Antibiotic in vivo/in vitro release, histocompatibility and biodegradation of gentamicin implants based on lactic acid polymers and copolymers

Schmidt, Carsten; Wenz, R.; Nies, Berthold; Moll, F.

doi:10.1016/0168-3659(95)00067-i

Cited by 61 publications

(39 citation statements)

References 15 publications

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“…Drug diffusion can be impeded by the presence of biofilms and necrotic tissue, for example, which can severely limit the effectiveness of antibiotics. 4 Total and rapid release of gentamicin from collagen sponges have been reported in 60 min in vitro, leading to high local tissue concentrations (e.g. 2000 lg/mL) within 24 h of implantation.…”

Section: Discussionmentioning

confidence: 99%

“…Systemic administration can also pose problems of toxicity to bystander tissues. 1,2 Controlled delivery of antibiotics from a variety of polymeric and inorganic vehicles [3][4][5][6][7] has therefore been widely investigated with the aim of maintaining high, nontoxic, and local concentrations without producing adverse systemic effects. Natural and synthetic polymer fibers are used extensively for soft tissue repair in the form of sutures, vascular grafts, and meshes.…”

Section: Introductionmentioning

confidence: 99%

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Controlled release of an antibiotic, gentamicin sulphate, from gravity spun polycaprolactone fibers

Chang

Lau

Chen

et al. 2007

J Biomedical Materials Res

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The antibiotic, gentamicin sulphate (GS), was incorporated in gravity-spun polycaprolactone (PCL) fibers by spinning from particulate suspensions of the drug in PCL solution to produce a controlled delivery system. The production rate of GS-loaded PCL fibers was confined to the range 1-1.5 m/min and the fiber diameter to 170-220 microm. The kinetics of drug release could be adjusted by varying the GS loading of the fibers and the suspension preparation conditions. Gradual release of approximately 80% of the initial GS content was measured in phosphate buffered saline at 37 degrees C over 50 days from fibers spun from nonhomogenized suspensions, whereas loss of this amount of antibiotic occurred in less than 10 days from fibers spun from homogenized suspensions. Studies of growth inhibition of Stapyhlococcus epidermidis in culture indicated that GS released after 2 weeks from PCL fibers retained antibacterial activity. This behavior recommends further investigation of PCL fibers for local delivery of antibiotics to combat infection associated with periodontal disease, musculoskeletal injuries, and implantation of fiber-based tissue substitutes such as vascular prostheses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Controlled release of an antibiotic, gentamicin sulphate, from gravity spun polycaprolactone fibers

Chang

Lau

Chen

et al. 2007

J Biomedical Materials Res

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“…The scaffold material had fully degraded at 13 weeks, as was seen by Schmidt et al (1995) in the subcutaneous pouches of rats. Ideally, the degradation rate of bone graft material should match the rate of the bone growth (Vaccaro, 2002;Wenisch et al, 2003).…”

Section: Discussionmentioning

confidence: 88%

A biodegradable antibiotic-impregnated scaffold to prevent osteomyelitis in a contaminated in vivo bone defect model

McLaren

White²,

Cox³

et al. 2014

eCM

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Open fractures are at risk of serious infection and, if infected, require several surgical interventions and courses of systemic antibiotics. We investigated a new injectable formulation that simultaneously hardens in vivo to form a porous scaffold for bone repair and delivers antibiotics at high concentrations to the local site of infection. Duration of antimicrobial activity against Staphylococcus aureus was determined using the serial plate transfer test. Ultimate compressive strength and porosity of the material was measured with and without antibiotics. The material was evaluated in vivo in an ovine medial femoral condyle defect model contaminated with S. aureus. Sheep were sacrificed at either 2 or 13 weeks and the defect and surrounding bone assessed using micro-computed tomography and histology. Antimicrobial activity in vitro persisted for 19-21 days. Sheep with antibiotic-free material and bacteria became infected, while those with antibiotic-containing material and bacteria did not. Similarly, new bone growth was seen in uninoculated animals with plain polymer, and in those with antibiotic polymer with bacteria, but not in sheep with plain polymer and bacteria. The antibiotic-impregnated scaffolds were effective in preventing S. aureus infections whilst supporting bone growth and repair. If translated into clinical practice, this approach might reduce the need for systemic antibiotics.

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“…[50][51][52][53][54][55] Other authors focused on biodegradable polymers [such as PLA, PLLA, PDLLA, PGA, phosphate-PLA, and poly-lactide-co-glycolide (PLGA)], polyanhydride, collagen, Chitosan, and polyhydroxyalkanoate as carriers of antibacterial substances. [56][57][58][59][60][61][62][63][64][65][66][67][68][69] In all the investigations so far, the only antibacterial substances to be integrated into the ''slow-release systems'' were various antibiotics. To our knowledge, the integration of an antiseptic substance into any sort of ''slow-release system' ' has not yet been reported in the published literature.…”

Section: Discussionmentioning

confidence: 99%

Effect on infection resistance of a local antiseptic and antibiotic coating on osteosynthesis implants: An in vitro and in vivo study

Kälicke

Schierholz

Schlegel

et al. 2006

Journal Orthopaedic Research

108

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The purpose of this study was to acquire information about the effect of an antibacterial and biodegradable poly-L-lactide ( PLLA) coated titanium plate osteosynthesis on local infection resistance. For our in vitro and in vivo experiments, we used six-hole AO DC minifragment titanium plates. The implants were coated with biodegradable, semiamorphous PLLA (coating about 30 mm thick). This acted as a carrier substance to which either antibiotics or antiseptics were added. The antibiotic we applied was a combination of Rifampicin and fusidic acid; the antiseptic was a combination of Octenidin and Irgasan. This produced the following groups: Group I: six-hole AO DC minifragment titanium plate without PLLA; Group II: six-hole AO DC minifragment titanium plate with PLLA without antibiotics/antiseptics; Group III: six-hole AO DC minifragment titanium plate with PLLA þ 3% Rifampicin and 7% fusidic acid; Group IV: six-hole AO DC minifragment titanium plate with PLLA þ 2% Octenidin and 8% Irgasan. In vitro, we investigated the degradation and the release of the PLLA coating over a period of 6 weeks, the bactericidal efficacy of antibiotics/ antiseptics after their release from the coating and the bacterial adhesion of Staphylococcus aureus to the implants. In vivo, we compared the infection rates in white New Zealand rabbits after titanium plate osteosynthesis of the tibia with or without antibacterial coating after local percutaneous bacterial inoculations at different concentrations (2 Â 10 5 -2 Â 10 8 ): The plate, the contaminated soft tissues and the underlying bone were removed under sterile conditions after 28 days and quantitatively evaluated for bacterial growth. A stepwise experimental design with an ''up-anddown'' dosage technique was used to adjust the bacterial challenge in the area of the ID50 (50% infection dose). Statistical evaluation of the differences between the infection rates of both groups was performed using the two-sided Fisher exact test ( p < 0.05). Over a period of 6 weeks, a continuous degradation of the PLLA coating of 13%, on average, was seen in vitro in 0.9% NaCl solution. The elution tests on titanium implants with antibiotic or antiseptic coatings produced average release values of 60% of the incorporated antibiotic or 62% of the incorporated antiseptic within the first 60 min. This was followed by a much slower, but nevertheless continuous, release of the incorporated antibiotic and antiseptic over days and weeks. At the end of the test period of 42 days, 20% of the incorporated antibiotic and 15% of the incorporated antiseptic had not yet been released from the coating. The antibacterial effect of the antibiotic/antiseptic is not lost by integrating it into the PLLA coating. The overall infection rate in the in vivo investigation was 50%. For Groups I and II the infection rate was both 83% (10 of 12 animals). In Groups III and IV with antibacterial coating, the infection rate was both 17% (2 of 12 animals). The ID50 in the antibacterial coated Groups III and IV was recorded ...

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Antibiotic in vivo/in vitro release, histocompatibility and biodegradation of gentamicin implants based on lactic acid polymers and copolymers

Cited by 61 publications

References 15 publications

Controlled release of an antibiotic, gentamicin sulphate, from gravity spun polycaprolactone fibers

Controlled release of an antibiotic, gentamicin sulphate, from gravity spun polycaprolactone fibers

A biodegradable antibiotic-impregnated scaffold to prevent osteomyelitis in a contaminated in vivo bone defect model

Effect on infection resistance of a local antiseptic and antibiotic coating on osteosynthesis implants: An in vitro and in vivo study

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