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1.
Nazely Diban Suvi Haimi Lydia Bolhuis-Versteeg Sandra Teixeira Susanna Miettinen André Poot Dirk Grijpma Dimitrios Stamatialis 《Acta biomaterialia》2013,9(5):6450-6458
At present the manufacture of small-diameter blood vessels is one of the main challenges in the field of vascular tissue engineering. Currently available vascular grafts rapidly fail due to development of intimal hyperplasia and thrombus formation. Poly(lactic-co-glycolic acid) (PLGA) hollow fiber (HF) membranes have previously been proposed for this application, but as we show in the present work, they have an inhibiting effect on cell proliferation and rather poor mechanical properties. To overcome this we prepared HF membranes via phase inversion using blends of PLGA with poly(ε-caprolactone) (PCL). The influence of polymer composition on the HF physicochemical properties (topography, water transport and mechanical properties) and cell attachment and proliferation were studied. Our results show that only the ratio PCL/PLGA of 85/15 (PCL/PLGA85/15) yielded a miscible blend after processing. A higher PLGA concentration in the blend led to immiscible PCL/PLGA phase-separated HFs with an inhomogeneous morphology and variation in the cell culture results. In fact, the PCL/PLGA85/15 blend, which had the most homogeneous morphology and suitable pore structure, showed better human adipose stem cell (hASC) attachment and proliferation compared with the homopolymers. This, combined with the good mechanical and transport properties, makes them potentially useful for the development of small-caliber vascular grafts. 相似文献
2.
Nerve guide scaffolds from block polyurethanes without any additional growth factors or protein were prepared using a particle leaching method. The scaffolds of block polyurethanes (abbreviated as PUCL-ran-EG) based on poly(?-caprolactone) (PCL-diol) and poly(ethylene glycol) (PEG) possess highly surface-area porous for cell attachment, and can provide biochemical and topographic cues to enhance tissue regeneration. The nerve guide scaffolds have pore size 1–5 μm and porosity 88%. Mechanical tests showed that the polyurethane nerve guide scaffolds have maximum loads of 4.98 ± 0.35 N and maximum stresses of 6.372 ± 0.5 MPa. The histocompatibility efficacy of these nerve guide scaffolds was tested in a rat model for peripheral nerve injury treatment. Four types of guides including PUCL-ran-EG scaffolds, autograft, PCL scaffolds and silicone tubes were compared in the rat model. After 14 weeks, bridging of a 10 mm defect gap by the regenerated nerve was observed in all rats. The nerve regeneration was systematically characterized by sciatic function index (SFI), histological assessment including HE staining, immunohistochemistry, ammonia silver staining, Masson's trichrome staining and TEM observation. Results revealed that polyurethane nerve guide scaffolds exhibit much better regeneration behavior than PCL, silicone tube groups and comparable to autograft. Electrophysiological recovery was also seen in 36%, 76%, and 87% of rats in the PCL, PUCL-ran-EG, and autograft groups respectively, whilst 29.8% was observed in the silicone tube groups. Biodegradation in vitro and in vivo show proper degradation of the PUCL-ran-EG nerve guide scaffolds. This study has demonstrated that without further modification, plain PUCL-ran-EG nerve guide scaffolds can help peripheral nerve regeneration excellently. 相似文献
3.
Lei Yao Qingxiang Song Wenkun Bai Jizhen Zhang Deyu Miao Mengyin Jiang Yu Wang Zhiyong Shen Quanyin Hu Xiao Gu Meng Huang Gang Zheng Xiaoling Gao Bing Hu Jun Chen Hongzhuan Chen 《Biomaterials》2014
Nanotechnology plays a unique instrumental role in the revolutionary development of brain-specific drug delivery, imaging, and diagnosis, but is highly limited by the existence of blood–brain barrier (BBB). In this study, microbubble-enhanced unfocused ultrasound (MEUUS) was developed as an approach to mediate an extensive brain delivery of poly (ethylene glycol) – poly (lactic acid) (PEG–PLA) nanoparticles. Following the MEUUS treatment, the nanoparticles signals were found to penetrate through the vascular walls and distributed deeply into the parenchyma at a significantly higher level (more than 250%) than those of the non-MEUUS treated control. Such effect was reversible and dependent on nanoparticles injection timing, sonication mode and mechanical index. Together with the transmission electron microscopy analysis, the increased brain accumulation of nanoparticles was claimed to be largely mediated by an ultrasound-induced stable cavitation of the microbubble which resulted in mechanical stretching of the vessel wall and consequently induced cellular transcytosis of the nanoparticles. The MEUUS technique was also used to facilitate the brain delivery of PEG–PLA nanoparticles functionalized with amyloid beta-specific antibody 6E10 for enabling the recognition of the hallmarks of Alzheimer's disease that widely distributed in the brain. No erythrocytes extravasation and other visible damages in the brain were detected following the MEUUS treatment. These findings together indicated that unfocused ultrasound with the aid of microbubble could effectively improve the brain delivery of nanoparticles, and this approach might serve as a safe and flexible platform for the potential application of nanoparticles in the diagnosis and therapy of brain diseases. 相似文献
4.
The dimensional stability and rheological properties of a series of comb-like copolymers of N-isopropyl acrylamide (NIPAAm) and methoxy poly(ethylene glycol) methacrylate (mPEGMA), poly(NIPAAm–co-mPEGMA), with varying poly(ethylene glycol) (PEG) graft densities and molecular weights were studied. The thermoresponsive character of the copolymer solutions was investigated by kinetic and equilibrium swelling, as well as by static and dynamic mechanical analysis. Surface response mapping was employed to target particular compositions and concentrations with excellent dimensional stability and a relatively large change in dynamic mechanical properties upon thermoreversible gelation. The mechanical characteristics of the gels depended strongly upon concentration of total polymer and less so upon copolymer ratio. Increased PEG graft density was shown to slow the deswelling rate and increase the equilibrium water content of the gels. Upon gelation at sol concentrations of 1–20 wt.% the materials underwent no deswelling or syneresis and maintained stable gels with a large elastic regime and high yield strain (i.e. elastic and soft but tough), even within the Pascal range of complex shear moduli. These materials are unique in that they maintained a physiologically useful lower critical solution temperature (~33 °C), despite having a high PEG content. Copolymers with a high PEG content and low polymer fraction were conveniently transparent in the gel phase, allowing visualization of cellular activity without disrupting the microenvironment. Mesenchymal stem cells showed good viability and proliferation in three-dimensional culture within the gels, despite the lack of ligand incorporation to promote cellular interaction. Multi-component matrices can be created through simple mixing of copolymer solutions and peptide-conjugated linear polymers and proteins to produce combinatorial microenvironments with the potential for use in cell biology, tissue engineering and medical applications. 相似文献
5.
Biomaterials coated polymer/DNA complexes are developed as an efficient non-viral gene delivery system. It is able to circumvent the changes of various biophysical properties of the biomaterials and the corresponding polymer/DNA nanoparticles with covalent linkage. In the present study, we introduced pH-sensitive carboxymethyl poly (l-histidine) (CM-PLH) and poly (β-amino ester) (PbAE) as functional biomaterials to form CM-PLH/PbAE/DNA core-shell ternary complexes system based on electrostatically adsorbed coatings for gene efficient delivery and transfection. The preparation of the complexes was performed self-assembly in 25 mm sodium acetate buffer solution at pH 5.2. The complexes kept stable nano-size, behaving good condensation capacity and low toxicity, even provided a higher transfection efficiency than the binary complexes (PbAE/DNA without CM-PLH) and transfected up to (89.6 ± 4.45) % in HEK293 and (57.1 ± 2.10) % in B16-F10 in vitro. The ternary complexes significantly enhanced their cellular uptake and endosomal escape which were proved by the results that the complexes could evade the endosomal lumen and localize in the nucleus of treated cells visualized under Fluorescence Confocal Microscopy (FCM). The aforementioned results indicated that CM-PLH with pH-sensitive imidazole groups played an important role in enhancing the endosomal escape and transfection efficiency. The in vivo gene transfection confirmed that the ternary complexes with pGL3-promoter as led to effectively deposit at the tumor site by the EPR effect and shown 4 fold higher luciferase expression in B16-F10 tumor than the binary complexes. Consequently, CM-PLH/PbAE/DNA ternary complexes system exhibited significant improvements in transfection efficiency in comparison with non-coated PbAE/DNA both in vitro and in vivo, highlighting their functional prospect. Our approach and the gene delivery system fabrication could potentially be useful for effective gene delivery and therapies to targeted cells. 相似文献
6.
Shahriar Sharifi Sebastien B.G. Blanquer Theo G. van Kooten Dirk W. Grijpma 《Acta biomaterialia》2012,8(12):4233-4243
Soft hydrogels with elasticity modulus values lower than 100 kPa that are tough and biodegradable are of great interest in medicine and in tissue engineering applications. We have developed a series of soft hydrogel structures from different methacrylate-functionalized triblock copolymers of poly(ethylene glycol) (PEG) with poly(trimethylene carbonate) (PTMC) by photo-crosslinking aqueous solutions of the macromonomers in 2.5 and 5 wt.% colloidal dispersions of clay nanoparticles (Laponite XLG). The length of the PTMC blocks of the macromonomers and the clay content determined the physicomechanical properties of the obtained hydrogels. While an increase in the PTMC block length in the macromonomers from 0.2 to 5 kg/mol resulted in a decrease in the gel content, the addition of 5 wt.% Laponite nanoclay to the crosslinking solution lead to very high gel contents of the hydrogels of more than 95%. The effect of PTMC block length on the mechanical properties of the hydrogels was not as pronounced, and soft gels with a compressive modulus of less than 15 kPa and toughness values of 25 kJ m?3 were obtained. However, the addition of 5 wt.% Laponite nanoclay to the formulations considerably increased the compressive modulus and resilience of the hydrogels; swollen nanocomposite networks with compressive modulus and toughness values of up to 67 kPa and 200 kJ m?3, respectively, could then be obtained. The prepared hydrogels were shown to be enzymatically degradable by cholesterol esterase and by the action of macrophages. With an increase in PTMC block length in the hydrogels, the rates of mass loss increased, while the incorporated Laponite nanoclay suppressed degradation. Nanocomposite hydrogel structures with a designed gyroid pore network architecture were prepared by stereolithography. Furthermore, in the swollen state the porous gyroid structures were mechanically stable and the pore network remained fully open and interconnected. 相似文献
7.
《Journal of biomaterials science. Polymer edition》2013,24(3):373-386
Photo-cross-linked poly(vinyl pyrrolidone) (PVP) and poly(ethylene oxide)(PEO)/PVP electrospun nanofibrous mats containing complex-bound iodine have been studied. FT-IR spectroscopy analyses have proved that coordination of molecular iodine with carbonyl group and nitrogen atom of pyrrolidone rings of the PVP chains has taken place. The distribution of iodine along the fibers is uniform as revealed by X-ray mapping. The microbiological tests have demonstrated that the iodine complex-containing electrospun mats are highly effective against the Gram-positive bacterium Staphylococcus aureus, the Gram-negative bacterium Escherichia coli and the fungus Candida albicans. Comparison with iodine complex-containing films has shown that the iodine complex-containing nanofibers exhibit a higher killing rate than the films against bacteria E. coli. SEM observations showed that PVP–iodine nanofibrous mats inhibit the adhesion of bacteria S. aureus. These characteristic features make the electrospun iodine-containing nanofibers good candidates for wound-dressing materials. 相似文献
8.
C Del Gaudio L Fioravanzo M Folin F Marchi E Ercolani A Bianco 《Journal of biomedical materials research. Part B, Applied biomaterials》2012,(7):1883-1898
Tissue engineering can effectively contribute to the development of novel vascular prostheses aimed to overcome the well-known drawbacks of small-diameter grafts. To date, poly(ε-caprolactone) (PCL), a bioresorbable synthetic poly(α-hydroxyester), is considered one of the most promising materials for vascular tissue engineering. In this work, the potential advantage of intimate blending soft PCL and hard poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), a polymer of microbial origin, has been evaluated. Nonwoven mats and small-diameter tubular scaffolds of PCL, PHBV, and PCL/PHBV were fabricated by means of electrospinning technique. Mechanical properties and suture retention strength were investigated according to the international standard for cardiovascular implants. Biological tests demonstrated that both PCL-based scaffolds supported survival and growth of rat cerebral endothelial cells in a short time. The fiber alignment of the electrospun tubular scaffolds contributed to a more rapid and homogeneous cell colonization of the luminal surface. ? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012. 相似文献
9.
《Journal of biomaterials science. Polymer edition》2013,24(8):777-802
A biodegradable polymer network hydrogel with both hydrophobic and hydrophilic components was synthesized and characterized. The hydrophobic and hydrophilic components were a three-arm poly(ε-caprolactone) maleic acid (PGCL-Ma, as the hydrophobic constituent) and poly(ethylene glycol) diacrylate macromer (PEGDA, as a hydrophilic constituent), respectively. These two polymers were chemically photo-crosslinked to generate a three-dimensional network structure, which were characterized by FT-IR, DSC and SEM. The swelling property of the networks was studied in phosphate-buffered saline (PBS, pH 7.4). The results of this study showed that a wide-range swelling property was obtained by changing the composition ratio of PGCL-Ma to PEGDA. The in vitro release of bovine serum albumin (BSA) from these hydrogels as a function of the PEGDA to PGCL-Ma composition ratio and incubation time was examined and we found that the incorporation of PEGDA into PGCL-Ma increased the initial burst release of BSA. As the PEGDA component increased, the rate of formation of a loose three-dimensional (3D) network structure increased; consequently, the sustained rate and extent of BSA release increased. We suggest that the release of BSA was controlled by both diffusion of BSA through swelling of the hydrophilic phase during an early stage and degradation of the hydrophobic phase during a late stage; and that the relative magnitude of diffusion versus degradation controlled release depended on composition ratio and immersion time. 相似文献
10.
Chung AS Hwang HS Das D Zuk P McAllister DR Wu BM 《Journal of biomedical materials research. Part B, Applied biomaterials》2012,100(1):274-284
Electrospun fibrous mats have gained popularity in bioengineering over the past decade, but few papers detail their degradative mechanisms. To address this, blends of hydrophobic poly(ε-caprolactone) (PCL) and hydrophilic PGA-PCL-PGA triblock copolymer were electrospun into aligned fibrous mats to assess the copolymers' mechanical and degradative properties. Increased hydrophilic triblock content led to enhanced morphological uniformity of fiber, tightening of fiber diameters, increased storage and Young's modulus, and decreased elongation. The corresponding decrease in hydrophobic PCL content led to faster hydrolytic degradation rate, as reflected by enhanced decrease in mass, molecular weight, and modulus loss at 25, 37, and 45°C. The activation energy for hydrolytic degradation for 15:85 PCL: triblock copolymer was approximately half that of 85:15 PCL: triblock copolymer. Detailed examination of fiber morphology and crystallinity revealed initial surface erosion followed by the evolution of crystalline lamellar stacks and bulk degradation at 37°C. Because of the high surface to volume and short diffusion length scale of the small diameter fibers, surface and bulk degradation may both contribute to the hydrolytic degradative behavior of these electrospun fibrous mats. Electrospun mats' distinct architecture that embodies high specific surface to volume and interfiber porous ultrastructures that lead to their unique degradative behaviors hold much potential for significant impact in the field of tissue engineering and controlled drug delivery. 相似文献
11.
Shida Li Wenxiu Wei Weiping Jia Lechen Zhao Hongmei Xu Feilong Zhou 《Journal of biomaterials science. Polymer edition》2013,24(18):2299-2311
AbstractA copolymeric micelle formulation of itraconazole (ITR-M) was prepared using linear-dendritic monoallyloxy poly (ethylene glycol)-b-poly (ε-caprolactone) (APEG-PCL) as drug carrier materials. DL and EE values of ITR-M were 5.70?±?0.12% and 91.30?±?1.90%, respectively. The micelle formulation enhanced the ITR solubility up to 30.42?μg/mL. In vitro release of ITR from the ITR-M was mainly drug diffusion process followed by the copolymer’s degradation. ITR-M showed similar anti-Candida albicans activity to that of crude ITR although its release of ITR was slow and continuous. The in vivo pharmacokinetic study demonstrated that the ITR-M could improve tissue distribution of ITR. In conclusion, APEG-PCL could be a potential carrier in the development of antifungal drug delivery system. 相似文献
12.
《Acta biomaterialia》2014,10(5):2125-2132
Polymeric scaffolds that are biocompatible and biodegradable are widely used for tissue engineering applications. Scaffolds can be further enhanced by enabling the release of one or more drugs to stimulate regeneration or for the treatment of a specific disease or condition. In this study, poly(lactic-co-glycolic acid) (PLGA) microspheres were mixed with poly(β-amino ester) (PBAE) particles to create novel hybrid scaffolds capable of dual release of drug and growth factor. Fast-degrading PBAE particles loaded with the drug ketoprofen acted as porogens that provided a rapid 12 h release. The PLGA microspheres were loaded with a growth factor, bone morphogenetic protein 2, and fused together around the porogens to create a slow-degrading matrix that provided sustained release lasting 70 days. Drug release was further tailored by varying the amount of porogen added to the scaffold. Bioactivity measurements demonstrated that the scaffold fabrication technique did not damage the drug or protein. The compressive modulus was affected by the amount of porogen added, extending from 50 to 111 MPa for loadings from 60 to 40% PBAE, and after 5 days of degradation, it decreased to 0.6 to 1.1 kPa when the porogen was gone. PLGA containing a quick-degrading porogen can be used to release two drugs while developing a porous microarchitecture for cell ingrowth with in a matrix capable of maintaining a compressive modulus applicable for soft tissue implants. 相似文献
13.
A series of novel triblock copolymers composed of poly(ethylene glycol) (PEG) and poly(ε-caprolactone)-bearing benzyl carboxylate on the α-carbon of ε-caprolatone were synthesized through ring opening polymerization of α-benzyl carboxylate-ε-caprolactone by dihydroxylated PEG. The debenzylation of the synthesized copolymer, i.e., poly(α-benzyl carboxylate-ε-caprolactone)-b-PEG-b-poly(α-benzyl-carboxylate-ε-caprolactone) (PBCL-b-PEG-b-PBCL), in the presence of hydrogen gas using different levels of catalyst, was carried out to achieve copolymers with various degrees of free α-carboxyl to α-benzyl-ε-carboxylate groups on the hydrophobic block. Incomplete reduction of PBCL led to the formation of poly(α-carboxyl-co-benzyl caboxylate-ε-caprolactone) PCBCL in the lateral blocks at 27%, 50% and 75% carboxyl group substitution. The molecular weight and polydispersity of the resultant copolymers were estimated by 1H NMR and MALDI-TOF. Synthesized triblock copolymers formed stable micelles at low concentrations (critical micellar concentrations (CMC) of 0.34–12.5 μg ml−1). Polymers containing carboxyl groups in their structure showed a pH-dependent increase in CMC. As the pH was raised from 4.0 to 9.0, CMC increased from 0.76 to 1.06 μg ml−1, for 27% debenzylated polymer, and from 1.30 to 2.20 μg ml−1, for 50% debenzylated polymers. In contrast, the CMC in polymers without carboxyl group was independent of pH (0.55 μg ml−1). Different changes in micellar size as a function of temperature was observed depending on the degree of debenzylation on the PCBCL block: polymers with 27% degree of debenzylation illustrated a rise in micelle size from ∼38 to 55 nm as the temperature increased above 29 °C, while polymers with 50% debenzylation showed a decrease in micelle size, from ∼52 to 38 nm, with increase in temperature. A similar trend was observed at pH 4.5, 7.0 and 9.0 for polymers containing carboxyl groups on their hydrophobic block. The temperature for the onset of size change and/or the extent of aggregate size change was found to be dependent on the pH of the medium and the polymer concentration. The results point to a potential for the formation of thermo- and pH-responsive micelles from triblock copolymers of PEG and carboxyl substituted caprolactone. The results also imply a potential for the 27% debenzylated PCBCL-b-PEG-b-PCBCL copolymers to form a biodegradable thermoreversible gel with a transition temperature a few degrees below 37 °C. 相似文献
14.
Safranski DL Weiss D Clark JB Caspersen BS Taylor WR Gall K 《Journal of biomedical materials research. Part A》2011,96(2):320-329
Poly(β-amino ester) networks have shown promise as tissue scaffolds. The objective of this work was to examine the effect of changing poly(ethylene glycol) diacrylate concentration on poly(β-amino ester) network properties and to assess the degradable polymers' in vivo response, using magnetic resonance imaging (MRI) and immunohistochemistry. The networks were synthesized from hexanediol diacrylate (HDDA), poly(ethylene glycol) diacrylate (PEGDA), and a primary amine, 3-methoxypropylamine (3-MOPA), with a fixed overall molar ratio of diacrylate to amine. Network properties were verified to insure that the networks possessed equivalent initial properties and structure other than chemistry. The effect of varying PEGDA concentration on water content, mass loss, and modulus was determined, where increasing the concentration of PEGDA increases both water content, mass loss rate, and decreases modulus. We also show that manipulating the network composition at ratios of 0:100, 10:90 and 25:75 (PEGDA:HDDA) does not elicit a major inflammatory response to subcutaneous implantation of the networks in mice. This work provides a foundation for tailoring poly(β-amino ester) networks, based on degradation rate and modulus, as a means to tune the polymer properties for various biomedical applications. 相似文献
15.
You Qiang Yang Bin Zhao Zhen Dong Li Wen Jing Lin Can Yang Zhang Xin Dong Guo Ju Fang Wang Li Juan Zhang 《Acta biomaterialia》2013,9(8):7679-7690
A series of amphiphilic 4- and 6-armed star triblock co-polymers poly(ε-caprolactone)-b-poly(2-(diethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (4/6AS-PCL-b-PDEAEMA-b-PPEGMA) were developed by a combination of ring opening polymerization and continuous activators regenerated by electron transfer atom transfer radical polymerization. The critical micelle concentration values of the star co-polymers in aqueous solution were extremely low (2.2–4.0 mg l–1), depending on the architecture of the co-polymers. The self-assembled blank and doxorubicin (DOX)-loaded three layer micelles were spherical in shape with an average size of 60–220 nm determined by scanning electron microscopy and dynamic light scattering. The in vitro release behavior of DOX from the three layer micelles exhibited pH-dependent properties. The DOX release rate was significantly accelerated by decreasing the pH from 7.4 to 5.0, due to swelling of the micelles at lower pH values caused by the protonation of tertiary amine groups in DEAEMA in the middle layer of the micelles. The in vitro cytotoxicity of DOX-loaded micelles to HepG2 cells suggested that the 4/6AS-PCL-b-PDEAEMA-b-PPEGMA micelles could provide equivalent or even enhanced anticancer activity and bioavailability of DOX and thus a lower dosage is sufficient for the same therapeutic efficacy. The results demonstrate that the pH-sensitive multilayer micelles could have great potential application in delivering hydrophobic anticancer drugs for improved cancer therapy. 相似文献
16.
目的研究Toll样受体3(toll-like receptor 3,TLR3)在poly(I-C)诱发小鼠流产中的潜在作用。方法多聚次黄苷酸-胞苷酸[polyinosinic-polycytidync acid,poly(I-C)]是一种双链RNA,腹腔注射时能够诱发小鼠流产。在预先用单抗阻断或不阻断TLR3情况下,注射poly(I-C)建立小鼠诱发性流产模型,应用流式细胞术分别检测CD45+DX5+和DX5+CD69+细胞百分率。结果不用抗TLR3抗体预处理,单用poly(I-C)刺激同种异基因交配模型BALB/c×C57BL/6,可使CD45+DX5+和DX5+CD69+细胞百分率均显著升高。但是,应用抗TLR3抗体预处理的雌鼠,用poly(I-C)刺激时上述百分率不改变。与此相应,poly(I—C)刺激可显著增高胚胎吸收率,而抗TLR3抗体预处理可消除这种作用。结论poly(I-C)与TLR3结合可能对母-胎界面NK细胞活化至关重要,并可促进小鼠胚胎吸收。 相似文献
17.
Mani Prabaharan Jamison J. Grailer Srikanth Pilla Douglas A. Steeber Shaoqin Gong 《Biomaterials》2009,30(16):3009-3019
Folate-conjugated amphiphilic hyperbranched block copolymer (H40–PLA-b-MPEG/PEG–FA) with a dendritic Boltorn® H40 core, a hydrophobic poly(l-lactide) (PLA) inner shell and a hydrophilic methoxy poly(ethylene glycol) (MPEG) and folate-conjugated poly(ethylene glycol) (PEG–FA) outer shell was synthesized as a carrier for tumor-targeted drug delivery. The block copolymer was characterized using 1H NMR and gel permeation chromatography (GPC) analysis. Due to its core–shell structure, this block polymer forms unimolecular micelles in aqueous solutions. The micellar properties of H40–PLA-b-MPEG/PEG–FA block copolymer were extensively studied by dynamic light scattering (DLS), fluorescence spectroscopy, and transmission electron microscopy (TEM). An anticancer drug, doxorubicin in the free base form (DOX) was encapsulated into H40–PLA-b-MPEG/PEG–FA micelles. The DOX-loaded micelles provided an initial burst release (up to 4 h) followed by a sustained release of the entrapped DOX over a period of about 40 h. Cellular uptake of the DOX-loaded H40–PLA-b-MPEG/PEG–FA micelles was found to be higher than that of the DOX-loaded H40–PLA-b-MPEG micelles because of the folate-receptor-mediated endocytosis, thereby providing higher cytotoxicity against the 4T1 mouse mammary carcinoma cell line. In vitro degradation studies revealed that the H40–PLA-b-MPEG/PEG–FA block copolymer hydrolytically degraded into polymer fragments within six weeks. These results indicated that the micelles prepared from the H40–PLA-b-MPEG/PEG–FA block copolymer have great potential as tumor-targeted drug delivery nanocarriers. 相似文献
18.
In order to evaluate the potential and mechanism of Angiopep-conjugated poly(ethylene glycol)-co-poly(?-caprolactone)nanoparticles (ANG-PEG-NP) as brain targeting drug delivery system, Rhodamine B isothiocyanate (RBITC) was used as a fluorescent probe molecule to label ANG-PEG-NP through covalent bonding. The brain transcytosis across the blood-brain barrier (BBB) and brain delivery in mice of RBITC labeled ANG-PEG-NP were investigated in this paper. Results showed that ANG-PEG-NP enhanced significantly the uptake by BCECs compared with that of PEG-NP through caveolae- and clathrin-mediated endocytosis, involving a time-dependent, concentration-dependent and energy-dependent mode. The transport of ANG-PEG-NP across the in vitro BBB model was significantly increased than that of PEG-NP. After injection a dose of 100 mg/kg RBITC labeled ANG-PEG-NP or PEG-NP in mouse caudal vein, the brain coronal section showed a higher accumulation of ANG-PEG-NP in the cortical layer, lateral ventricle, third ventricles and hippocampus than that of PEG-NP. By using an excess of free LRP ligand (Angiopep-2 and/or Aprotinin) as a specific receptor inhibitor, it was evidenced that the uptake by BCECs in vitro, transport across in vitro BBB model and penetration into brain tissue in vivo of RBITC labeled ANG-PEG-NP could be inhibited significantly, which demonstrated the brain targeting mechanism of Angiopep-conjugated poly(ethylene glycol)-co-poly(?-caprolactone)nanoparticles might be a LRP receptor mediated transcytosis process. Understanding these issues is important for the future development of ANG-PEG-NP as a brain targeting drug delivery system for neurodegenerative disorders including glioma and Alzheimer’s disease. 相似文献
19.
Mun CH Jung Y Kim SH Lee SH Kim HC Kwon IK Kim SH 《Tissue engineering. Part A》2012,18(15-16):1608-1616
Nanofibers have been applied to tissue engineering scaffolds because fiber diameters are of the same scale as the physical structure of protein fibrils in the native extracellular matrix. In this study, we utilized cell matrix engineering combined with cell sheet matrix and electrospinning technologies. We studied small-diameter vascular grafts in vitro by seeding smooth muscle cells onto electrospun poly(lactide-co-?-caprolactone) (PLCL) scaffolds, culturing and constructing a three-dimensional network. The vascular grafts constructed using cell matrix engineering were similar to the native vessels in their mechanical properties, such as tensile strength, tensile strain, and e-modulus. Also, they had a self-sealing property more improved than GORE-TEX because PLCL has compatible elasticity. Small-diameter vascular grafts constructed using matrix engineering have the potential to be suitable for vascular grafts. 相似文献
20.
《Journal of biomaterials science. Polymer edition》2013,24(7):829-841
The effects of temperature on the monolayer behavior of the poly(γ-benzyl L-glutamate) (PBLG)/poly(N-isopropylacrylamide) (PNIPAAm) diblock copolymer at the air-water interface were examined. Differences in the adhesion and morphology of hepatocytes between Langmuir-Blodgett (LB) films and cast surfaces of the PBLG/PNIPAAm diblock copolymer were investigated. The surface pressure (π)-area (A) curve of the block copolymer had a tendency to expand with the temperature, due to a change in the conformation of PNIPAAm with the temperature change. Attachment of hepatocytes onto the PBLG/PNIPAAm block copolymer LB surface decreased slightly with an increase of the PNIPAAm content in the block copolymer, whereas that onto the cast surface decreased rapidly with an increase of the PNIPAAm content, due to the hydrophilic property of PNIPAAm in the microphase-separated structure. Rapid morphological changes of the hepatocytes adhered to the LB surfaces, from round shapes to spreading ones, were observed, compared with the cast films. The hepatocytes that adhered to the block copolymer LB surfaces showed less flattened and spread shapes than those that adhered to the PBLG one. Also, the spheroid formation of the hepatocytes increased with an increase of the PNIPAAm content in the block copolymer cast films. 相似文献