Synthesis and Antiplatelet Adhesion Behavior of a Poly(L-lactide-co-glycolide)–Poly(1,5-dioxepan-2-one) Multiblock Copolymer
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ABSTRACT:
SUBMITTER: Jikei M
PROVIDER: S-EPMC8552321 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In this work, the synthesized PLLA/PCL multi-block copolymers with different compositions were introduced into a stereocomplexed poly(lactide) (sc-PLA) matrix to accelerate the stereocomplexation of PLA enantiomers and improve its inherent brittleness. The PLLA/PCL multi-block copolymers were in different compositions to adjust the molecular weight of the PLLA block. The structure, molecular weight, crystallization behavior, crystal structure and thermal stability of PLLA/PCL multi-block copolymers were investigated. The results indicated that PLLA/PCL multi-block copolymers with controllable structure and composition were successfully synthesized. On this basis, the blends of sc-PLA and PLLA/PCL multi-block copolymers were prepared by solution casting, and characterized. The results revealed that the introduction of PLLA/PCL multi-block copolymers promoted the stereocomplexation of the PLA enantiomers during the melting crystallization process to obtain a complete stereocomplexed material. But the presence of the PCL block leads to a decrease in the melting temperature of the stereocomplex and difficulty in homogeneous nucleation. Compared with sc-PLA, the elongation at break of the blends was significantly improved and their tensile strengths were only slightly reduced. And the thermal stability and mechanical properties of the blends could be adjusted by controlling the content and composition of PCL/PLLA multi-block copolymers. These results revealed that the degree of stereocomplexation and toughness of sc-PLA were improved, which may expand the application fields of PLA-based materials.
| S-EPMC9063687 | biostudies-literature
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.
| S-EPMC4681614 | biostudies-literature
Project description:Vascular endothelial growth factor (VEGF) is the major regulating factor for the formation of new blood vessels, also known as angiogenesis. VEGF is often incorporated in synthetic scaffolds to promote vascularization and to enhance the survival of cells that have been seeded in these devices. Such applications require sustained local delivery of VEGF of around 4 weeks for stable blood vessel formation. Most delivery systems for VEGF only provide short-term release for a couple of days, followed by a release phase with very low VEGF release. We now have developed VEGF-loaded polymeric microspheres that provide sustained release of bioactive VEGF for 4 weeks. Blends of two swellable poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone)-b-poly(l-lactide) ([PCL-PEG-PCL]-b-[PLLA])-based multiblock copolymers with different PEG content and PEG molecular weight were used to prepare the microspheres. Loading of the microspheres was established by a solvent evaporation-based membrane emulsification method. The resulting VEGF-loaded microspheres had average sizes of 40-50 μm and a narrow size distribution. Optimized formulations of a 50:50 blend of the two multiblock copolymers had an average VEGF loading of 0.79 ± 0.09%, representing a high average VEGF loading efficiency of 78 ± 16%. These microspheres released VEGF continuously over 4 weeks in phosphate-buffered saline pH 7.4 at 37 °C. This release profile was preserved after repeated and long-term storage at -20 °C for up to 9 months, thereby demonstrating excellent storage stability. VEGF release was governed by diffusion through the water-filled polymer matrix, depending on PEG molecular weight and PEG content of the polymers. The bioactivity of the released VEGF was retained within the experimental error in the 4-week release window, as demonstrated using a human umbilical vein endothelial cells proliferation assay. Thus, the microspheres prepared in this study are suitable for embedment in polymeric scaffolds with the aim of promoting their functional vascularization.
| S-EPMC6681988 | biostudies-literature
Project description:The synthesis of a family of new poly(lactic acid-co-glycerol monostearate) (PLA-PGC18) copolymers and their use as biodegradable polymer dopants is reported to enhance the hydrophobicity of poly(lactic acid-co-glycolic acid) (PLGA) nonwoven meshes. Solutions of PLGA are doped with PLA-PGC18 and electrospun to form meshes with micrometer-sized fibers. Fiber diameter, percent doping, and copolymer composition influence the nonwetting nature of the meshes and alter their mechanical (tensile) properties. Contact angles as high as 160° are obtained with 30% polymer dopant. Lastly, these meshes are nontoxic, as determined by an NIH/3T3 cell biocompatibility assay, and displayed a minimal foreign body response when implanted in mice. In summary, a general method for constructing biodegradable fibrous meshes with tunable hydrophobicity is described for use in tissue engineering and drug delivery applications.
| S-EPMC4215912 | biostudies-literature
Project description:Polymeric biomaterials have found widespread applications in nanomedicine, and poly(lactide-co-glycolide), (PLGA) in particular has been successfully implemented in numerous drug delivery formulations due to its synthetic malleability and biocompatibility. However, the need for preconception in these formulations is increasing, and this can be achieved by selection and elimination of design variables in order for these systems to be tailored for their specific applications. The starting materials and preparation methods have been shown to influence various parameters of PLGA-based nanocarriers and their implementation in drug delivery systems, while the implementation of computational simulations as a component of formulation studies can provide valuable information on their characteristics. This review provides a critical summary of the synthesis and applications of PLGA-based systems in bio-medicine and outlines experimental and computational design considerations of these systems.
| S-EPMC7026499 | biostudies-literature
Project description:The aim of the study was the evaluation of gamma irradiation and electron beams for sterilization of porous scaffolds with shape memory behavior obtained from biodegradable terpolymers: poly(l-lactide-co-glycolide-co-trimethylene carbonate) and poly(l-lactide-co-glycolide-co-ɛ-caprolactone). The impact of mentioned sterilization techniques on the structure of the scaffolds before and after the sterilization process using irradiation doses ranged from 10 to 25 kGy has been investigated. Treatment of the samples with gamma irradiation at 15 kGy dose resulted in considerable drop in glass transition temperature (Tg) and number average molecular weight (Mn). For comparison, after irradiation of the samples using an electron beam with the same dose, no significant changes in structure or properties of examined scaffolds have been noticed. Higher doses of irradiation via electron beam caused essential changes of the scaffolds' pores resulting in partial melting of their surface. Nevertheless, obtained results have revealed that sterilization with electron beam, when compared to gamma irradiation, is a better method because it does not affect significantly the physicochemical properties of the scaffolds. Both used methods of sterilization did not influence the shape memory behavior of the examined materials.
| S-EPMC5456516 | biostudies-literature
Project description:Novel biocomposites of poly(L-lactide) (PLLA) and poly(l-lactide-co-glycolide) (PLLGA) with 10 wt.% of surface-modified hydroxyapatite particles, designed for applications in bone tissue engineering, are presented in this paper. The surface of hydroxyapatite (HAP) was modified with polyethylene glycol by using l-lysine as a linker molecule. The modification strategy fulfilled two important goals: improvement of the adhesion between the HAP surface and PLLA and PLLGA matrices, and enhancement of the osteological bioactivity of the composites. The surface modifications of HAP were confirmed by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), TGA, and elemental composition analysis. The influence of hydroxyapatite surface functionalization on the thermal and in vitro biological properties of PLLA- and PLLGA-based composites was investigated. Due to HAP modification with polyethylene glycol, the glass transition temperature of PLLA was reduced by about 24.5 °C, and melt and cold crystallization abilities were significantly improved. These achievements were scored based on respective shifting of onset of melt and cold crystallization temperatures and 1.6 times higher melt crystallization enthalpy compared with neat PLLA. The results showed that the surface-modified HAP particles were multifunctional and can act as nucleating agents, plasticizers, and bioactive moieties. Moreover, due to the presented surface modification of HAP, the crystallinity degree of PLLA and PLLGA and the polymorphic form of PLLA, the most important factors affecting mechanical properties and degradation behaviors, can be controlled.
| S-EPMC7556045 | biostudies-literature
Project description:To design, fabricate, characterize, and in vivo assay clinically viable magnetic particles for MRI-based cell tracking.Poly(lactide-co-glycolide) (PLGA) encapsulated magnetic nano and microparticles were fabricated. Multiple biologically relevant experiments were performed to assess cell viability, cellular performance, and stem cell differentiation. In vivo MRI experiments were performed to separately test cell transplantation and cell migration paradigms, as well as in vivo biodegradation.Highly magnetic nano (?100 nm) and microparticles (?1-2 µm) were fabricated. Magnetic cell labeling in culture occurred rapidly achieving 3-50 pg Fe/cell at 3 h for different particles types, and >100 pg Fe/cell after 10 h, without the requirement of a transfection agent, and with no effect on cell viability. The capability of magnetically labeled mesenchymal or neural stem cells to differentiate down multiple lineages, or for magnetically labeled immune cells to release cytokines following stimulation, was uncompromised. An in vivo biodegradation study revealed that NPs degraded ?80% over the course of 12 weeks. MRI detected as few as 10 magnetically labeled cells, transplanted into the brains of rats. Also, these particles enabled the in vivo monitoring of endogenous neural progenitor cell migration in rat brains over 2 weeks.The robust MRI properties and benign safety profile of these particles make them promising candidates for clinical translation for MRI-based cell tracking.
| S-EPMC4336220 | biostudies-literature
Project description:The efficient delivery of chemotherapeutics to the tumor via nanoparticle (NP)-based delivery systems remains a significant challenge. This is compounded by the fact that the tumor is highly dynamic and complex environment composed of a plurality of cell types and extracellular matrix. Since glycosaminoglycan (GAG) production is altered in many diseases (or pathologies), NPs bearing GAG moieties on the surface may confer some unique advantages in interrogating the tumor microenvironment. In order to explore this premise, in the study reported here poly-lactide-co-glycolide (PLGA) NPs in the range of 100-150 nm bearing various proteoglycans were synthesized by a single-step nanoprecipitation and characterized. The surface functionalization of the NPs with GAG moieties was verified using zeta potential measurements and X-ray photoelectron spectroscopy. To establish these GAG-bearing NPs as carriers of therapeutics, cellular toxicity assays were undertaken in lung epithelial adenocarcinoma (A549) cells, human pulmonary microvascular endothelial cells (HPMEC), and renal proximal tubular epithelial cells. In general NPs were well tolerated over a wide concentration range (100-600 μg/mL) by all cell types and were taken up to appreciable extents without any adverse cell response in A549 cells and HPMEC. Further, GAG-functionalized PLGA NPs were taken up to different extents in A459 cells and HPMEC. In both cell systems, the uptake of heparin-modified NPs was diminished by 50%-65% in comparison to that of unmodified PLGA. Interestingly, the uptake of chondroitin sulfate NPs was the highest in both cell systems with 40%-60% higher uptake when compared with that of PLGA, and this represented an almost twofold difference over heparin-modified NPs. These findings suggest that GAG modification can be explored as means of changing the uptake behavior of PLGA NPs and these NP systems have potential in cancer therapy.
| S-EPMC4304601 | biostudies-literature
Project description:Monitoring the location, distribution and long-term engraftment of administered cells is critical for demonstrating the success of a cell therapy. Among available imaging-based cell tracking tools, magnetic resonance imaging (MRI) is advantageous due to its noninvasiveness, deep penetration, and high spatial resolution. While tracking cells in preclinical models via internalized MRI contrast agents (iron oxide nanoparticles, IO-NPs) is a widely used method, IO-NPs suffer from low iron content per particle, low uptake in nonphagocytotic cell types (e.g., mesenchymal stem cells, MSCs), weak negative contrast, and decreased MRI signal due to cell proliferation and cellular exocytosis. Herein, we demonstrate that internalization of IO-NP (10 nm) loaded biodegradable poly(lactide-co-glycolide) microparticles (IO/PLGA-MPs, 0.4-3 ?m) in MSCs enhances MR parameters such as the r(2) relaxivity (5-fold), residence time inside the cells (3-fold) and R(2) signal (2-fold) compared to IO-NPs alone. Intriguingly, in vitro and in vivo experiments demonstrate that internalization of IO/PLGA-MPs in MSCs does not compromise inherent cell properties such as viability, proliferation, migration and their ability to home to sites of inflammation.
| S-EPMC3552518 | biostudies-literature