Vancomycin encapsulation in biodegradable poly(ε-caprolactone) microparticles for bone implantation. Influence of the formulation process on size, drug loading, in vitro release and cytocompatibility

Ray, Anne‐Marie Le; Chiffoleau, S; Iooss, P; Grimandi, G.; Gouyette, Alain; Daculsi, Guy; Merle, Christian

doi:10.1016/s0142-9612(02)00357-5

Cited by 80 publications

(21 citation statements)

References 34 publications

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“…The same results were observed using the gel diluted with fresh medium (50 and 30%). These results clearly show that PCL‐SA gel is cytocompatible and are in agreement with results from alternative studies using pure PCL with different cell culture 47–50…”

Section: Resultssupporting

confidence: 90%

Biocompatibility and biodegradation of polycaprolactone‐sebacic acid blended gels

Salgado

Sánchez

Zavaglia

et al. 2011

J Biomedical Materials Res

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Tissue engineering aims at creating biological body parts as an alternative for transplanting tissues and organs. A current new approach for such materials consists in injectable biodegradable polymers. Their major advantages are the ability to fill-in defects, easy incorporation of therapeutic agents or cells, and the possibility of minimal invasive surgical procedures. Polycaprolactone (PCL) is a promising biodegradable and elastic biomaterial, with the drawback of low-degradation kinetics in vivo. In this work a biodegradable injectable gel of PCL blended with sebacic acid (SA) was prepared, to improve the degradation rate of the biomaterial. SA is known for its high degradation rate, although in high concentrations it could originate a pH decrease and thus disturb the biocompatibility of PCL. Degradation tests on phosphate buffered saline were carried out using 5% of SA on the blend and the biomaterial stability was evaluated after degradation using differential scanning calorimetry, dynamical mechanical analysis, and scanning electronic microscopy. After degradation the elastic properties of the blend decreased and the material became more crystalline and stiffer, although at a lower extent when compared with pure PCL. The blend also degraded faster with a loss of the crystalline phase on the beginning (30 days), although its thermal and mechanical properties remained comparable with those of the pure material, thus showing that it achieved the intended objectives. After cell assays the PCL-SA gel was shown to be cytocompatible and capable of maintaining high cell viability (over 90%).

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Section: Resultssupporting

confidence: 90%

Biocompatibility and biodegradation of polycaprolactone‐sebacic acid blended gels

Salgado

Sánchez

Zavaglia

et al. 2011

J Biomedical Materials Res

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“…Lactic acid polymers, derived from the polymerization of lactic acid at various molecular weights10–13 or as copolymers of polylactide and polyglycolide acid12, 14–17 have been studied as potential bioresorbable carriers of antibacterial agents. A number of studies have been focused on the use of polycaprolactone,19–21 which is a biodegradable aliphatic polyester belonging to the same family as polylactid acid and polyglycolic acid. The same substances have been applied in attempts to treat experimental osteomyelitis 5, 14, 18, 39, 40.…”

Section: Discussionmentioning

confidence: 99%

“…Several resorbable materials such as collagen,8 gelatin,9 polymers in different chemistries (polylactides,10–13 copolymers of lactide and glycolide,12, 14–17 polyanhydrides,18 and polycaprolactone,19–21), biodegradable bone cements,22, 23 hydroxyapatite and glass ceramics,24–27 calcium sulfate,28 and fibrin sealant implants29 have been investigated for use of drug delivery systems of various antibiotics. Limited clinical reports are available from collagen–gentamicin sponge,8 and antibiotic impregnated calcium phosphate 30.…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo testing of bioabsorbable antibiotic containing bone filler for osteomyelitis treatment

Koort

Suokas

Veiranto

et al. 2006

J Biomedical Materials Res

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The use of local antibiotics from a biodegradable implant is appealing concept for treatment of chronic osteomyelitis. Our aim was to develop a new drug delivery system based on controlled ciprofloxacin release from poly(D/L-lactide). Cylindrical composite pellets (1.0 x 0.9 mm) were manufactured from bioabsorbable poly(D/L-lactide) matrix and ciprofloxacin (7.4 wt %). In vitro studies were carried out to delineate the release profile of the antibiotic and to verify its antimicrobial activity by means of MIC testing. A long-term study in rabbits was performed to validate the release of ciprofloxacin from the composite in vivo. Therapeutic level of ciprofloxacin (>2 microg/mL) was maintained between 60 and 300 days and the concentration remained below the potentially detrimental level of 20 microg/mL in vitro. The released ciprofloxacin had retained its antimicrobial properties against common pathogens. In an exploratory long-term in vivo study with three rabbits, ciprofloxacin could not be detected from the serum after moderate filling (160 mg) of the tibia (follow-up 168 days), whereas after high dosing (a total dose of 1,000 mg in both tibias) ciprofloxacin was found temporarily at low serum concentrations (14-34 ng/mL) during the follow-up of 300 days. The bone concentrations of ciprofloxacin could be measured in all samples at 168 and 300 days. The tested copolylactide matrix seems to be a promising option in selection of resorbable carriers for sustained release of antibiotics, but the composite needs modifications to promote ciprofloxacin release during the first 60 days of implantation.

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“…Microparticle size is an important factor that affects the choice of administration route (10–12), drug encapsulation within the microparticle and therefore drug release profile from the delivery vehicle (13–15). Another common problem with spray drying and emulsion-based methods is low drug loading, often with an average of less than 10% (16–18). Certainly there is room for improvement in microencapsulation techniques.…”

Section: Introductionmentioning

confidence: 99%

Microparticles produced by the hydrogel template method for sustained drug delivery

Lü

Sturek

Park

2014

International Journal of Pharmaceutics

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Polymeric microparticles have been used widely for sustained drug delivery. Current methods of microparticle production can be improved by making homogeneous particles in size and shape, increasing the drug loading, and controlling the initial burst release. In the current study, the hydrogel template method was used to produce homogeneous poly(lactide-co-glycolide) (PLGA) microparticles and to examine formulation and process-related parameters. Poly(vinyl alcohol) (PVA) was used to make hydrogel templates. The parameters examined include PVA molecular weight, type of PLGA (as characterized by lactide content, inherent viscosity), polymer concentration, drug concentration and composition of solvent system. Three model compounds studied were risperidone, methylprednisolone acetate and paclitaxel. The ability of the hydrogel template method to produce microparticles with good conformity to template was dependent on molecular weight of PVA and viscosity of the PLGA solution. Drug loading and encapsulation efficiency were found to be influenced by PLGA lactide content, polymer concentration and composition of the solvent system. The drug loading and encapsulation efficiency were 28.7% and 82% for risperidone, 31.5% and 90% for methylprednisolone acetate, and 32.2 % and 92 % for paclitaxel, respectively. For all three drugs, release was sustained for weeks, and the in vitro release profile of risperidone was comparable to that of microparticles prepared using the conventional emulsion method. The hydrogel template method provides a new approach of manipulating microparticles.

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Vancomycin encapsulation in biodegradable poly(ε-caprolactone) microparticles for bone implantation. Influence of the formulation process on size, drug loading, in vitro release and cytocompatibility

Cited by 80 publications

References 34 publications

Biocompatibility and biodegradation of polycaprolactone‐sebacic acid blended gels

Biocompatibility and biodegradation of polycaprolactone‐sebacic acid blended gels

In vitro and in vivo testing of bioabsorbable antibiotic containing bone filler for osteomyelitis treatment

Microparticles produced by the hydrogel template method for sustained drug delivery

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