Heparin-mediated antibiotic delivery from an electrochemically-aligned collagen sheet

2021 ◽  
pp. 1-12
Author(s):  
Olivia T. Cheng ◽  
Andrew P. Stein ◽  
Eric Babajanian ◽  
Kathryn R. Hoppe ◽  
Shawn Li ◽  
...  
Keyword(s):  
High Performance ◽  
Inhibitory Concentration ◽  
Medical Implants ◽  
Implantable Medical Devices ◽  
Antibiotic Solution ◽  
Inhibition Zones ◽  
Antibiotic Release ◽  
Local Antibiotic ◽  
Antibiotic Delivery

BACKGROUND: Implantable medical devices and hardware are prolific in medicine, but hardware associated infections remain a major issue. OBJECTIVE: To develop and evaluate a novel, biologic antimicrobial coating for medical implants. METHODS: Electrochemically compacted collagen sheets with and without crosslinked heparin were synthesized per protocol developed by our group. Sheets were incubated in antibiotic solution (gentamicin or moxifloxacin) overnight, and in vitro activity was assessed with five-day diffusion assays against Pseudomonas aeruginosa. Antibiotic release overtime from gentamicin infused sheets was determined using in vitro elution and high performance liquid chromatography (HPLC). RESULTS: Collagen-heparin-antibiotic sheets demonstrated larger growth inhibition zones against P. aeruginosa compared to collagen-antibiotic alone sheets. This activity persisted for five days and was not impacted by rinsing sheets prior to evaluation. Rinsed collagen-antibiotic sheets did not show any inhibition zones. Elution of gentamicin from collagen-heparin-gentamicin sheets was slow and remained above the minimal inhibitory concentration for gentamicin sensitive organisms for 29 days. Conversely, collagen-gentamicin sheets eluted their antibiotic payload within 24 hours. Overall, heparin associated sheets demonstrated larger inhibition zones against P. aeruginosa and prolonged elution profile via HPLC. CONCLUSION: We developed a novel, local antibiotic delivery system that could be used to coat medical implants/hardware in the future and reduce post-operative infections.

scholarly journals Evaluation of a bone filler scaffold for local antibiotic delivery to prevent Staphylococcus aureus infection in a contaminated bone defect

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karen E. Beenken ◽  
Mara J. Campbell ◽  
Aura M. Ramirez ◽  
Karrar Alghazali ◽  
Christopher M. Walker ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Defect ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Bovine Bone ◽  
Bone Filler ◽  
Antibiotic Release ◽  
Local Antibiotic ◽  
Antibiotic Delivery

AbstractWe previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles. The current study was aimed at evaluating the use of this scaffold as a means of local antibiotic delivery to prevent infection in a bone defect contaminated with Staphylococcus aureus. We evaluated two scaffold formulations with the same component ratios but differing overall porosity and surface area. Studies with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity correlated with increased uptake and prolonged antibiotic release. We also demonstrate that vancomycin can be passively loaded into either formulation in sufficient concentration to prevent infection in a rabbit model of a contaminated segmental bone defect. Moreover, even in those few cases in which complete eradication was not achieved, the number of viable bacteria in the bone was significantly reduced by treatment and there was no radiographic evidence of osteomyelitis. Radiographs and microcomputed tomography (µCT) analysis from the in vivo studies also suggested that the addition of vancomycin did not have any significant effect on the scaffold itself. These results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery to prevent infection in contaminated bone defects.

scholarly journals Biological and physicochemical stability of ceftazidime and aminophylline on glucose parenteral solution

2012 ◽  
Vol 48 (4) ◽  
pp. 691-698
Author(s):  
Carolina Alves dos Santos ◽  
Laura Oliveira-Nascimento ◽  
Marcos Camargo Knirsch ◽  
Marco Antônio Stephano ◽  
Adalberto Pessoa Júnior ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Performance ◽  
Inhibitory Concentration ◽  
Serum Levels ◽  
High Loss ◽  
Physicochemical Stability ◽  
Physicochemical Evaluation ◽  
The Mean ◽  
The Stability

Ceftazidime is a broad spectrum antibiotic administered mainly by the parenteral route, and it is especially effective against Pseudomonas aeruginosa. The period of time in which serum levels exceed the Minimum Inhibitory Concentration (MIC) is an important pharmacodynamic parameter for its efficacy. One of the forms to extend this period is to administer the antibiotic by continuous infusion, after prior dilution in a Parenteral Solution (PS). The present work assessed the stability of ceftazidime in 5% glucose PS for 24 hours, combined or not with aminophylline, through High Performance Liquid Chromatography (HPLC). The physicochemical evaluation was accompanied by in vitro antimicrobial activity compared MIC test in the 24-hour period. Escherichia coli and Pseudomonas aeruginosa were the microorganisms chosen for the MIC comparison. The HPLC analysis confirmed ceftazidime and aminophylline individual stability on PS, while the MIC values were slightly higher than the mean described in the literature. When both drugs were associated in the same PS, the ceftazidime concentration by HPLC decreased 25% after 24 hours. Not only did the MIC values show high loss of antibiotic activity within the same period, but also altered MIC values immediately after the preparation, which was not detected by HPLC. Our results indicate that this drug combination is not compatible, even if used right away, and that PS might not be the best vehicle for ceftazidime, emphasizing the importance of the MIC evaluation for drug interactions.

A Study on Electrospun Nanofibrous Mats for Local Antibiotic Delivery

2013 ◽  
Vol 829 ◽  
pp. 510-514 ◽  
Author(s):  
Mahboubeh Maleki ◽  
Mohammad Amani-Tehran ◽  
Masoud Latifi ◽  
Sanjay Mathur
Keyword(s):  
Structural Characteristics ◽  
Electrospun Nanofibers ◽  
Electrospinning Process ◽  
Static System ◽  
Antibiotic Drug ◽  
Paper Fabrication ◽  
Antibiotic Release ◽  
Reduced Toxicity ◽  
Local Antibiotic ◽  
Antibiotic Delivery

The demand for novel antibiotic-loaded electrospun nanofibrous structures has increased extremely in the recent years and has engaged the interests of scientists and engineers into a blend configuration of antibiotic drug and biocompatible polymers due to their unique applications in future of better therapeutic effect, reduced toxicity and sustained local antibiotic release over a period of time. One method to produce these antibiotic-loaded networks is by electrospinning process. However, it is very important to know structural characteristics and morphology of nanofibers for controlling the performance of the yields. In this paper, fabrication of electrospun nanofibers suited for antibiotic delivery system is investigated based on tetracycline hydrochloride as the antibiotic drug and poly (lactic-co-glycolic acid) as the biodegradable polymeric matrix. Furthermore, the effect of material and process parameters on morphology and release behavior of produced nonwovens is investigated. The efficacy of the medicated scaffolds using a static system for bacterial growth on agar plates was also proved.

Local Antibiotic Delivery with Bovine Cancellous Chips

2010 ◽  
Vol 26 (4) ◽  
pp. 491-506 ◽  
Author(s):  
Christine S. Lewis ◽  
Jordan Katz ◽  
Maribel I. Baker ◽  
Peter R. Supronowicz ◽  
Elise Gill ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Secondary Surgery ◽  
Primary Osteoblast ◽  
Systemic Antibiotic Therapy ◽  
Bone Void Filler ◽  
Orthopedic Applications ◽  
Local Antibiotic ◽  
Bone Void ◽  
Antibiotic Delivery

Infected bone defects and osteomyelitis are encountered frequently in trauma cases. Currently, the standard of care for osteomyelitis cases is prolonged systemic antibiotic therapy and implantation of antibiotic carrier beads. However, this method requires a secondary surgery to remove the beads after the infection has cleared. In the present study a common bone void filler was investigated for its ability to be infused with an antibiotic. This study demonstrates that the xenograft material tested can be loaded with gentamicin and release clinically relevant levels of the drug for at least 14 days in vitro allowing for the inhibition of bacterial growth on the graft. This study also demonstrates that the levels of gentamicin released did not have an adverse effect on primary osteoblast cell proliferation or ability to generate alkaline phosphatase. This bone void filler may represent a viable alternative to current methods of local antibiotic delivery in orthopedic applications.

scholarly journals HPLC analysis, antimicrobial and antioxidant activities of Daphne cneorum L.

2012 ◽  
Vol 66 (5) ◽  
pp. 709-716 ◽  
Author(s):  
Nedeljko Manojlovic ◽  
Pavle Maskovic ◽  
Perica Vasiljevic ◽  
Ratomir Jelic ◽  
Marina Juskovic ◽  
...  
Keyword(s):  
High Performance ◽  
Antimicrobial Agents ◽  
Inhibitory Concentration ◽  
Total Phenolics ◽  
Antioxidant Activities ◽  
High Performance Liquid Chromatographic ◽  
Hplc Method ◽  
Potential Source ◽  
Liquid Chromatographic

The present study describes in vitro antimicrobial and antioxidant activities of the methanol extracts which were obtained from the leaves and twigs of the plant Daphne cneorum L. The antimicrobial activity of these extracts was tested against human pathogenic microorganisms using a minimum inhibitory concentration (MIC) values. Total phenolics and flavonoids, as well as the antioxidant activity of the extracts were determined. The two tested extracts showed good antimicrobial and antioxidant activities. The results of a high performance liquid chromatographic (HPLC) method showed that 7,8-dihydroxycoumarin is one of the most abundant secondary metabolite in the tested extracts. The results of this study clearly indicated that the extracts of D. cneorum could be used as a potential source of natural antioxidant and antimicrobial agents.

scholarly journals Polyphenolic Profile and Varied Bioactivities of Processed Taiwanese Grown Broccoli: A Comparative Study of Edible and Non-Edible Parts

2020 ◽  
Vol 13 (5) ◽  
pp. 82 ◽  
Author(s):  
Thanh Ninh Le ◽  
Napat Sakulsataporn ◽  
Chiu-Hsia Chiu ◽  
Pao-Chuan Hsieh
Keyword(s):  
High Performance ◽  
Inhibitory Concentration ◽  
Antioxidant Activities ◽  
Antibacterial Properties ◽  
Pharmaceutical Products ◽  
Health Promoting ◽  
Weak Activity ◽  
Promising Source ◽  
Edible Parts

Broccoli contains a substantial amount of bioactive compounds such as glucosinolates, phenolics, and essential nutrients, which are positively linked to health-promoting effects. This work aimed to evaluate whether both edible and non-edible parts of broccoli could be effective by examining in vitro antioxidant, cytotoxic, apoptotic, and antibacterial properties of its floret, leaf, and seed extracts (FE, LE, and SE, correspondingly). High-performance liquid chromatography (HPLC) and various assays exhibited strong antioxidant activities of all samples. LE obtained the highest capacity, correlated to its polyphenolic contents. SE exerted significant cytotoxicity against A549, Caco-2, and HepG2 cancer cell lines at low inhibitory concentration (IC)50 values (0.134, 0.209, and 0.238 mg/mL, respectively), as tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry confirmed apoptosis induction of extracts in Caco-2 cells by revealing an increased subG1 population and a decreased mitochondrial membrane potential. The considerable antibacterial efficacy was observed in either LE and SE against Bacillus subtilis and Salmonella typhimurium (0.39–0.78 mg/mL) using well-agar diffusion and minimum inhibitory concentration (MIC) techniques, along with the weak activity against Staphylococcus aureus and Escherichia coli (1.56–3.13 mg/mL). The findings suggest that broccoli and its byproducts might serve as a promising source for further development of food or pharmaceutical products.

scholarly journals Development and Evaluation of an Injectable Chitosan/β-Glycerophosphate Paste as a Local Antibiotic Delivery System for Trauma Care

2018 ◽  
Vol 9 (4) ◽  
pp. 56 ◽  
Author(s):  
Logan Boles ◽  
Christopher Alexander ◽  
Leslie Pace ◽  
Warren Haggard ◽  
Joel Bumgardner ◽  
...  
Keyword(s):  
Delivery System ◽  
Infection Prevention ◽  
Wound Site ◽  
Ejection Force ◽  
Relative Viability ◽  
Further Development ◽  
Local Antibiotic ◽  
Antibiotic Delivery

Complex open musculoskeletal wounds are a leading cause of morbidity worldwide, partially due to a high risk of bacterial contamination. Local delivery systems may be used as adjunctive therapies to prevent infection, but they may be nondegradable, possess inadequate wound coverage, or migrate from the wound site. To address this issue, a thermo-responsive, injectable chitosan paste was fabricated by incorporating beta-glycerophosphate. The efficacy of thermo-paste as an adjunctive infection prevention tool was evaluated in terms of cytocompatibility, degradation, antibacterial, injectability, and inflammation properties. In vitro studies demonstrated thermo-paste may be loaded with amikacin and vancomycin and release inhibitory levels for at least 3 days. Further, approximately 60% of thermo-paste was enzymatically degraded within 7 days in vitro. The viability of cells exposed to thermo-paste exceeded ISO 10993-5 standards with approximately 73% relative viability of a control chitosan sponge. The ejection force of thermo-paste, approximately 20 N, was lower than previously studied paste formulations and within relevant clinical ejection force ranges. An in vivo murine biocompatibility study demonstrated that thermo-paste induced minimal inflammation after implantation for 7 days, similar to previously developed chitosan pastes. Results from these preliminary preclinical studies indicate that thermo-paste shows promise for further development as an antibiotic delivery system for infection prevention.

scholarly journals Identification of Digestive Enzyme Inhibitors from Ludwigia octovalvis (Jacq.) P.H.Raven

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Dulce Morales ◽  
Guillermo Ramirez ◽  
Armando Herrera-Arellano ◽  
Jaime Tortoriello ◽  
Miguel Zavala ◽  
...  
Keyword(s):  
High Performance ◽  
Inhibitory Concentration ◽  
Enzyme Inhibitors ◽  
Competitive Inhibition ◽  
Digestive Enzyme ◽  
Chemical Compounds ◽  
Ethyl Acetate Fraction ◽  
Hydroalcoholic Extract ◽  
Glucosidase Inhibitors

Current antiobesity and antidiabetic tools have been insufficient to curb these diseases and frequently cause side effects; therefore, new pancreatic lipase and α–glucosidase inhibitors could be excellent aids for the prevention and treatment of these diseases. The aim of this study was to identify, quantify, and characterize the chemical compounds with the highest degree of inhibitory activity of these enzymes, contained in a Ludwigia octovalvis hydroalcoholic extract. Chemical purification was performed by liquid–liquid separation and column chromatography. Inhibitory activities were measured in vitro, employing acarbose, orlistat, and a Camellia sinensis hydroalcoholic extract as references. For structural elucidation, Nuclear Magnetic Resonance was carried out, and High Performance Liquid Chromatography was used to quantify the compounds. For α–glucosidases, L. octovalvis hydroalcoholic extract and its ethyl acetate fraction showed half–maximal Inhibitory Concentration (IC50) values of 700 and 250 μg/mL, for lipase, 480 and 718 μg/mL, while C. sinensis showed 260 and 587 μg/mL. The most active compounds were identified as ethyl gallate (1, IC50 832 μM) and gallic acid (2, IC50 969 μM); both displayed competitive inhibition of α–glucosidases and isoorientin (3, IC50 201 μM), which displayed uncompetitive inhibition of lipase. These data could be useful in the development of a novel phytopharmaceutical drug.

scholarly journals Antibiotic Elution from Hip and Knee Acrylic Bone Cement Spacers: A Systematic Review

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Konstantinos Anagnostakos ◽  
Christof Meyer
Keyword(s):  
Inhibitory Concentration ◽  
Clinical Success ◽  
Acrylic Bone Cement ◽  
Future Studies ◽  
Search Terms ◽  
Custom Made ◽  
Pubmed Search ◽  
Antibiotic Release ◽  
Local Antibiotic ◽  
Antibiotic Combination

Knowledge about the elution from antibiotic-loaded cement spacers is an indispensable premise for guarantee of clinical success. A systematic literature search was performed through PubMed. Search terms were “antibiotic elution” and “antibiotic release” in combination with “spacer,” “hip spacer,” and “knee spacer,” respectively. A total of 11 studies could be identified. Seven studies reported on the release of antibiotics after spacer implantation, three studies at spacer removal, and one study on both time points. Seven studies reported on hip spacers, one study on knee spacers, and three studies on both. In eight studies, custom-made spacers have been implanted and in three prefabricated ones. In the majority of the studies, the cement has been loaded with an antibiotic combination, mostly consisting of aminoglycoside (either gentamicin or tobramycin) and vancomycin. Measured concentrations exceeded the minimal inhibitory concentration of the particular pathogen organisms in each case. However, large discrepancies were observed with regard to the height of the antibiotic concentration depending on the antibiotic combination and the antibiotic ratio used. Current literature data indicate a sufficient elution of antibiotics after spacer implantation and at spacer removal, respectively. Future studies are required to optimize the local antibiotic therapy at the site of spacer implantation.

Drug Delivery Assessment of a Novel Triple Antibiotic-Eluting Injectable Platelet-Rich Fibrin Scaffold: An in-vitro Study.

2020 ◽  
Vol 21 ◽  
Author(s):  
Azade Rafiee ◽  
Mahtab Memarpour ◽  
Sara Taghvamanesh ◽  
Forough Karami ◽  
Somayeh Karami ◽  
...  
Keyword(s):  
High Performance ◽  
In Vitro Study ◽  
Vitro Study ◽  
Burst Release ◽  
Platelet Rich Fibrin ◽  
Fibrin Scaffold ◽  
Antibiotic Release ◽  
Simultaneous Identification

Background: Intracanal disinfection is a critical, yet challenging goal for the long-term success in regenerative-based treatments. This in-vitro study aimed to assess the release profile of triple antibiotic-eluting injectable platelet-rich fibrin (I-PRF) constructs in 28 days. Methods: I-PRF scaffolds containing triple antibiotic mixture [metronidazole (MET), ciprofloxacin (CIP), and minocycline (MINO)] by immersion (group one), I-PRF scaffolds containing triple antibiotic mixture by integration (group two), and antibiotic-free I-PRF scaffolds (group three) were fabricated. The antibiotic release from the scaffolds was measured using a high performance liquid chromatography (HPLC) (the mobile phase of 0.1% formic acid and methanol (35:65 v/v), a C18 analytical column (150 × 4.6 mm, 5 μm) at a flow rate of 0.7 mL/min, at 25ºC) at days 1, 3, 7, 14, 21, and 28. Results: Retention times for MINO, CIP, and MET were achieved as 2.3, 2.6, and 3.1 min, respectively. The maximum UV absorbances for CIP, MET, and MINO were at 268 nm, 278 nm, and 350 nm, respectively. The results of the first group showed burst release within the first 24 hours followed by sustained maintenance of all three antibiotics up to 14 days. MINO and MET were still detectable in the third week. The second group could not sustainably release of the antibiotics. Conclusions: The developed method for the simultaneous identification, and quantification of each antibiotic in I-PRF was sensitive and quick. Overall, group one could take up the antibiotics in adequate quantities and then subsequently release them over the study period.

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