Poly DL-lactide Research Articles

Development of a spray-drying method for the formulation of respirable microparticles containing ofloxacin–palladium complex

The purpose of this study was to produce low-releasing spray-dried polymeric microparticles (MP) useful to target alveolar macrophages in tuberculosis (TB) inhalation therapy. Ofloxacin (Ofx) was encapsulated as ofloxacin-palladium (Ofx-Pd) complex into poly DL-lactide (PLA) MP by spray-drying. Ofx-Pd was prepared according to a method previously reported. A D-optimal design was employed to optimize drug content (DC), aerodynamic diameter (d(ae)) and span. d(ae) was calculated coupling tap-density to particle size analysis. The MP were characterized by SEM, UV spectrophotometry, and DSC. In vitro drug release was performed in comparison to Ofx loaded PLA MP. The Ofx-Pd complex formed spontaneously with a 1:1 stoichiometry. Inlet temperature, drug loading and polymer concentration resulted the most influential. Optimal MP had span of 0.9, a round shape, d(ae) of 2.5 μm, and DC of 30% (w/w). DSC and SEM analyses correlated with particle size. The optimized MP formulation showed a very low release at pH 7.4 compared to spray-dried Ofx loaded MP, the release increased slightly at lower pHs. Potentially inhalable MP were obtained by an optimized spray-drying process. The very low initial drug release at physiologic pH could be useful to target alveolar macrophages and to avoid systemic exposure.

A novel injectable in situ forming poly-DL-lactide and DL-lactide/glycolide implant containing lipospheres for controlled drug delivery

One of the greatest challenges in in situ forming implant (ISFI) systems by polymer precipitation is the large burst release during the first 1–24 hours after implant injection. The aim of this study was to decrease the burst-release effect of a water-soluble model drug, donepezil HCl, with a molecular weight of 415.96 Da, from in situ forming implants using a novel in situ implant containing lipospheres (ISILs). In situ implant suspensions were prepared by dispersing cetyl alcohol and glyceryl stearate lipospheres in a solution of poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG). Also, in situ implant solutions were prepared using different concentrations of PDL or PDLG solutions in N-methyl-2-pyrrolidone (NMP). Triacetin and Pluronic L121 were used to modify the release pattern of donepezil from the in situ implant solutions. In vitro release, rheological measurement, and injectability measurement were used to evaluate the prepared in situ implant formulae. It was found that ISIL decreased the burst effect as well as the rate and extent of drug release, compared to lipospheres, PDL, and PDLG in situ implant. The amount of drug released in the first day was 37.75, 34.99, 48.57, 76.3, and 84.82% for ISIL in 20% PDL (IL-1), ISIL in 20% PDLG (IL-2), lipospheres (L), 20% PDL ISFI (I5), and 20% PDLG ISFI (I8), respectively. The prepared systems showed Newtonian flow behavior. ISIL (IL-1 and IL-2) had a flow rate of 1.94 and 1.40 mL/min, respectively. This study shows the potential of using in situ implants containing lipospheres in controlling the burst effect of ISFI.

Stratified scaffolds for osteochondral tissue engineering applications: Electrospun PDLLA nanofibre coated Bioglass®-derived foams

This work focuses on designing bilayered constructs by combining electrospun poly-DL-Lactide (PDLLA) fibers and Bioglass®-derived scaffolds for development of osteochondral tissue replacement materials. Electrospinning was carried out using a solution of 5 wt/v% PDLLA in dimethyl carbonate. The PDLLA layer thickness increased from 2 to 150 µm with varying electrospinning time. Bioactivity studies in simulated body fluid showed that HA mineralization decreased as the thickness of the PDLLA layer increased. A preliminary in vitro study using chondrocyte cells (ATDC5) showed that cells attached, proliferated and migrated into the fibrous network, confirming the potential applicability of the bilayered scaffolds in osteochondral defect regeneration.

Development and characterization of skin permeation retardants and enhancers: A comparative study of levothyroxine-loaded PNIPAM, PLA, PLGA and EC microparticles

Polymeric microparticles suitable for topical and transdermal delivery systems were studied using poly D,L lactide (PLA), poly D,L lactide co glycoside (PLGA), poly (N-isopropylacrylamide) (PNIPAM) and ethyl cellulose (EC). Drug encapsulation efficacy, microparticle stability and skin permeation studies of levothyroxine loaded microparticles were carried out using excised human skin, and the skin permeation pattern was observed using confocal laser scanning microscopy. It was found that ethyl cellulose microparticles had the highest drug encapsulation and minimal drug leakage during the 14 week storage period. The PNIPAM microparticles had the lowest drug encapsulation efficiency and a fast degradation rate. The PLGA microparticles exhibited a temperature dependent drug leakage. Permeation studies using a flow-through diffusion cell indicated that the polymer transition temperature (T(g)) may influence the skin permeation rate of levothyroxine. Polyesters (PLA and PLGA) and PNIPAM acted as a skin penetration retardant and caused skin accumulation of the drug. These microparticles have potential use in skin formulations containing sunscreens and other active ingredients that are meant to be concentrated on the skin surface. However, skin permeation was observed from EC microparticles, therefore such polymers may be used as carriers in transdermal formulations to help achieve therapeutic concentrations of the drug in the plasma.

THE EFFECT OF RESIDUAL POLY(VINYL ALCOHOL) ON BIOPHYSICAL INTERACTION OF NANOPARTICLES WITH ENDOTHELIAL CELL MODEL MEMBRANE

Poly(vinyl alcohol) (PVA) is commonly used as an emulsifier in the formulation of nanoparticles (NPs) comprising poly DL-lactide co-glycolide and polylactide-based biodegradable polymers for drug and gene delivery applications. A fraction of PVA remains associated with the NPs at the interface despite their repeated washing (residual PVA). We hypothesize that this residual PVA influences the interfacial properties of NPs and hence their biophysical interactions with membrane lipids. In this study, we formulated NPs using PVA of different molecular weights to determine the effects of the residual PVA on biophysical interactions of the formulated NPs with the endothelial cell model membrane using a Langmuir balance. Despite similar physical properties (particle size and zeta potential), NPs formulated with different PVA demonstrated significant variations in their intrinsic surface properties and biophysical interactions with the model membrane. This was evident from the difference in the surface pressure–area (π–A) isotherms prepared in the presence of different formulations of NPs and the change in surface pressure of the model membrane following interaction with NPs. The variation in the biophysical properties was observed even with the NPs formulated using the same molecular weight PVA but obtained from different lots. Since the interfacial properties of NPs can significantly influence NP interactions with cells and tissue, their biophysical characterization could prove to be an important parameter not only to obtain consistent results with NPs but also to optimize their properties for drug/gene delivery applications.

Melt density and flow property of PDLLA/nano-CaCO3 bio-composites

The nanometer calcium carbonate (nano-CaCO3) filled Poly-dl-lactide (PDLLA) bio-composites were prepared with a twin-screw extruder. The melt volume flow rates (MVRs) and melt densities of the composites were measured by means of a melt flow rate instrument under experimental conditions at a temperature range from 180 to 230°C and a load range varying from 2.16 to 10kg. The result showed that the MVRs of the composites increased nonlinearly with a rise in temperature and an increase of load, but decreased linearly with increasing the filler weight fraction. The melt densities of the composites decreased nonlinearly with a rise of temperature, but increased nonlinearly with increasing the load and increased linearly with an addition of the filler weight fraction.

Manufacturing of individual biodegradable bone substitute implants using selective laser melting technique

The additive manufacturing technique selective laser melting (SLM) has been successfully proved to be suitable for applications in implant manufacturing. SLM is well known for metal parts and offers direct manufacturing of three-dimensional (3D) parts with high bulk density on the base of individual 3D data, including computer tomography models of anatomical structures. Furthermore, an interconnecting porous structure with defined and reproducible pore size can be integrated during the design of the 3D virtual model of the implant. The objective of this study was to develop the SLM processes for a biodegradable composite material made of β-tricalcium phosphate (β-TCP) and poly(D, L)-lactide (PDLLA). The development of a powder composite material (β-TCP/PDLLA) suitable for the SLM process was successfully performed. The microstructure of the manufactured samples exhibit a homogeneous arrangement of ceramic and polymer. The four-point bending strength was up to 23 MPa. The X-ray diffraction (XRD) analysis of the samples confirmed β-TCP as the only present crystalline phase and the gel permeations chromatography (GPC) analysis documented a degradation of the polymer caused by the laser process less than conventional manufacturing processes. We conclude that SLM presents a new possibility to manufacture individual biodegradable implants made of β-TCP/PDLLA.

Osteoblast function on electrically conductive electrospun PLA/MWCNTs nanofibers

The electrospinning process was utilized successfully to fabricate the random oriented and aligned electrically conductive nanofibers of biodegradable poly-DL-lactide (PLA) in which multiwalled carbon nanotubes (MWCNTs) were embedded. The topographical features of the composite nanofibers were characterized by SEM. The dispersion and alignment of MWCNTs in nanofiber matrix were observed by TEM. The in vitro degradation was characterized in terms of the morphological change, the mass loss and the reduction of polymer molecular weight as well as the decrease of pH value of degradation media. In particular, these conductive nanofiber meshes offered a unique system to study the synergistic effect of topographic cues and electrical stimulation on osteoblasts outgrowth as a way of exploring their potential application in bone tissue engineering. The results of obsteoblasts assay unstimulated showed that the aligned nanofibers as topographic cues could enhance the extension and direct the outgrowth of obsteoblasts better than random fibers. In the presence of direct current (DC) of 100 μA, the obsteoblasts on all samples grew along the electrical current direction. The cellular elongation and proliferation were mainly dependent on the electrical stimulation whereas the topographical features played a minor role in them. Therefore, electrical stimulation with an appropriate DC value imparted on conductive substrate had great potential in application of bone tissue engineering.

Novel Approach to Creation of Biomimetic Scaffolds for Tissue Engineering

ABSTRACTIn tissue engineering, a successful tissue scaffold is not simply a 3D-micro/nanofibered, highly porous environment that mimics a native extra cellular matrix (ECM). To maintain an ideal medium for cells to grow and proliferate, the biodegradable scaffold should be generally hydrophilic and should serve as a reservoir of cell nutrients, growth factors and other components present in the blood flow. Synthetic biodegradable polymers have found wide applications in micro/nanofibered scaffolding materials because of their proven biocompatibility, availability of established processing techniques, good mechanical properties and controlled, regulated biodegradation time. But, high hydrophobicity of these polymers does not allow to realize a moist environment in the scaffold typical for native ECM and favorable for the cells.We have recently found that electrospun polymeric blends of polyvinylpyrrolidone (PVP) and poly-d,l-lactide (PDLL) provide mechanically strong micro/nanofibered materials of high hydrophilicity. These materials have a regulated absorption ability of blood or other biological liquids of up to ~8-10 g/g without swelling or changing the shape of the fibers. As demonstrated by spectroscopy and differential scanning calorimetry, strong polymer chains assembly of PDLL-PVP occurs when the corresponding blends are processed into micro/nanofibers by electrospinning or casted into films. The polymer chain assembly is not affected by absorbed liquids. The matrices preserve their liquid absorption ability after drying. Preliminary testing of matrices in humans demonstrated a high efficacy of the scaffolds for wound healing acceleration.

Letter to the Editor: Fibroxanthoma: A Complication of a Biodegradable Screw

To the Editor: A recent case report in Clinical Orthopaedics and Related Research used the misleading term “fibroxanthoma” to describe the histologic findings of a biopsy obtained near the site of a previously inserted resorbable polymer screw [7]. Among the polymers currently used in degradable orthopaedic devices are polyglycolic acid (PGA), polylactic acid (PLA), poly-DL-lactide (PDLA), and poly-DL-lactide-co-glycolide (PLGA). The main degradative mechanism for these polymers is hydrolysis [9], a process that eventually releases the base monomers, such as lactic acid or glycolic acid that ultimately are metabolized into carbon dioxide and water. The rate of dissolution of a degradable polymer can be influenced by many factors, including the polymer composition and crystallinity, size of the device, additives, method of sterilization, local pH, and local mechanical factors [8]. The dissolution process leads to reduced polymer chain length, and loss of mechanical strength. If the device breaks into pieces, the larger fragments are relatively inert, but smaller fragments are phagocytosed by macrophages and giant cells. The highest tissue concentration of macrophages and giant cells correlates with the dissolution kinetics of the polymer [4, 6]. The process of biologic resorption is asymptomatic in most patients, but if the degrading polymer is in a subcutaneous location, then the edema and inflammatory reaction can create a mass that will contain macrophages and giant cells [2]; special techniques may be needed to observe fragments of residual polymer. Some cases of tunnel widening and bone resorption also have been associated with degrading polymer screws [3], although this is nonspecific as it also has been reported associated with metal screws [1]. The term “fibroxanthoma” is rarely used nowadays, but usually is considered to be either a synonym for a benign fibrous histiocytoma, or to represent a subset of benign fibrous histiocytomas that contain prominent xanthomatous cells (“foamy” histiocytes) [5]. A fibroxanthoma (ie, benign fibrous histiocytoma) is a mass that, by definition, is not associated with a foreign-body reaction. In the case report, Sadat-Ali and coauthors [7] describe a patient who had a soft tissue swelling develop at the site of the tibial tunnel, 3 years after a biodegradable screw had been used for ACL reconstruction. A biopsy “was sent for histopathologic examination, which resulted in a diagnosis of fibroxanthoma” [7]. Not surprisingly, the cells showed positive staining with CD-68, a marker for macrophages. Correct diagnosis of bone and soft tissue lesions often requires correlation between clinical and histologic findings, and in the context of this patient, the biopsy should not be interpreted as a fibroxanthoma any more than the similar macrophage reaction to a resorbable suture would be considered a fibroxanthoma. Whether this process is viewed as an inflammatory complication, or an expected, transient foreign-body reaction depends on the presence or absence of symptoms [2]. Although the process is asymptomatic and resolves without treatment in most patients, a symptomatic lesion could be associated with screw degradation, and debridement of the screw fragments is expected to be curative.

Nanoencapsulation and characterization of Albizia chinensis isolated antioxidant quercitrin on PLA nanoparticles

The plant isolated antioxidant quercitrin has been encapsulated on poly- d, l-lactide (PLA) nanoparticles by solvent evaporation method to improve the solubility, permeability and stability of this molecule. The size of quercitrin-PLA nanoparticles is 250 ± 68 nm whereas that PLA nanoparticles is 195 ± 55 nm. The encapsulation efficiency of nanoencapsulated quercitrin evaluated by HPLC and antioxidant assay is 40%. The in vitro release kinetics of quercitrin under physiological condition reveals initial burst release followed by sustained release. Less fluorescence quenching is observed with equimolar concentration of PLA encapsulated quercitrin than free quercitrin. The presence of quercitrin specific peaks on FTIR of five times washed quercitrin loaded PLA nanoparticles provides an extra evidence for the encapsulation of quercitrin into PLA nanoparticles. These properties of quercitrin nanomedicine provide a new potential for the use of such less useful highly active antioxidant molecule towards the development of better therapeutic for intestinal anti-inflammatory effect and nutraceutical compounds.

Synthesis, characterization, and molecular recognition of sugar-functionalized nanoparticles prepared by a combination of ROP, ATRP, and click chemistry

The aim of this work was to prepare nanoparticles bearing sugar residues at their surface through the synthesis of amphiphilic block copolymer of poly d,l-lactide (PLA) and poly(ethylene glycol)methacrylate, with the hydrophilic part terminating with glucopyranoside molecules as a model for any carbohydrate ligand. The construction was achieved by a combination of click chemistry, ring-opening polymerization, and atom transfer radical polymerization. The modified monomer and resulting copolymer were characterized by NMR, SEC, and FTIR. Nanoparticles with a mean hydrodynamic diameter of <200 nm as determined by quasi-elastic light scattering were prepared from the amphiphilic copolymer by nanoprecipitation using dimethylformamide (DMF) as water-miscible solvent. In the range of 2.5–10 mg copolymer/mL DMF, the polymer concentration did not have much effect on the size of the nanoparticles. Accessibility of glucopyranoside molecules on the surface of the nanoparticles was confirmed by formation of aggregates from nanoparticles in the presence of concanavalin A observed by transmission electronic microscopy. Finally, no significant cytotoxicity toward human umbilical vein endothelial cells was detected for the final nanoparticles. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3178–3187, 2010

Development of biodegradable nanoparticles for delivery of quercetin

The antioxidant molecule quercetin has been encapsulated on poly- d, l-lactide (PLA) nanoparticles by solvent evaporation method for the improvement of its poor aqueous solubility and stability. The surface morphology and average size of PLA and quercetin loaded PLA nanoparticles are 170 ± 25 and 130 ± 30 nm respectively. The antioxidant activities of the PLA encapsulated quercetin nanomedicine are identical to free quercetin. The nanoencapsulation efficiency of quercetin evaluated by HPLC and antioxidant assay is 96.7%. The in vitro release kinetics under physiological condition show initial burst release followed by slow and sustained release. The complete release and maximum retention of quercetin is 72 and 96 h respectively. The less fluorescence quenching efficiency of quercetin–PLA nanoparticles than free quercetin on BSA confirms the controlled release of quercetin from PLA nanoparticles. These properties of PLA encapsulated quercetin molecule pave way for encapsulating various therapeutically less useful highly active antioxidant molecules towards the development of better therapeutic compounds.

Fabrication and characterization of electrospun poly‐DL‐lactide (PDLLA) fibrous coatings on 45S5 Bioglass® substrates for bone tissue engineering applications

AbstractBACKGROUND: This work focuses on combining electrospun biodegradable poly‐DL‐lactide (PDLLA) fibres and 45S5 Bioglass® for tissue engineering applications.RESULTS: A variety of fibrous structures were produced upon application of an electric field to a flowing solution of PDLLA (5 wt/v%) in di‐methyl carbonate (DMC). Electrospinning was achieved at an applied voltage of 8.5 kV for a fixed flow rate of 5 µL min−1. Scanning electron microscopy images of PDLLA fibres deposited on 45S5 Bioglass® sintered pellets revealed that the fibres had diameters in the range 100–200 nm, leading to increased surface roughness, as assessed by white light interferometry. Bioactivity studies on PDLLA fibre coated Bioglass® substrates were carried out in simulated body fluid (SBF) for 7, 14 and 28 days. It was found that mineralization of PDLLA fibres on 45S5 Bioglass® substrate (formation of hydroxyapatite) occurred after 7 days of immersion in SBF and full coverage of PDLLA fibres with HA nanocrystals was achieved after 14 days in SBF.CONCLUSION: The approach investigated represents a convenient method to develop a controlled mineralized fibrous topography on bioactive glass substrates for improved cell attachment, which can be exploited in bone tissue engineering applications. Copyright © 2009 Society of Chemical Industry

Evaluation of alkyl polyglucoside as an alternative surfactant in the preparation of peptide-loaded nanoparticles

The present study was carried out to evaluate potentials of alkyl polyglucoside (APG) as an alternative surfactant/stabilizer in the preparation of peptide-loaded nanoparticles. hGF2 (human gel filtration fraction 2) was used as a model peptide and APG based on C10 fatty alcohol (decyl polylglucoside) was used as a representative surfactant. PLA (poly D,L-lactide) and PLGA (poly D,L-lactide-co-glycolide) based nanoparticles were prepared and the effect of APG on particle size, entrapment efficiency and biological activity was evaluated. At a concentration as low as 0.05% w/v, APG provided an excellent stabilization effect, resulting in nanoparticles with better encapsulation efficiency and particle size well below 450 nm. The effective concentration of APG was found to be much less (10-fold) as compared to PVA. Moreover, APG also showed low residual content as compared to PVA. In-vitro and in-vivo biological activity evaluation confirmed that encapsulated peptide was compatible with APG. These preliminary results suggest that APGs can be used as alternate surfactants for nanoparticle preparation.

A novel design of one-side coated biodegradable intrascleral implant for the sustained release of triamcinolone acetonide

The purpose of this study was to evaluate the efficacy and safety of biodegradable intrascleral implants for the slow release of triamcinolone acetonide (TA). Intrascleral implant (1 mm thick; 3 mm diameter) was made of PLA (poly( d, l-lactide)) containing 6.4 mg of TA with one-side coating of high molecular weight PLA to render unidirectional drug absorption through the sclera. In vitro TA release was evaluated by liquid chromatography–mass spectroscopy for 90 days. In vivo release of TA was measured in aqueous humor, vitreous, and retina–choroid at 1, 2, 4, 8, and 12 weeks after intrascleral implantation in 20 rabbit eyes. Implant toxicity and biocompatibility were evaluated by slit lamp examinations, indirect ophthalmoscopy, intraocular pressure measurements, electroretinography, and histological examinations. In vitro studies demonstrated that the implants released TA in a controlled manner over 90 days. In vivo, TA was detected in aqueous humor until 4 weeks and in retina–choroid until 8 weeks after implantation, but was detected constantly over 12 weeks in vitreous. No significant retinal toxicity was observed. These results suggest that the devised intrascleral implant offers a promising controlled release system for the delivery of TA to the posterior segment of the eye.

Polyethylenglycol-co-poly-D,L-lactide copolymer based microspheres: Preparation, characterization and delivery of a model protein

Purpose: To prepare and characterize polyethylenglycol-co-poly-D,L-lactide (PEG-D,L-PLA) multiblock copolymer microspheres containing ovalbumin. Microsphere batches made of Poly-D,L-lactide (PLA) homopolymers were prepared in order to evaluate how the presence of PEG segments into PEG-D,L-PLA copolymer could affect the behaviour of microspheres as carrier of protein drugs.Methods: The PEG-D,L-PLA and PLA microspheres, loaded with the model protein ovalbumin, were prepared using double emulsion solvent evaporation method. The effect of PEG segments in the microparticles matrix, on the morphology, size distribution, encapsulation efficiency and release behaviour was studied.Results: According to the results, PEG-D,L-PLA microspheres were more hydrophilic than PLA microparticles and with lower glass transition temperature. The surface of PEG-D,L-PLA microspheres was not as smooth as that of PLA microparticles, the mean diameter of PEG-D,L-PLA microparticles was bigger than that of PLA microspheres. Protein release from the microspheres was affected by the morphological structure of PEG-D,L-PLA microspheres and properties of PEG-D,L-PLA copolymer. This study suggests that PEG-D,L-PLA multiblock copolymer may be used as carrier in protein delivery systems for different purposes.

Early microrecanalization of vas deferens after implantation of biodegradable grafts in rats that previously underwent bilateral vasectomy

Early microrecanalization of vas deferens after implantation of biodegradable grafts in rats that previously underwent bilateral vasectomy

Multiple emulsion microbubbles for ultrasound imaging

In order to improve the sensitivity of ultrasound imaging, the contrast agents, a powerful non-invasive and real-time medical imaging technique, are used. However, air or N 2 or perfluorocarbon only encapsulated microbubbles which are currently used have lower efficiency and short imaging time. So the novel contrast agents with a higher efficiency are required. To achieve this objective, the strategy that we have explored involves the use of superparamagnetic iron oxide (SPIO) Fe 3O 4 nanoparticles multilayer emulsion microbubbles. This multilayer structure consists of three layers. The core is poly- d, l-lactide (PLA) encapsulated N 2 nanobubble with the SPIO nanoparticles forming oil-in-water (W/O) layer. The outermost is water-in-oil-in-water ((W/O)/W) emulsion layer with PVA solution. Herein we describe the synthesis and characterization of ultrasound imaging microstructure with an overall diameter of around 2μm–8μm. On the one hand, the stable gas encapsulated microstructure can provide a high scattering intensity resulting in high echogenicity, On the other hand, SPIO nanoparticles have shown the potential of high-resolution sonography. So the multiple emulsion microbubbles with SPIO can have double action to enhance the ultrasound imaging. Besides, because SPIO can also serve as magnetic resonance imaging (MRI) contrast agents, such microstructure may be useful for multimodality imaging studies in ultrasound imaging and MRI.

Ofloxacin‐delivery system of a polyanhydride and polylactide blend used in the treatment of bone infection

We developed a local drug-release system consisting of two biodegradable polymers, poly(sebacic anhydride) (PSA) and poly-D,L-lactide (PLA), for the treatment of chronic osteomyelitis. PSA and PLA were dissolved and blended at different ratios in tetrahydrofuran. Ofloxacin was loaded with an 8:1 weight ratio of the blend to the drug. The ofloxacin-containing beads of the PSA/PLA blend were made by preheating and compressing them in a mold. The in vitro drug release showed that changing the ratio between the two polymers caused the effective ofloxacin-release duration to vary from 6 to 68 days. The ofloxacin-containing beads with 10% PSA and 90% PLA produced an inhibition zone for the bacteria Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa within 89 days of the experiment. The in vivo drug release of the beads in rabbits demonstrated that the average ofloxacin concentration in the local bone was 20.1 +/- 10.3 microg/g, while that in the plasma was 35.6 +/- 18.8 ng/mL, within 8 weeks. Roentgenography, bacterial cultures, and histological examinations showed that the local release of ofloxacin by the beads could cure osteomyelitis in rabbits. Our findings suggested that using PSA/PLA blends with different ratios as carriers for antibiotics might be useful in the treatment of chronic osteomyelitis and in the prophylaxis of bone infection.