Hollow fibers of poly(lactide-co-glycolide) and poly(ε-caprolactone) blends for vascular tissue engineering applications

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.     

Antibacterial and antimycotic activity of a cross-linked electrospun poly(vinyl pyrrolidone)–iodine complex and a poly(ethylene oxide)/poly(vinyl pyrrolidone)–iodine complex

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.     

Facilitated brain delivery of poly (ethylene glycol)–poly (lactic acid) nanoparticles by microbubble-enhanced unfocused ultrasound

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.     

Mechanical and swelling characterization of poly(N-isopropyl acrylamide -co- methoxy poly(ethylene glycol) methacrylate) sol–gels

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.     

Biodegradable nanocomposite hydrogel structures with enhanced mechanical properties prepared by photo-crosslinking solutions of poly(trimethylene carbonate)–poly(ethylene glycol)–poly(trimethylene carbonate) macromonomers and nanoclay particles

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.     

Electrospun tubular scaffolds: On the effectiveness of blending poly(ε-caprolactone) with poly(3-hydroxybutyrate-co-3-hydroxyvalerate)

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.     

Scaffolds from block polyurethanes based on poly(ɛ-caprolactone) (PCL) and poly(ethylene glycol) (PEG) for peripheral nerve regeneration

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.     

Synthesis,characterization and drug release from three-arm poly(ε-caprolactone) maleic acid/poly(ethylene glycol) diacrylate hydrogels

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.     

Lamellar stack formation and degradative behaviors of hydrolytically degraded poly(ε-caprolactone) and poly(glycolide-ε-caprolactone) blended fibers

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.     

Mechanical properties and dual drug delivery application of poly(lactic-co-glycolic acid) scaffolds fabricated with a poly(β-amino ester) porogen

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.     

Characterization of the thermo- and pH-responsive assembly of triblock copolymers based on poly(ethylene glycol) and functionalized poly(ε-caprolactone)

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.     

Effect of poly(ethylene glycol) diacrylate concentration on network properties and in vivo response of poly(β-amino ester) networks

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.     

Characterization of electrospun core/shell poly(vinyl pyrrolidone)/poly(L-lactide-co-ε-caprolactone) fibrous membranes and their cytocompatibility in vitro

Coaxial electrospinning is a new technique to fabricate continuous composite ultrafine fibers with core/shell structure, which has a broad application perspective in the biomedical field. In this study, ultrafine fibrous membranes of core/shell poly(vinyl pyrrolidone)/poly(L-lactide-co-ε-caprolactone) (PVP/PLCL) were produced by coaxial electrospinning and the structural morphology of the obtained ultrafine fibers was observed by scanning electron microscopy and transmission electron microscopy. Electrospun PLCL and chitosan membranes were also prepared by traditional electrospinning as controls. The electrospun PVP/PLCL membranes showed the largest water absorption (501.3%) in phosphate buffer solution due to introduction of the PVP component and the core/shell fiber structure. Results of tensile tests indicated that the electrospun PVP/PLCL membranes possessed higher tensile strength and elongation-at-break, and lower Young's modulus than those of PLCL and chitosan membranes in both dry and wet states. Studies on cell adhesion, viability and morphology on the fibrous membranes showed that PVP/PLCL membranes could mimic the structure of natural extracellular matrices and positively promote cell–cell and cell–matrix interactions because of hydrophilicity/hydrophobicity balance.     

Improved small molecule drug release from in situ forming poly(lactic-co-glycolic acid) scaffolds incorporating poly(β-amino ester) and hydroxyapatite microparticles

In situ forming implants are an attractive choice for controlled drug release into a fixed location. Currently, rapidly solidifying solvent exchange systems suffer from a high initial burst, and sustained release behavior is tied to polymer precipitation and degradation rate. The present studies investigated addition of hydroxyapatite (HA) and drug-loaded poly(β-amino ester) (PBAE) microparticles to in situ forming poly(lactic-co-glycolic acid) (PLGA)-based systems to prolong release and reduce burst. PBAEs were synthesized, imbibed with simvastatin (osteogenic) or clodronate (anti-resorptive), and then ground into microparticles. Microparticles were mixed with or without HA into a PLGA solution, and the mixture was injected into buffer, leading to precipitation and creating solid scaffolds with embedded HA and PBAE microparticles. Simvastatin release was prolonged through 30?days, and burst release was reduced from 81 to 39% when loaded into PBAE microparticles. Clodronate burst was reduced from 49 to 32% after addition of HA filler, but release kinetics were unaffected after loading into PBAE microparticles. Scaffold dry mass remained unchanged through day 15, with a pronounced increase in degradation rate after day 30, while wet scaffolds experienced a mass increase through day 25 due to swelling. Porosity and pore size changed throughout degradation, likely due to a combination of swelling and degradation. The system offers improved release kinetics, multiple release profiles, and rapid solidification compared to traditional in situ forming implants.     

TLR3参与poly(I-C)所致流产的作用

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。     

Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn® H40, poly(l-lactide) and poly(ethylene glycol) for tumor-targeted drug delivery

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.     

Itraconazole-loaded micelles based on linear-dendritic poly (ethylene glycol)-b-poly (ε-caprolactone)

Abstract

A 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.     

Three-dimensional electrospun poly(lactide-co-ɛ-caprolactone) for small-diameter vascular grafts

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.     

New magnetic-resonance-imaging-visible poly(ε-caprolactone)-based polyester for biomedical applications

A great deal of effort has been made since the 1990s to enlarge the field of magnetic resonance imaging. Better tissue contrast, more biocompatible contrast agents and the absence of any radiation for the patient are some of the many advantages of using magnetic resonance imaging (MRI) rather than X-ray technology. But implantable medical devices cannot be visualized by conventional MRI and a tool therefore needs to be developed to rectify this. The synthesis of a new MRI-visible degradable polymer is described by grafting an MR contrast agent (DTPA-Gd) to a non-water-soluble, biocompatible and degradable poly(ε-caprolactone) (PCL). The substitution degree, calculated by (1)H nuclear magnetic resonance and inductively coupled plasma-mass spectrometry, is close to 0.5% and proves to be sufficient to provide a strong and clear T1 contrast enhancement. This new MRI-visible polymer was coated onto a commercial mesh for tissue reinforcement using an airbrush system and enabled in vitro MR visualization of the mesh for at least 1 year. A stability study of the DTPA-Gd-PCL chelate in phosphate-buffered saline showed that a very low amount of gadolinium was released into the medium over 52 weeks, guaranteeing the safety of the device. This study shows that this new MRI-visible polymer has great potential for the MR visualization of implantable medical devices and therefore the post-operative management of patients.     

(−)−Hinokinin-loaded poly(d,l-lactide-co-glycolide) microparticles for Chagas disease

The (?)?hinokinin display high activity against Trypanosoma cruzi in vitro and in vivo. (?)?Hinokinin-loaded poly(d,l-lactide-co-glycolide) microparticles were prepared and characterized in order to protect (?)?hinokinin of biological interactions and promote its sustained release for treatment of Chagas disease. The microparticles contain (?)?hinokinin were prepared by the classical method of the emulsion/solvent evaporation. The scanning electron microscopy, light-scattering analyzer were used to study the morphology and particle size, respectively. The encapsulation efficiency was determined, drug release studies were kinetically evaluated, and the trypanocidal effect was evaluated in vivo. (?)?Hinokinin-loaded microparticles obtained showed a mean diameter of 0.862?µm with smooth surface and spherical shape. The encapsulation efficiency was 72.46?±?2.92% and developed system maintained drug release with Higuchi kinetics. The preparation method showed to be suitable, since the morphological characteristics, encapsulation efficiency, and in vitro release profile were satisfactory. In vivo assays showed significant reduction of mice parasitaemia after administration of (?)?hinokinin-loaded microparticles. Thus, the developed microparticles seem to be a promising system for sustained release of (?)?hinokinin for treatment of Chagas disease.