drug–polymer solution through a small orifice creating a liquid stream. A USP laser constantly fires at the stream to cut it into discrete droplets and consequently solid particles can be obtained with monodisperse size distribution. Through mathematical modeling, volumetric flow rate, orifice size, laser spot size, and laser frequency were found as sole factors determining the size profile of the resulting microparticles. By choosing appropriate set of variables, monosized biodegradable microparticles with wide range of particle size may be prepared.

Gas-Liquid Chromatographic Study of Thermodynamics of Some Alkanes on Polysiloxane Stationary Phase

A gas-liquid chromatographic study of the interaction and elution characteristics of 47 paraffinic compounds from C5-C14 normal, branched, and cyclic alkanes using 100% dimethyl polysiloxane and 35% diphenyl, 65% dimethyl polysiloxane as stationary phases is reported. It is shown that polysiloxane stationary phase in capillary column gas chromatography possesses excellent chromatographic properties and is unique in the separation of iso-paraffins. The mechanism, retention, and selectivity are discussed by measuring various thermodynamic parameters: the enthalpy of solution Δ H, the entropy of solution Δ S, and the free energy Δ G.

Safeness of Simplex-Tobramycin Bone Cement in Patients with Renal Dysfunction Undergoing Total Hip Replacement

To compare the pharmacokinetic profile of tobramycin in blood, urine, and at the operative site following the use of Simplex-tobramycin bone cement in primary total hip replacement between patients with and without renal dysfunction. Six patients with renal dysfunction underwent cemented primary total hip replacement for osteoarthritis. The elution characteristics of Simplex-tobramycin bone cement in the 6 patients with renal dysfunction were compared with 9 patients who had normal renal function. Blood, urine, and drainage fluid specimens were collected for 72 hours postoperatively. Very high concentrations of tobramycin were seen in the drainage fluid of the 2 groups. Mean serum tobramycin levels peaked at postoperative 3 hours, and declined rapidly to negligible levels at 72 hours in both groups. Mean urinary tobramycin concentrations peaked at postoperative 12 hours and declined rapidly until 48 hours in both groups. Urinary tobramycin was excreted significantly more slowly in renal dysfunction group in the first 12 hours, but not thereafter. Although serum creatinine levels of the renal dysfunction group were higher throughout the study period, the difference was not significant. Both groups achieved excellent local delivery of the antibiotic with minimal systemic concentrations. Simplex-tobramycin bone cement appears to be an effective and safe means to deliver antibiotic for patients with renal dysfunction who undergo total hip replacement.

Ghrelin in plants: What is the function of an appetite hormone in plants?

In the present work, we provide compelling evidence for the expression of a ghrelin-like peptide hormone that has only been associated with animals, in various plant tissues. Ghrelin, the appetite stimulating hormone, has been identified from a number of different species including humans, rat, pig, mouse, gerbil, eel, goldfish, bullfrog and chicken. The study here was conducted using an immunohistochemistry assay to screen whether plants have any ghrelin immunoreactivity. In this respect, Prunus x domestica L . and Marus alba were examined. Immunohistochemistry results showed that there is a strong human ghrelin immunoreactivity substance in the parenchyma cells of these plants. This was entirely unexpected since this hormone was considered to be present solely in animals. Thus, this study is the first to report the presence of a peptide with ghrelin-like activity in plants, a finding that has only been observed in the animal kingdom. RIA analysis confirmed that these plants contain significant amounts of this substance. Furthermore, reverse-phase HPLC analyses of plant extracts showed an elution characteristic of the peptide identical to that of human ghrelin. In general, fruit from both plants had higher levels of the peptide than the vegetative parts.

Characterization of a novel continuous supermacroporous monolithic cryogel embedded with nanoparticles for protein chromatography

A novel continuous supermacroporous monolithic cryogel embedded with nanometer-size particles was prepared by the radical cryogenic co-polymerization of acrylamide (AAm), N, N′-methylene-bis-acrylamide (MBAAm), allyl glycidyl ether (AGE) and the dispersed surfactant-stabilized Fe 3O 4 nanoparticles under the freezing-temperature variation condition in a glass column. This special separation matrix has interconnected supermacropores with pore size of 10–50 μm, which permit the free-passage of microbial cells or cell debris in the culture fluids and then is interest in downstream processes. The axial liquid dispersion coefficients of the new continuous supermacroporous monolithic bed at different liquid flow rates were obtained by measuring residence time distributions (RTDs) using tracer pulse-response method. The experimental results showed that the axial liquid dispersion within the bed was weak in a wide water flow rate of 0.5–15 cm/min. The axial dispersion coefficient was found to be increased exponentially with the increase of liquid flow rate. Chromatographic process of bovine serum albumin (BSA) in the cryogel monolithic bed was carried out to reveal the protein breakthrough and elution characteristics. Compared with other reported cryogel beds in literature, the protein adsorption capacity of the present cryogel bed was improved due to the embedded nano-sized solid adsorbents in the gel matrix. Microstructure morphology of the embedded nanoparticles in the cryogel and the gel matrix structure were also analyzed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in this paper.

Antibiotic-impregnated PMMA hip spacers: Current status

The infection rate after primary hip arthroplasty lies at 1–2%. In the past few years, a two-stage protocol with the implantation of an antibiotic-loaded spacer has become a popular procedure in the treatment of infected hip joint arthroplasties. In this review, we pay special attention to the elution characteristics of the spacers, their mechanical stability and the clinical response. We conclude that hip spacers are an effective method in the treatment of hip joint infections, with success rates of over 90%.

We-P11:260 Eluting characteristics of a platelet glycoprotein receptor antibody polymer-coated stent

We-P11:260 Eluting characteristics of a platelet glycoprotein receptor antibody polymer-coated stent

In Vivo and In Vitro Studies of Antibiotic Release from and Bacterial Growth Inhibition by Antibiotic-Impregnated Polymethylmethacrylate Hip Spacers

The antimicrobial properties and the elution characteristics of gentamicin-vancomycin-loaded hip spacers were studied in vivo and in vitro. Vancomycin elution was greater than gentamicin elution. The antibiotic concentrations in vivo were less than those in vitro. Not dependent on implantation duration, growth inhibition by spacers in vitro was observed for 2 weeks. The reason for protracted wound healing cannot be insufficient antibiotic release.

THE OTTO AUFRANC AWARD: Bone Augmentation around and within Porous Implants by Local Bisphosphonate Elution

The bisphosphonate zoledronic acid chemically and physically was bound to hydroxyapatite-coated porous tantalum implants. The zoledronic acid elution characteristics in saline were determined as a function of time and the in vivo effects of elution were quantified at 12 weeks in a canine ulnar implant model. Intramedullary implants surgically were implanted bilaterally into the ulnae of a control group of five dogs and a zoledronic acid-dosed (0.05 mg zoledronic acid) group of four dogs. Computerized image analysis of undecalcified histologic sections was used to quantify the amount of peri-implant bone within the intramedullary canal, the percentage of available pore space filled with new bone, and the number and size of the individual bone islands within the implant pores. The data were analyzed using a hierarchical analysis of variance with 95% confidence intervals. The peri-implant bone occupied a mean of 13.8% of the canal space in controls and 32.2% of the canal space in zoledronic acid-dosed dogs, a relative difference of 134% (2.34-fold) that was significant. The mean extent of bone ingrowth was 12.5% for the control implants and 19.8% for the zoledronic acid-dosed dogs, a relative difference of 58% that was statistically significant. Individual islands of new bone formation with the implant pores were similar in number in both implant groups but were 71% larger on average in the ZA-dosed group. We are the first authors to show that local elution of a bisphosphonate can cause substantial bone augmentation around and within porous orthopaedic implants. The concept represents a potential tool for restoration of bone stock and enhancement of implant fixation in primary and revision cementless joint arthroplasty surgeries in the face of compromised or deficient bone.

Development, implantation, in vivo elution, and retrieval of a biocompatible, sustained release subretinal drug delivery system

A biocompatible, sustained-release subretinal drug-delivery platform was developed to overcome the therapeutic accessibility limitations of current retinal disease treatments. The prototype implants were fabricated by coating nitinol, poly(methyl methacrylate) or chromic gut core filaments, with a drug-eluting polymer matrix. The polymer coatings are manufactured and coated by SurModics. The coating is a mixture of poly(butyl methacrylate) and poly(ethylene-co-vinyl acetate). The drug is either triamcinolone acetonide or sirolimus. The rods were successfully implanted into the subretinal space of 20/24 rabbits. Four rabbits were lost to early surgery from a dysfunctional infusion line and hemorrhage. No serious complications were observed during the 4-week follow-up period. Slight conjunctival redness was reported in all rabbits by 1-day follow-up, but the redness had subsided by the following week. Intraocular lens touch occurred in six rabbits during the implantations; of these, four had a lensectomy at the time of surgery, and the remaining two developed cataract. Corneal edema developed in three rabbits by 1-week follow-up, but subsided within 2 weeks. Initial observations of the implantation and elution characteristics revealed that the implants are well tolerated by the retinal tissue and that the implant can elute triamcinolone acetonide for a period of at least 4 weeks without eliciting an inflammatory response or complications. There were adverse clinical indications with the sirolimus-loaded implants at the delivered dose. Device retrieval required an uncomplicated surgical procedure, and revealed no associated or adherent tissue. Implant drug content analysis and opacity changes to the polymer matrix coating following retrieval demonstrated the sustained elution of the drug.