Sustained Release Of Antibiotics Research Articles

Development of antibacterial and high light transmittance bulk materials: Incorporation and sustained release of hydrophobic or hydrophilic antibiotics

Infection associated with medical devices is one of the most frequent complications of modern medical biomaterials. Bacteria have a strong ability to attach on solid surfaces, forming colonies and subsequently biofilms. In this work, a novel antibacterial bulk material was prepared through combining poly(dimethyl siloxane) (PDMS) with either hydrophobic or hydrophilic antibiotics (0.1–0.2wt%). Scanning electron microscopy, water contact angle and UV–vis spectrophotometer were used to measure the changes of surface topography, wettability and optical transmission. For both gentamicin sulfate (GS) and triclosan (TCA), the optical transmission of the PDMS-GS and PDMS-TCA blend films was higher than 90%. Drug release studies showed initial rapid release and later sustained release of GS or TCA under aqueous physiological conditions. The blend films demonstrated excellent bactericidal and sufficient biofilm inhibition functions against Gram-positive bacteria (Staphylococcus aureus, S. aureus) measured by LIVE/DEAD bacterial viability kit staining method. Kirby-Bauer method showed that there was obvious zone of inhibition (7.5–12.5mm). Cytocompatibility assessment against human lens epithelial cells (HLECs) revealed that the PDMS-GS blend films had good cytocompatibility. However, the PDMS-TCA blend films showed certain cytotoxicity against HLECs. The PDMS-0.2wt% GS blend films were compared to native PDMS in the rabbit subcutaneous S. aureus infection model. The blend films yielded a significantly lower degree of infection than native PDMS at day 7. The achievement of the PDMS-drug bulk materials with high light transmittance, excellent bactericidal function and good cytocompatibility can potentially be widely used as bio-optical materials.

Silk fibroin nanoparticles support in vitro sustained antibiotic release and osteogenesis on titanium surface

Increasing amounts of metal-based implants are used for orthopedic or dental surgeries throughout the world. Still several implant-related problems such as inflammation, loosening and bacterial infection are prevalent. These problems stem from the immediate microbial contamination and failure of initial osteoblast adhesion. Additionally, bacterial infections can cause serious and life-threatening conditions such as osteomyelitis. Here, antibiotic (gentamicin)-loaded silk protein fibroin (non-mulberry silkworm, Antheraea mylitta) nanoparticles are fabricated and deposited over the titanium surface to achieve sustained drug release in vitro and to alter the surface nano-roughness. Based on the altered surface topography, chemistry and antibacterial activity, we conclude that the nanoparticle-deposited surfaces are superior for osteoblast adhesion, proliferation and differentiation in comparison to bare Ti. This method can be utilized as a cost-effective approach in implant modification. From the Clinical EditorTitanium-based implants are commonly used in the field of orthopedics or dentistry. Surface modification of an implant is vital to ensure osseointegration. In this article, the author investigated the use of silk protein fibroins for metal surface modification and also for drug delivery against bacteria. The encouraging data should provide a new method in terms of nanotechnology in the respective clinical fields.

Prospective study of infected non-union of long bones treated by Antibiotic impregnated intramedullary nailing

Background: In a era of high velocity injuries, compound fractures are very common in orthopaedic practice n despite of preventive measures taken pre operatively and post operatively, infected non unions still common and they pose real challenge to the treating surgeon and makes the patient debilitating. In infected non-union case, the preference has to be given to eradication of the infection before aiming to achieve fracture union. Many methods of treatment have been described in the past including ilizarov fixator and Antibiotic cement impregnated intramedullary nailing(ACIIMN). Sustained and gradual release of heat stable antibiotics which are mixed with the bone cement at a high concentration and coating it on Intramedullary nail(ACIIMN) has gained popularity among the techniques used to treat infected non unions. Our study is aimed at summarizing our experience with the use of antibiotic cement-impregnated intramedullary nail (ACIIMN) for control of infection in cases of infected non-union. This is a report of series of 27 infected non union cases, both femur and tibia which were treated by Antibiotic cement impregnated intramedullary nailing(ACIIMN) in our institute. Aims and objectives: To evaluate the outcome of treatment of infected nonunions of long bones treated by Antibiotic cement impregnated intramedullary nailing(ACIIMN). Materials and Methods: Our’s is prospective study involving 27 cases of infected nonunions of long bones treated by Antibiotic cement impregnated intramedullary nailing(ACIIMN) at our institute from 2012- 2015. The outcome of procedure was evaluated with regards to infection control, deformity, bony union and limb length discrepancy etc. Results: Infection was eradicated in 23 cases with ACIIN and the fractures united. In 4 cases, though the infection was controlled with ACIIN, they required subsequent procedures like exchange nailing with bone grafting to achieve bony union. Conclusion: Antibiotic cement impregnated nailing is a very simple yet economical and very effective procedure than the other methods in treatment of infected non-unions of long bones. Keywords: long bones, Infected non-union, antibiotic cement impregnated intramedullary nail

Enzyme-Responsive Polymeric Vesicles for Bacterial-Strain-Selective Delivery of Antimicrobial Agents.

Antimicrobial resistance poses serious public health concerns and antibiotic misuse/abuse further complicates the situation; thus, it remains a considerable challenge to optimize/improve the usage of currently available drugs. We report a general strategy to construct a bacterial strain-selective delivery system for antibiotics based on responsive polymeric vesicles. In response to enzymes including penicillin G amidase (PGA) and β-lactamase (Bla), which are closely associated with drug-resistant bacterial strains, antibiotic-loaded polymeric vesicles undergo self-immolative structural rearrangement and morphological transitions, leading to sustained release of antibiotics. Enhanced stability, reduced side effects, and bacterial strain-selective drug release were achieved. Considering that Bla is the main cause of bacterial resistance to β-lactam antibiotic drugs, as a further validation, we demonstrate methicillin-resistant S. aureus (MRSA)-triggered release of antibiotics from Bla-degradable polymeric vesicles, in vitro inhibition of MRSA growth, and enhanced wound healing in an in vivo murine model.

Enzyme‐Responsive Polymeric Vesicles for Bacterial‐Strain‐Selective Delivery of Antimicrobial Agents

AbstractAntimicrobial resistance poses serious public health concerns and antibiotic misuse/abuse further complicates the situation; thus, it remains a considerable challenge to optimize/improve the usage of currently available drugs. We report a general strategy to construct a bacterial strain‐selective delivery system for antibiotics based on responsive polymeric vesicles. In response to enzymes including penicillin G amidase (PGA) and β‐lactamase (Bla), which are closely associated with drug‐resistant bacterial strains, antibiotic‐loaded polymeric vesicles undergo self‐immolative structural rearrangement and morphological transitions, leading to sustained release of antibiotics. Enhanced stability, reduced side effects, and bacterial strain‐selective drug release were achieved. Considering that Bla is the main cause of bacterial resistance to β‐lactam antibiotic drugs, as a further validation, we demonstrate methicillin‐resistant S. aureus (MRSA)‐triggered release of antibiotics from Bla‐degradable polymeric vesicles, in vitro inhibition of MRSA growth, and enhanced wound healing in an in vivo murine model.

A resorbable antibiotic eluting bone void filler for periprosthetic joint infection prevention.

Periprosthetic joint infection (PJI) following total knee arthroplasty is a globally increasing procedural complication. These infections are difficult to treat and typically require revision surgery. Antibiotic-loaded bone cement is frequently utilized to deliver antibiotics to the site of infection; however, bone cement is a nondegrading foreign body and known to leach its antibiotic load, after an initial burst release, at subtherapeutic concentrations for months. This work characterized a resorbable, antibiotic-eluting bone void filler designed to restore bone volume and prevent PJI. Three device formulations were fabricated, consisting of different combinations of synthetic inorganic bone graft material, degradable polymer matrices, salt porogens, and antibiotic tobramycin. These formulations were examined to determine the antibiotic's elution kinetics and bactericidal potential, the device's degradation in vitro, as well as osteoconductivity and device resorption in vivo using a pilot rabbit bone implant model. Kirby-Bauer antibiotic susceptibility tests assessed bactericidal activity. Liquid chromatography with tandem mass spectrometry measured antibiotic elution kinetics, and scanning electron microscopy was used to qualitatively assess degradation. Results indicated sustained antibiotic release from all three formulations above the Staphylococcus aureus minimum inhibitory concentration for a period of 5 to 8 weeks. Extensive degradation was observed with the Group 3 formulation after 90 days in phosphate-buffered saline, with a lesser degree of degradation observed in the other two formulations. Results from the pilot rabbit study showed the Group 3 device to be biocompatible, with minimal inflammatory response and no fibrous encapsulation in bone. The device was also highly osteoconductive-exhibiting an accelerated mineral apposition rate. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1632-1642, 2016.

Bacteria responsive antibacterial surfaces for indwelling device infections

Indwelling device infections now represent life-threatening circumstances as a result of the biofilms' tolerance to antibiotic treatments. Current antibiotic impregnation approaches through sustained antibiotic release have some unsolved problems which include short life-span, narrowed antibacterial spectrum, ineffectiveness towards resistant mutants, and the potential to hasten the antibiotic resistance process. In this study, bacteria responsive anti-biofilm surfaces were developed using bioactive peptides with proved activity to antibiotic resistant bacteria and biofilms. Resulting surfaces were stable under physiological conditions and in the presence of high concentrations of salts (0.5M NaCl) and biomacromolcules (1.0% DNA and 2.0% alginate), and thus showed good biocompatibility to various tissue cells. However, lytic peptide immobilized surfaces could sense bacteria adhesion and kill attached bacteria effectively and specifically, so biofilms were unable to develop on the lytic peptide immobilized surfaces. Bacteria responsive catheters remained biofilm free for up to a week. Therefore, the bacteria responsive antibacterial surfaces developed in this study represent new opportunities for indwelling device infections.

Sustained release of antibiotic complexed by multivalent ion: In vitro and in vivo study for the treatment of peritonitis

The main aims of this study are (i) the development of an antibiotic complexed with multivalent ion, which can allow sustained release of the antibiotic without any additional matrix or difficult process and (ii) the feasibility study of the ion-complexed antibiotic as a therapeutic technique for peritonitis treatment. An ion-complexed antibiotic is prepared by simple mixing of two aqueous solutions containing an ionized (water-soluble) drug (tetracycline) and a multivalent counter ionic compound. The ion-complexed antibiotic shows a continuous release of the antibiotic up to 21 days, and thus prolonged anti-bacterial effect by gradual ionic exchange between the multivalent ions in the complex and same-charged monovalent ions in surrounding medium. From the in vivo animal study using a cecum perforated peritonitis mouse model, the ion-complexed antibiotic group shows sufficient anti-bacterial effect and thus effectively treat the peritonitis because of the extermination of the contaminated enteric bacteria in the peritoneum during wound healing of injury cecum (by the sustained release of antibiotic from the ion complex). These results suggest that the ion-complexed antibiotic system may be promising for the effective treatment of the peritonitis caused by frequent gastrointestinal defect in clinical fields.

Drug delivery property, antibacterial performance and cytocompatibility of gentamicin loaded poly(lactic-co-glycolic acid) coating on porous magnesium scaffold

Implant associated infection remains a difficult medical problem in orthopaedic surgery. Here, we report on the fabrication of gentamicin loaded poly(lactic-co-glycolic acid) (PLGA) coating on porous magnesium scaffold (Gent-PLGA-Mg) for use as a type of controlled antibiotic delivery system bone scaffolds to achieve the sustained release of antibiotics in the local sites of bone defects. The drug loaded PLGA coating of Mg scaffold enable higher drug loading efficiency (28–33%) than non-coating gentamicin loaded Mg scaffold (Gent-Mg) (2–3%). The Gent-PLGA-Mg exhibited sustained drug release for more than 14 days, and this controlled release of gentamicin significantly inhibited bacterial adhesion and prevented biofilm formation by Staphylococcus aureus (ATCC25923) and Staphylococcus epidermidis (ATCC35984). Biocompatibility tests with human bone marrow stromal cells indicated that PLGA-Mg had better biocompatibility than Mg. Therefore, Gent-PLGA-Mg is potential to be used as a controlled drug delivery system bone scaffolds to prevent and/or treat orthopaedic peri-implant infections.

Thrombin and Topical Local Anesthetic for Postoperative Pain Management

Local anesthetic is often used for perioperative pain control. Thrombin serves as a carrying medium for sustained release of antibiotics, chemotherapy, and growth factors. We tested the hypothesis that local anesthetic pain relief can be prolonged with the adjunct use of thrombin. A prospective single-blinded clinical study was performed. Patients undergoing elective hand surgery inclusive of carpal tunnel release, excision of ganglion cyst, trigger finger release, and excision of mucous cyst under local block were enlisted. Before closure, patients received 1 of the following combinations: (1) control with oral analgesics, (2) 5 mL of 2% xylocaine, (3) 5 mL of 0.5% bupivacaine, (4) 2.5 mL of 2% xylocaine with 2.5 mL of 0.5% bupivacaine (XB), (5) thrombin with 5 mL of 2% xylocaine (XT), (6) thrombin with 5 mL of 0.5% bupivacaine (BT), and (7) thrombin with 2.5 mL of 2% xylocaine and 2.5 mL of 0.5% bupivacaine (XBT). There were 7 patients in each group, and patient demographics were similar between groups. Outcome measures included postanesthesia care unit (PACU) time, pain level, and number of pain pills required. Compared with oral analgesics alone, mean (SD) postoperative pain levels were reduced by 33.3% (8.9%) by xylocaine, 69.1% (8.7%) by bupivacaine, and 45.7% (9.4%) by XB. When thrombin was added, pain levels were further reduced by 69.9% by XT (P < 0.001), 23.1% by BT (P = 0.071), and 50.5% by XBT (P < 0.001) compared with their nonthrombin counterparts. In addition, PACU time was decreased by 34.8% by XT (P = 0.003) and 19.7% by XBT (P = 0.013) compared with xylocaine and XB, respectively. However, there was no difference in total pain pills needed between xylocaine, bupivacaine, and XB when administered with and without thrombin. The addition of topical thrombin to local anesthetic at the end of elective hand surgery provides for sustained postoperative pain control. Patients in this study who received thrombin and local anesthetic before wound closure had lower pain levels and were discharged from the PACU sooner than those who received local anesthetic alone. Therapeutic level 2.

Sustained release of antibiotics from uniform poly (ε-caprolactone) microspheres prepared by a simple fluidic device with a tapered glass capillary

Uniform poly(ε-caprolactone) microspheres containing a variety of water-soluble antibiotics, such as tobramycin, vancomycin, and gentamicin, were prepared by a simple fluidic device with a pristine or tapered glass capillary. Each type of antibiotic was dispersed in an organic solvent by ball-milling prior to microsphere preparation. The poly(ε-caprolactone) organic solution containing the powder of each antibiotic was introduced as the discontinuous phase into the fluidic device, where an aqueous phase containing surfactant served as the continuous phase. The poly(ε-caprolactone) microspheres were obtained after solvent evaporation. A tapered glass capillary was tested to produce poly(ε-caprolactone) microspheres, leading to the size reduction of the microspheres from 47.46 ± 0.72 to 25.49 ± 1.05 µm without destroying size uniformity. This size range should be suitable for parenteral injection into the human body. The release analysis revealed that gentamicin and vancomycin were released from the poly(ε-caprolactone) microspheres up to approximately 2 months in a more sustained manner than tobramycin, which is due to the solubility difference in the antibiotics in water. The antimicrobial activities of each type of antibiotic released from the poly(ε-caprolactone) microspheres were evaluated using Staphylococcus aureus and Escherichia coli.

Fibrin sealant as a carrier for sustained delivery of antibiotics

Objective: To evaluate the activity and sustained release of antibiotics from fibrin sealant against common strains of ocular bacteria. Methods: Vancomycin, ceftazidime, moxifloxacin and lomefloxacin were incorporated into fibrin sealant in the shape of discs. Each antibiotic disc and control fibrin disc without drug was tested in vitro against standard bacterial strains of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae and Pseudomonas aeroginosa. After 24 hours of incubation at 37 °C, the discs were transferred to new plates of bacteria and triplicated for each antibiotic. Results: All antibiotic discs demonstrated detectable activity after 24 hours. Vancomycin had the longest duration of activity (4 days) on the S. pneumonia grown plate. The moxifloxacin discs showed a prolonged inhibition of S. aureus and S. pneumonia for 3 days and inhibited the other strains for 2 days. Conclusion: Fibrin sealants provided prolonged drug delivery, which indicates that antibiotic-loaded fibrin clots could be useful for early ocular postoperative care and treatment.

PREPARATION AND CHARACTERIZATIONS OF ANTIBIOTIC IMPREGNATED MICROPOROUS NANO-HYDROXYAPATITE FOR OSTEOMYELITIS TREATMENT

In this study, preparation and characterization of antibiotic-impregnated microporous nano-hydroxyapatite (HA) aiming to function as both antibiotic carrier and bone graft for osteomyelitis treatment were carried out. Microporous nano-hydroxyapatite was prepared by low temperature phosphorization of three-dimensional printed calcium sulfate sample and was impregnated by three types of antibiotics including vancomycin, fosfomycin and gentamicin. Materials properties and antibacterial performance including phase composition, microstructure, degradability, total drug loading, antibacterial activity and shelf life were investigated and reported. Microporous nano-hydroxyapatite having porosity and mean pore size of 63.92% and 0.15 microns was prepared and showed greater resorbability than typical high-temperature sintering samples. Sustained release of antibiotic from the impregnated samples for longer than 29 days was observed, but the difference in the efficiency was related to the difference in the molecular weight, mechanism of action, spectrum of activity of each antibiotic. No deterioration in the antibacterial activity of the prepared antibiotic-impregnated hydroxyapatite was observed after storing for up to 12 months. No cytotoxic potential by MTT assay at all extraction periods was observed for vancomycin-impregnated hydroxyapatite. Gentamicin and fosfomycin impregnated hydroxyapatites showed cytotoxic potential only on day 1 extraction, but no cytotoxic potential was observed on day 2 extraction onward. This could be related to the concentration and characteristics of each released antibiotics.

In Vitro Analysis of Nanoparticulate Hydroxyapatite/Chitosan Composites as Potential Drug Delivery Platforms for the Sustained Release of Antibiotics in the Treatment of Osteomyelitis

Nanoparticulate composites of hydroxyapatite (HAp) and chitosan were synthesized by ultrasound-assisted sequential precipitation and characterized for their microstructure at the atomic scale, surface charge, drug release properties, and combined antibacterial and osteogenic response. Crystallinity of HAp nanoparticles was reduced because of the interference of the surface layers of chitosan with the dissolution/reprecipitation-mediated recrystallization mechanism that conditions the transition from the as-precipitated amorphous calcium phosphate phase to the most thermodynamically stable one—HAp. Embedment of 5–10 nm sized, narrowly dispersed HAp nanoparticles within the polymeric matrix mitigated the burst release of the small molecule model drug, fluorescein, bound to HAp by physisorption, and promoted sustained-release kinetics throughout the 3 weeks of release time. The addition of chitosan to the particulate drug carrier formulation, however, reduced the antibacterial efficacy against Saureus. Excellent cell spreading and proliferation of osteoblastic MC3T3-E1 cells evidenced on microscopic conglomerates of HAp nanoparticles in vitro also markedly diminished on HAp/chitosan composites. Mitochondrial dehydrogenase activity exhibited normal values only for HAp/chitosan particle concentrations of up to 2 mg/cm2 and significantly dropped, by about 50%, at higher particle concentrations (4 and 8 mg/cm2). The gene expression of osteocalcin, a mineralization inductor, and the transcription factor Runx2 was downregulated in cells incubated in the presence of 3 mg/cm2 HAp/chitosan composite particles, whereas the expression of osteopontin, a potent mineralization inhibitor, was upregulated, further demonstrating the partially unfavorable osteoblastic cell response to the given particles. The peak in the expression of osteogenic markers paralleling the osteoblastic differentiation was also delayed most for the cell population incubated with HAp/chitosan particles. Overall, the positive effect of chitosan coating on the drug elution profile of HAp nanoparticles as carriers for the controlled delivery of antibiotics in the treatment of osteomyelitis was compensated for by the lower bacteriostatic efficiency and the comparatively unviable cell response to the composite material, especially at higher dosages.

Increased release time of antibiotics from bone allografts through a novel biodegradable coating.

The use of bone allografts is contraindicated in septic revision surgery due to the high risk of graft reinfection. Antibiotic release from the graft may solve the problem and these combinations can theoretically be used for prevention or even therapy of infection. The present study investigated whether amoxicillin, ciprofloxacin, and vancomycin alone or in combination with chitosan or alginate are suitable for short-term or long-term bone coating. Human bone allografts were prepared from femoral head and lyophilized. Antibiotic coating was achieved by incubating the grafts in antibiotic solution and freeze-drying again. Two biopolymers chitosan and alginate were used for creating sustained-release implantable coatings and the drug release profile was characterized in vitro by spectrophotometry. Using lyophilization with or without chitosan only resulted in short-term release that lasted up to 48 hours. Alginate coating enabled a sustained release that lasted for 8 days with amoxicillin, 28 days with ciprofloxacin coating, and 50 days with vancomycin coating. Using only implantable biodegradable allograft and polymers, a sustained release of antibiotics was achieved with ciprofloxacin and vancomycin for several weeks. Since the calculated daily release of the antibiotic was lower than the recommended IV dose, the calcium alginate coated bone graft can support endoprosthesis revision surgery.

A Study on Electrospun Nanofibrous Mats for Local 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.

Zein/polycaprolactone electrospun matrices for localised controlled delivery of tetracycline.

We report the controlled release of the antibiotic tetracycline (Tet) from triple-layered (3L) electrospun matrices consisting of zein or a zein/PCL blend, where the drug was loaded into the central layer with the two outer layers acting as diffusion barriers. These fibrous matrices successfully encapsulated Tet and efficiently inhibited the growth of a clinical isolate, the methicillin-resistant Staphylococcus aureus strain MRSA252, as demonstrated in a modified Kirby-Bauer disc assay over 5days. Whilst untreated zein fibres are unstable in an aqueous environment, rapidly shrinking due to plasticisation and film formation, blending zein with PCL stabilised the electrospun matrices and prevented them from shrinking. These 3L formulations display sustained antibiotic release and provide a proof of concept for zein-based polymeric matrices as wound dressings to treat or prevent bacterial infection. This is the first demonstration of the controlled release of a clinically used antibiotic from electrospun zein-based matrices.

Preliminary exploration of the development of a collagenous artificial dura mater for sustained antibiotic release

Background Intracranial infection is one of the most common complications of open craniocerebral injury and of conventional craniotomy in neurosurgery. The presence of blood-brain barrier leads to lower drug concentrations in the cerebrospinal fluid than in the venous blood. Increasing the intravenous dosage or frequency carries the risk of systemic adverse reactions or infections in other parts of the body. Developing an artificial dura mater (ADM) for sustained antibiotic release for use during neurosurgery can solve the problems perfectly. Methods Three types of drug-loaded ADMs made of collagen and containing cefuroxime sodium, ceftriaxone sodium, or norvancomycin were prepared. The antibacterial activity and sustained release characteristics of the ADMs were examined using bacteriostatic and release tests. Results Single-layered collagen based ADMs (40 mm×50 mm×5 mm) containing 18 mg cefuroxime sodium or ceftriaxone sodium were not suitable for continued development because of drug preservation and stability issues. Using smaller ADMs (20 mm×30 mm×7 mm), containing 4.86 mg of norvancomycin, with increased collagen density and a three-layered film with two outer drug-free films above and below the antibiotic layer resulted in sustained cumulative release of 2.91 mg (59.9%) of norvancomycin over 72 hours. The similar factor (f2) comparison method proved that products from a same batch were statistically significant similar (f2 &gt;50). Conclusions Artificial ADMs made of collagen can be processed to provide a mature dural repair material for the sustained release of norvancomycin. This system may provide a basis for developing sustained release materials for other drugs.

Killing bacteria within biofilms by sustained release of tetracycline from triple-layered electrospun micro/nanofibre matrices of polycaprolactone and poly(ethylene-co-vinyl acetate).

We report the controlled release of the antibiotic tetracycline (tet) HCl from a triple-layered electrospun matrix consisting of a central layer of poly(ethylene-co-vinyl acetate (PEVA) sandwiched between outer layers of poly-ε-caprolactone (PCL). These micro/nanofibre layers with tet successfully encapsulated (essentially quantitatively at 3 and 5% w/w) in each layer, efficiently inhibited the growth of a panel of bacteria, including clinical isolates, as shown by a modified Kirby-Bauer disc assay. Furthermore, they demonstrated high biological activity in increasingly complex models of biofilm formation (models that are moving closer to the situation in a wound) by stopping biofilm formation, by killing preformed biofilms and killing mature, dense biofilm colonies of Staphylococcus aureus MRSA252. Tet is clinically useful with potential applications in wound healing and especially in complicated skin and skin-structure infections; electrospinning provides good encapsulation efficiency of tet within PCL/PEVA/PCL polymers in micro/nanofibre layers which display sustained antibiotic release in formulations that are anti-biofilm.

Acrylic bone cement: current concept review

Acrylic bone cement has had for years an important role in orthopedic surgery. Polymethylmethacrylate (PMMA) has been extended from the ophthalmological and dental fields to orthopedics, as acrylic cement used for fixation of prosthetic implants, for remodeling osteoporotic, neoplastic and vertebral fractures repair. The PMMA bone cement is a good carrier for sustained antibiotic release in the site of infection. Joint prostheses chronic infection requires surgical removal of the implant, in order to eradicate the infection process. This can be performed in the same surgical time (one-stage procedure) or in two separate steps (two-stage procedure, which involves the use of an antibiotic-loaded cement spacer). The mechanical and functional characteristics of the spacers allow a good joint range of motion, weight-bearing in selected cases and a sustained release of antibiotic at the site of infection. The improvement of fixation devices in recent years was not accompanied by the improvement of elderly bone quality. Some studies have tested the use of PMMA bone cement or calcium phosphate as augmentation support of internal fixation of these fractures. Over the past 20 years, experimental study of acrylic biomaterials (bone cement, bioglass ceramic, cement additives, absorbable cement, antibiotic spacers) has been of particular importance, offering numerous models and projects.