scholarly journals Digital drug delivery: on–off ultrasound controlled antibiotic release from coated matrices with negligible background leaching

2014 ◽  
Vol 2 (6) ◽  
pp. 893-902 ◽  
Author(s):  
Misty L. Noble ◽  
Pierre D. Mourad ◽  
Buddy D. Ratner

An ultrasound-responsive pHEMA-based system is created for local antibiotic delivery to treat biofilm-related or device-centered infections.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karen E. Beenken ◽  
Mara J. Campbell ◽  
Aura M. Ramirez ◽  
Karrar Alghazali ◽  
Christopher M. Walker ◽  
...  

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.


2021 ◽  
pp. 1-12
Author(s):  
Olivia T. Cheng ◽  
Andrew P. Stein ◽  
Eric Babajanian ◽  
Kathryn R. Hoppe ◽  
Shawn Li ◽  
...  

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.


2013 ◽  
Vol 829 ◽  
pp. 510-514 ◽  
Author(s):  
Mahboubeh Maleki ◽  
Mohammad Amani-Tehran ◽  
Masoud Latifi ◽  
Sanjay Mathur

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.


1987 ◽  
Vol 21 (4) ◽  
pp. 322-329 ◽  
Author(s):  
Susan A. Stout ◽  
Hartmut Derendorf

Local administration of antibiotics for the treatment of respiratory infections has the potential advantage of reduced systemic toxicity and increased drug concentration at the site of infection. This article reviews the basic principles of pulmonary drug delivery using aerosols and the clinical efficacy of local antibiotic therapy of respiratory infections. Clinical studies have been conducted with locally administered aminoglycosides, penicillins, cephalosporins, and polypeptides. The results of these investigations and the pharmacokinetic aspects of pulmonary antibiotic delivery are summarized.


2018 ◽  
Vol 100-B (11) ◽  
pp. 1409-1415 ◽  
Author(s):  
B. A. Marson ◽  
S. R. Deshmukh ◽  
D. J. C. Grindlay ◽  
B. J. Ollivere ◽  
B. E. Scammell

Aims Local antibiotics are used in the surgical management of foot infection in diabetic patients. This systematic review analyzes the available evidence of the use of local antibiotic delivery systems as an adjunct to surgery. Materials and Methods Databases were searched to identify eligible studies and 13 were identified for inclusion. Results Overall, the quality of the studies was poor. A single trial suggested that wound healing is quicker when a gentamicin-impregnated collagen sponge was implanted at time of surgery, with no difference in length of stay or rate of amputation. Results from studies with high risk of bias indicated no change in wound healing when a gentamicin-impregnated sponge was implanted during transmetatarsal amputation, but a reduction in the incidence of wound breakdown (8% vs 25%, not statistically significant) was identified. A significant cost reduction was identified when using an antimicrobial gel to deliver antibiotics and anti-biofilm agents (quorum-sensing inhibitors) compared with routine dressings and systemic antibiotics. Analyses of case series identified 485 patients who were treated using local antibiotic delivery devices. The rates of wound healing, re-operation, and mortality were comparable to those that have been previously reported for the routine management of these infections. Conclusion There is a lack of good-quality evidence to support the use of local antibiotic delivery devices in the treatment of foot infections in patients with diabetes. Cite this article: Bone Joint J 2018;100-B:1409–15.


Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 517 ◽  
Author(s):  
Leslie R. Pace ◽  
Zoe L. Harrison ◽  
Madison N. Brown ◽  
Warren O. Haggard ◽  
J. Amber Jennings

Mannitol, a polyalcohol bacterial metabolite, has been shown to activate dormant persister cells within bacterial biofilm. This study sought to evaluate an injectable blend of mannitol, chitosan, and polyethylene glycol for delivery of antibiotics and mannitol for eradication of Staphylococcal biofilm. Mannitol blends were injectable and had decreased dissociation and degradation in the enzyme lysozyme compared to blends without mannitol. Vancomycin and amikacin eluted in a burst response, with active concentrations extended to seven days compared to five days for blends without mannitol. Mannitol eluted from the paste in a burst the first day and continued through Day 4. Eluates from the mannitol pastes with and without antibiotics decreased viability of established S. aureus biofilm by up to 95.5% compared to blends without mannitol, which only decreased biofilm when loaded with antibiotics. Cytocompatibility tests indicated no adverse effects on viability of fibroblasts. In vivo evaluation of inflammatory response revealed mannitol blends scored within the 2–4 range at Week 1 (2.6 ± 1.1) and at Week 4 (3.0 ± 0.8), indicative of moderate inflammation and comparable to non-mannitol pastes (p = 0.065). Clinically, this paste could be loaded with clinician-selected antibiotics and used as an adjunctive therapy for musculoskeletal infection prevention and treatment.


2019 ◽  
Vol 2019 (11) ◽  
Author(s):  
Anoop Anugraha ◽  
Luke D Hughes ◽  
Anand Pillai

Abstract Deformity correction in the setting of osteomyelitis is a challenge for any orthopaedic surgeon. Principles of management are well described and include staged debridement, stable fixation and a combination of local and systemic antibiotic therapy. An antibiotic-coated nail (ACN) can prove a useful tool—stabilizing bone, whilst allowing for local antibiotic elution. Typically, the surgeon will prepare these implants in the operating room using materials that are routinely at hand. Most frequently, this will involve the use of antibiotic-loaded poly-methyl methacrylate (PMMA). This method of ACN fabrication has several disadvantages. PMMA is non-degradable and can be difficult to remove surgically. There are limitations with regard to antibiotic suitability, antibiotic release as well as toxicity effects. In this case report, we present a novel technique for the preparation of ACNs for use in hindfoot surgery, using a calcium sulphate/hydroxyapatite-based bio-composite—Cerament-V.


2017 ◽  
Vol 8 (2) ◽  
pp. 130 ◽  
Author(s):  
Cheyenne S Rhodes ◽  
Christopher M Alexander ◽  
Joel M Berretta ◽  
Harry S Courtney ◽  
Karen E Beenken ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-31
Author(s):  
Antonio Vassallo ◽  
Maria Francesca Silletti ◽  
Immacolata Faraone ◽  
Luigi Milella

Today’s human society, product of decades of progress in all fields of knowledge, would have been unimaginable without the discovery of antibiotics and more generally of antimicrobials. However, from the beginning, the scientific community was aware that microorganisms through various strategies were able to hinder and render vain antibiotic action. Common examples are the phenomena of persistence, tolerance, and resistance, up to the creation of the feared bacterial biofilms. Antibiotics are a precious but equally labile resource that must be preserved but at the same time reinforced to safeguard their effectiveness. Nanoparticulate systems such as nanobactericides, with their inherent antibacterial activity, and nanocarriers, which operate as drug delivery systems for conventional antibiotics, are innovative therapies made available by nanotechnology. Inorganic nanoparticles are effective both as nanobactericides (AgNPs, ZnONPs, and TiO2NPs) and as nanocarriers (AgNPs, AuNPs, ZnONPs, and TiO2NPs) against sensitive and multi-drug-resistant bacterial strains. Liposomes are among the most studied and flexible antibiotic delivery platforms: conventional liposomes allow passive targeting at the mononuclear phagocytic system (MPS); “stealth” liposomes prevent macrophage uptake so as to eradicate infections in tissues and organs outside MPS; thanks to their positive charge, cationic liposomes interact preferentially with bacterial and biofilm surfaces, acting as innate antibacterials as well as drug delivery systems (DDS); fusogenic liposomes have fluid bilayers that promote fusion with microbial membranes; and finally, ligand-targeted liposomes provide active targeting at infection sites. Dendrimers are among the most recent and attractive nanoparticulate systems, thanks to their multibranched nanoarchitecture, which equipped them with multiple active sites for loading antibiotics and also interacting with bacteria. Finally, nanoantibiotics represent a new hopeful generation of antibiotic candidates capable of increasing or even restoring the clinical efficacy of “old” antibiotics rendered useless by the resistance phenomena.


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