Dataset Information

Poly(l-lactide)-Based Anti-Inflammatory Responsive Surfaces for Surgical Implants.

ABSTRACT: In the last few decades, surgical implants have been widely used to restore the function of damaged bones or joints. However, it is essential to receive antibiotic or anti-inflammatory treatment to circumvent significant problems associated, such as the colonization of the implanted surface by bacteria or other microorganisms and strong host inflammatory responses. This article presents the effectiveness of the copper catalyzed alkyne-azide cycloaddition (CuAAC) ("click") reaction by the linkage of a fluorophore to the poly(L-lactide) (PLLA) surface. The results were analysed by means of X-ray photoelectron spectroscopy (XPS), contact angle and fluorescence microscopy. Moreover, this current work describes the covalent immobilization of the anti-inflammatory drug indomethacin on a PLLA surface. The CuAAC click reaction was selected to anchor the drug to the polymeric films. The successful bioconjugation of the drug was confirmed by XPS and the change on the contact angle.

SUBMITTER: Sanchez-Bodon J

PROVIDER: S-EPMC7794694 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Poly(l-lactide)-Based Anti-Inflammatory Responsive Surfaces for Surgical Implants.

Sánchez-Bodón Julia J Ruiz-Rubio Leire L Hernáez-Laviña Estíbaliz E Vilas-Vilela José Luis JL Moreno-Benítez Mª Isabel MI

Polymers 20201224 1

In the last few decades, surgical implants have been widely used to restore the function of damaged bones or joints. However, it is essential to receive antibiotic or anti-inflammatory treatment to circumvent significant problems associated, such as the colonization of the implanted surface by bacteria or other microorganisms and strong host inflammatory responses. This article presents the effectiveness of the copper catalyzed alkyne-azide cycloaddition (CuAAC) ("click") reaction by the linkage ...[more]

PMID: 33374150

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Project description:Atherosclerosis involves an ongoing inflammatory response of the vascular endothelium and vessel wall of the aorta and vein. The pleiotropic effects of statins have been well described in many in vitro and in vivo studies, but these effects are difficult to achieve in clinical practice due to the low bioavailability of statins and their first-pass metabolism in the liver. The aim of this study was to test a vessel wall local drug delivery system (DDS) using PLA microstructures loaded with simvastatin. Wistar rats were fed high cholesterol chow as a model. The rat vessels were chemically injured by repeated injections of perivascular paclitaxel and 5-fluorouracil. The vessels were then cultured and treated by the injection of several concentrations of poly(L,L-lactide) microparticles loaded with the high local HMG-CoA inhibitor simvastatin (0.58 mg/kg) concentration (SVPLA). Histopathological examinations of the harvested vessels and vital organs after 24 h, 7 days and 4 weeks were performed. Microcirculation in mice as an additional test was performed to demonstrate the safety of this approach. A single dose of SVPLA microspheres with an average diameter of 6.4 μm and a drug concentration equal to 8.1% of particles limited the inflammatory reaction of the endothelium and vessel wall and had no influence on microcirculation in vivo or in vitro. A potent pleiotropic (anti-inflammatory) effect of simvastatin after local SVPLA administration was observed. Moreover, significant concentrations of free simvastatin were observed in the vessel wall (compared to the maximum serum level). In addition, it appeared that simvastatin, once locally administered as SVPLA particles, exerted potent pleiotropic effects on chemically injured vessels and presented anti-inflammatory action. Presumably, this effect was due to the high local concentrations of simvastatin. No local or systemic side effects were observed. This approach could be useful for local simvastatin DDSs when high, local drug concentrations are difficult to obtain, or systemic side effects are present.

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.

Dataset Information

Poly(l-lactide)-Based Anti-Inflammatory Responsive Surfaces for Surgical Implants.

Publications

Poly(l-lactide)-Based Anti-Inflammatory Responsive Surfaces for Surgical Implants.

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