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Biodegradable vancomycin-eluting poly[(d,l)-lactide-co-glycolide] nanofibres for the treatment of postoperative central nervous system infection.

ABSTRACT: The incidence of postoperative central nervous system infection (PCNSI) is higher than 5%-7%. Successful management of PCNSI requires a combined therapy of surgical debridement and long-term antibiotic treatment. In this study, Duraform soaked in a prepared bacterial solution was placed on the brain surface of rats to induce PCNSI. Virgin poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibrous membranes (vehicle-control group) and vancomycin-eluting PLGA membranes (vancomycin-nanofibres group) were implanted. The wound conditions were observed and serial brain MRI and pathology examinations were performed regularly. PCNSI was consistently induced in a single, simple step. In the vehicle-control group, most rats died within 1 week, and the survival rate was low (odds ratio = 0.0357, 95% confidence interval = 0.0057-0.2254). The wounds and affected cerebral tissues necrosed with purulence and increased in mass from the resulting PCNSI volumes. Initially, the mean PCNSI volumes showed no significant difference between the two groups. The PCNSI volume in the rats in the vancomycin-nanofibres group significantly decreased (P < 0.01), and the wound appearance was excellent. Pathologic examinations revealed that the necrosis and leukocyte infiltration area decreased considerably. The experimental results suggest that vancomycin-eluting PLGA nanofibres are favourable candidates for treating PCNSI after surgical debridement.

SUBMITTER: Tseng YY

PROVIDER: S-EPMC4297986 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:Fluorescent biomaterials have attracted significant research efforts in the past decades. Herein, we report a new series of biodegradable, fluorescence imaging-enabled copolymers, biodegradable photoluminescent poly(lactide-co-glycolide) (BPLP-co-PLGA). Photoluminescence characterization shows that BPLP-co-PLGA solutions, films and nanoparticles all exhibit strong, tunable and stable photoluminescence. By adjusting the molar ratios of L-lactide (LA)/glycolide (GA) and (LA+GA)/BPLP, full degradation of BPLP-co-PLGA can be achieved in 8-16 weeks. The fluorescence decay behavior of BPLP-co-PLGA can be used for non-invasive monitoring of material degradation. In vitro cytotoxicity and in vivo foreign body response evaluations demonstrate that BPLP-co-PLGA exhibits similar biocompatibility to poly(lactide-co-glycolide) (PLGA). The imaging-enabled BPLP-co-PLGA was fabricated into porous scaffolds whose degradation can be monitored through non-invasive imaging and nanoparticles that show theranostic potential demonstrated by fluorescent cellular labeling, imaging and sustained 5-fluorouracil delivery. The development of inherently fluorescent PLGA copolymers is expected to impact the use of already widely accepted PLGA polymers for applications where fluorescent properties are highly desired but limited by the conventional use of cytotoxic quantum dots and photobleaching organic dyes.Statement of significanceThis manuscript describes a novel strategy of conferring intrinsic photoluminescence to the widely used biodegradable polymers, poly(lactide-co-glycolide) without introducing any cytotoxic quantum dots or photo-bleaching organic dyes, which may greatly expand the applications of these polymers in where fluorescent properties are highly desired. Given the already significant impact generated by the use of PLGA and alike, this work contributes to fluorescence chemistry and new functional biomaterial design and will potentially generate significant impact on many fields of applications such as tissue engineering, molecular imaging and labeling, and drug delivery.

Project description:This methodology permits to simulate the performance of different Poly(D,L-lactide-co-glycolide) copolymer formulations (PDLGA) in the human body, to identify the more influencing variables on hydrolytic degradation and, thus, to estimate biopolymer degradation level. The PDLGA characteristic degradation trends, caused by hydrolysis processes, have been studied to define their future biomedical applications as dental scaffolds. For this purpose, the mass loss, pH, glass transition temperature (Tg) and absorbed water mass of the different biopolymers have been obtained from samples into a phosphate-buffered saline solution (PBS) with initial pH of 7.4, at 37°C (human body conditions). The mass loss has been defined as the variable that characterize the biopolymer degradation level. Its dependence relationship with respect to time, pH and biopolymer formulation has been modelled using statistical learning tools. Namely, generalized additive models (GAM) and nonlinear mixed-effects regression with logistic and asymptotic functions have been applied. GAM model provides information about the relevant variables and the parametric functions that relate mass loss, pH and time. Mixed effects are introduced to model and estimate the degradation properties, and to compare the PDLGA biopolymer populations. The degradation path for each polymer formulation has been estimated and compared with respect to the others for helping to use the proper polymer for each specific medical application, performing selection criteria. It was found that the mass loss differences in PDLGA copolymers are strongly related with the way the pH decay versus time, due to carboxylic acid groups formation. This may occur in those environments in which the degradation products remain relatively confined with the non degraded mass. This is the case emulated with the present experimental procedure. The results show that PDLGA polymers degradation degree, in terms of half life and degradation rate, is increasing when acid termination is included, when DL-lactide molar ratio is reduced, decreasing the midpoint viscosity, or when glycolide is not included.

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Biodegradable vancomycin-eluting poly[(d,l)-lactide-co-glycolide] nanofibres for the treatment of postoperative central nervous system infection.

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