Effect of glycolide monomer on release behavior of gentamicin sulfate-loaded PLGA microparticles (original) (raw)
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2012
Antibiotic treatment of orthopaedic infection is complicated by systemic toxicity and the need of effective therapeutic concentration necessary to ensure optimum killing of bacteria. To overcome the problem of systemic toxicity and to achieve a high initial release followed by sustained release of antibiotics, a new method of delivering gentamicin is attempted by encapsulating gentamicin into PLGA using multiple emulsion, solventevaporation method. Gentamicin was first extracted from the microspheres and quantified using ninhydrin assay before the concentration was measured using UV spectrophotometer. Gentamicin efficacy after encapsulation was preserved when CTAB (83.51 ± 1.42%) and low molecular weight (LMW) PLGA (82.38 ± 9.08%) were used as indicated by drug loading efficiency of more than 80% in the disc-diffusion assay. LMW PLGA enabled high burst release (~90%) of gentamicin within the first 10 hours corresponding to zone inhibition of 13.78 ± 0.86 mm, only 30% smaller than the positive control (10 mg/ml gentamicin). The effects of Tg
Drug Invention Today, 2013
Objective: Osteomyelitis is a multibacterial bone infection which is still remains challenging and difficult to treat, despite of advances in antibiotics and new operative techniques. Present study aims at formulating Gentamicin implants in treatment of Osteomyelitis & other bone infections using glyceryl monostearate (GMS) matrices as a carrier. Methods: Gentamicin implants were prepared by using combination of glyceryl monostearate and poly ethylene glycol as hydrophobic biodegradable sustained release matrices along with different percentage of Sorbitol and Tween80 as erosion enhancers. Several formulations were prepared (K1eK7) by melt granulation followed by compression to form disc shaped implants. The prepared formulations were evaluated for different in vitro parameters & optimized formulation was subjected to in vivo study. Results & discussion: Formulation K4 shows excellent cumulative drug release profile and it does not completely lose its physical shape even after 28 days thus this formulation conclude to be optimum formulation among the all GMS based implant formulations. Also optimized GMS based implant does not show any severe signs of inflammation and other foreign body reactions in laboratory animals, thus it was concluded that GMS based implant have acceptable biological compatibility even after 28 days. Conclusion: Therefore from this study it is proved that, the glyceryl monostearate based implants have potential to retard the drug release for more than five weeks in the treatment of osteomyelitis & bone infections.
Gentamicin loaded PLGA nanoparticles as local drug delivery system for the osteomyelitis treatment
Acta of bioengineering and biomechanics / Wrocław University of Technology, 2015
Since there are more and more cases of multiresistance among microorganisms, rational use of antibiotics (especially their systemic vs. local application) is of great importance. Here we propose polymeric nanoparticles as locally applied gentamicin delivery system useful in osteomyelitis therapy. Gentamicin sulphate (GS) was encapsulated in the poly(lactide-co-glycolide) (PLGA 85:15) nanoparticles by double emulsification (water/oil/water, W1/O/W2). The nanoparticles were characterized by dynamic light scattering, laser electrophoresis and atomic force microscopy. UV-vis spectroscopy (O-phthaldialdehyde assay, OPA) and Kirby-Bauer tests were used to evaluate drug release and antimicrobial activity, respectively. Physicochemical characterization showed that size, shape and drug solubilization of the nanoparticles mainly depended on GS content and concentration of surface stabilizer (polyvinyl alcohol, PVA). Laser electrophoresis demonstrated negative value of zeta potential of the na...
Materials Science and Engineering: C, 2016
Bone scaffolds are susceptible for bacterial infection when implanted, particularly in compromised bone. Therefore anti-bacterial bone scaffolds are desirable. Here a novel approach to provide bactericidal properties for titanium dioxide scaffolds is proposed. Gentamicin loaded poly(L-lactide-co-glycolide) microparticles were immobilized on the scaffold pore walls by sodium alginate hydrogel. The results show that the microparticles were effectively immobilized on the scaffolds. Desired burst release was observed within the first 8 h and gentamicin dose reached 125 μg from single scaffold that corresponded to~25% of total drug introduced in the system. Following the initial burst, the dose was gradually decreasing up to day 10 and afterwards a sustained release of 3 μg/day was measured. Cumulatively~90% of the drug was delivered up to day 50. Above pattern, i.e. burst release with following sustained release, is desired for prevention of perioperative bone infections: burst release stops local infections during post-implantation "decisive period" while further sustained drug release prevents bacterial recolonization. In vitro studies confirmed antimicrobial activity of released gentamicin against Staphylococcus spp. and cytocompatibility of the system with osteoblast-like cells (MG-63). Thus the system is a viable option for the treatment of bone tissue defects.
Journal of Controlled Release, 2005
Osteomyelitis is an infection of the bone, and successful treatment involves local administration for about 6 weeks. Gentamicin is a very hydrophilic drug and tends to come out into the water phase when microspheres are fabricated using solvent evaporation method. Hence, spray drying is an option, and it was observed that the release rate tends to be fast when the particle size is small and large particles cannot be prepared by spray drying. In an effort to get better encapsulation efficiency and release rate, we have worked on the possibility of compressing the microspheres into discs and modifying the porosity of the discs by using biocompatible materials like polyethylene glycol (PEG) and calcium phosphates and also on the fabrication of double-walled and composite microspheres. In the case of microspheres, two methods of fabrication both based on solvent evaporation method were employed. The two polymers used are poly-l-lactide (PLLA) and copolymers of polydl-lactic-co-glycolic acid (PLGA). One method is based on the spreading coefficient theory for the formation of doublewalled microspheres by using single solvent, while the other is based on the property of PLLA not being soluble in ethyl acetate (EA). Characterization to check if the microspheres formed are double-walled was performed. The fabrication method where two solvents, dichloromethane (DCM) and ethyl acetate, were used gave double-walled microspheres, while the other where only dichloromethane was used gave composites. The double-walled microspheres were smaller in size compared to the composites, which were in the range of 100-600 Am. This can be attributed to the difference in the fabrication procedure. We were able to achieve better encapsulation efficiencies of more than 50% and slower release rates, which lasted for about 15 days. It was observed that size played a major role in the encapsulation efficiency and release rates. The possibility of 0168-3659/$ -see front matter D Journal of Controlled Release 102 (2005) 345 -359 www.elsevier.com/locate/jconrel achieving better results by studying the effect of concentration of polymer in solvent and the effect of using different polymers was investigated. D
Gentamicin extended release from an injectable polymeric implant
Journal of Controlled Release, 2007
Gentamicin sulfate, a potent antibiotic agent, is currently used for treatment of osteomyelitis mainly by intravenous injection with a long-term indwelling catheter, local implant of antibiotic containing polymethylmethacrylate beads or calcium phosphate (bone cements). Searching for more effective treatments, this study was designed to evaluate biodegradable injectable gelling polymeric devices for the controlled release of gentamicin sulfate in the treatment of invasive bacterial infections. Gentamicin sulfate was incorporated in poly(sebacic-co-ricinoleic-esteranhydride P(SA-RA)) paste at 10-20% w/w and its release in buffer solution was monitored. The in vitro activity of the formulations was determined against Staphylococcus aureus. A constant release of active gentamicin for over 28 days was found. The stability of the formulation was determined under different storage conditions. The formulations were stable to sterilization by γ-irradiation and long term storage under freezing. The toxicity of the polymer and the formulations with gentamicin was examined by subcutaneous injection to rats. Four weeks after implantation, histopathological examination of the tissues surrounding the implant showed no inflammation. A preliminary study revealed positive effect of gentamicin containing P(SA-RA) on established osteomyelitis in a rat model. In conclusion this study suggests that poly(sebacic-coricinoleic-ester-anhydride) 3:7 loaded with 10%-20% gentamicin sulfate, might be used as an injectable biodegradable device for in situ treatment of osteomyelitis induced by S. aureus.
Current Health Sciences Journal, 2017
ABSTRACT: Purpose-Osteomyelitis is a bone infection that appears as a complication after a fracture or orthopedic surgery. Ciprofloxacin is a broad spectrum antibiotic that can be used in local drug delivery systems for the treatment of bone related infections due to its bactericidal activity against both Gram-negative and Gram-positive bacteria. The purpose of the present study was to include ciprofloxacin in poly (lactic-co-glycolic acid) (PLGA) microspheres. Material and methods-Microspheres were prepared by both water/oil/water (w/o/w) solvent evaporation method and solid/oil/water (s/o/w) dispersion solvent evaporation method. The obtained microspheres were characterized by Fourier Transform Infrared Spectroscopy. High performance liquid chromatography method was deployed to determine the encapsulation ratio. Results-The solvent evaporation method chosen for this experiment resulted in microspheres with good entrapment efficiency. Furthermore the microspheres obtained by the s/...
Journal of Microencapsulation, 2003
Chronic osteomyelitis is still the cause of many problems in orthopaedics in terms of therapy and infection persistence. Four-to-six week systemic antibiotic therapy is required along with bone and soft tissue debridement in the therapy of chronic osteomyelitis. Prolonged-release local antibiotic therapy has been taken into consideration due to the side effects encountered in long-term high dose antibiotic use and the duration of hospitalization of the patients. Although local antibiotic therapy has been achieved by bone cement, a second surgical operation is needed for the removal of the system. On the other hand, heat generation during cement curing limits the use of heat-sensitive active ingredients. The most frequent osteomyelitis inducing microorganism is gram (þ) Staphylococcus aureus. In this study, teicoplanin, a glycopeptide antibiotic, active on gram (þ) bacteria, was incorporated in a synthetic polymer in order to prepare a microsphere formulation for implantation to bone defects. Particle size, surface characteristics, loading capacity and in vitro release characteristics of the microspheres were determined as well as stability assessment of teicoplanin under accelerated conditions. In vivo studies were performed on rabbits and the microparticles were implanted intra-articularly to the lateral condylus of the femur. Antibiotic presence was detected by a microbiological assay from synovial fluid sample aspirated throughout 5 weeks. In the light of these evaluations, microspheres prepared from PLGA (75:25) (Mw 136 000) polymer were determined to be effective, and promising for obtaining prolonged local antibiotic release.
International Journal of Drug Delivery Technology, 2019
Gentamicin sulfate is a broad-spectrum aminoglycoside antibiotic that can be used for primary and secondary infections of the skin. Microspheres can be used to extend drug release on the skin; the resulting therapeutic effect is constant and has a longer duration of action. Therefore it can reduce the frequency of use and increase patient compliance. This study investigated the appropriate profile and release kinetics model of gentamicin sulfate microspheres entrapped on the emulgel base. Gentamicin-alginate microspheres were made by the ionotropic gelation method with aerosolization technique, using 2.5% Na-alginate low viscosity, CaCl2 solution of 1.5M as a crosslinker, maltodextrin as lyoprotectant and were dried using the freeze-drying method. The result of microspheres characterization, gentamicin microsphere was spherical with smooth surface structure and had particle diameter of 3.021 ± 0.017μm. Gentamicin microspheres had moisture content 2.89%, and maximum swelling index wa...
The release of cefazolin and gentamicin from biodegradable PLA/PGA beads
International Journal of Pharmaceutics, 2004
Infection has been one of the most common causes of problems and complications after the operation despite the advance in surgical techniques and the availability of newly developed antibiotics. Local antibiotic delivery beads for treatment of various surgical infections had been studied recently especially in osteomyelitis. This current paper used cefazolin sodium and gentamicin sulfate combined with biodegradable polymers (50:50 poly(dl-lactide):co-glycolide) as antibiotic beads for a long-term drug release. To manufacture an antibiotic bead, polylactide-polyglycolide copolymers were mixed with the antibiotics. The mixture was compressed and sintered at 55 • C to form beads of different sizes. The beads were placed in 3 ml of phosphate buffered saline and incubated at 37 • C. An elution method combined with a bacterial inhibitory test was employed to characterize the release rate of the antibiotics over a 30-day period. The results suggested that the biodegradable beads released high concentrations of antibiotic (well above the minimum inhibitory concentration) in vitro for the period of time needed to treat bone infection; i.e. 2-4 weeks. This provides advantages as a first line choice of long-term antibiotics for patients with osteomyelitis and various infections such as thoracic, abdominal, and pelvic infections, as well as for the prophylaxis of these infections.