Polycaprolactone Block Copolymer Research Articles

Tuning the properties of polycaprolactone-based fibers by using polyethylene oxide / polycaprolactone block copolymers

Tuning the properties of polycaprolactone-based fibers by using polyethylene oxide / polycaprolactone block copolymers

Polycaprolactone scaffolds prepared by 3D printing electrosprayed with polyethylene glycol-polycaprolactone block copolymers for applications in bone tissue engineering

Additive manufacturing technologies and their ability to produce customized items have gained interest in different fields, such as in the design of personalized scaffolds for tissue engineering applications. Although different materials and printers are available in the market, fused filament 3D printers are common and accessible to any user, and, in addition, some commercially available filaments are potentially biocompatible. In this sense, polycaprolactone (PCL) stands out for bone tissue engineering owing to its biocompatibility and appropriate thermal and mechanical properties. In this work, we present the designing, printing, and characterization of 3D porous scaffolds obtained using a free software for 3D printing, a commercial 3D printer, and PCL filament. The printed scaffolds presented adequate porosity (60 %), with pores of around 500 μm, and mechanical properties (compressive modulus of 91 MPa) to be used in bone tissue engineering, low wettability, and a smooth, regular surface. As these two last characteristics may jeopardize an adequate cellular response towards the adhesion and mineralization of the scaffolds, the 3D printed PCL objects were submitted to electrospraying with different poly(ethylene glycol)/PCL block copolymers (PEGm-b-PCLn), showing different hydrophobic/hydrophilic balance, resulting in a rough layer covering the surface of the printed scaffolds. This layer preserves the macrostructure and mechanical characteristics of the scaffolds and allows tuning material surface roughness and hydrophilia. All PCL3D scaffolds allowed osteogenic induction, and the coated scaffolds, showing a rough surface, allowed calcium deposition at day 14.

Caffeic Acid Modified Nanomicelles Inhibit Articular Cartilage Deterioration and Reduce Disease Severity in Experimental Inflammatory Arthritis.

Inflammation plays an important role in the development of rheumatoid arthritis (RA). NR4A1 is an anti-inflammatory orphan nuclear receptor involved in protection from inflammatory stimuli in RA. In this study we have explored the anti-inflammatory potential of the FDA-approved drug 9-aminoacridine (9AA) and the natural compound caffeic acid (CA) conjugated to nanomicelles for the treatment of RA. We have synthesized methoxy polyethylene glycol polycaprolactone block copolymer (mPEG-b-PCL) by ring opening polymerization of ε-caprolactone. Then, we conjugated the hydrophilic caffeic acid (CA) with mPEG-b-PCL micelles via Steglich esterification and incorporated the 9AA drug. These nanomicelles were formulated by the solvent evaporation method with a size distribution around 190 nm and showed maximum drug loading capacity along with sustained drug release behavior. Furthermore, we tested the therapeutic potential of the formulated 9AA-encapsulated CA-conjugated nanomicelles (9AA-NMs) against an experimental RA model. We observed promising results which showed alleviation of arthritic symptoms by reducing inflammation, joint damage, bone erosion, and swelling. Further, collagen destruction was significantly reduced in articular cartilage, as shown by safranin-O and toluidine blue staining. The protective mechanism might be due to the simultaneous inhibition of NF-κB by 9AA and CA, whereas the activation of NR4A1 by 9AA leads to the suppression of HIF-1α. This combined therapeutic effect of 9AA and CA has enhanced the therapeutic efficacy of 9AA-NM and markedly reduced the severity of inflammatory arthritis. Unlike existing drugs for pain management and with limited efficacy, 9AA-NM exerted a disease-relevant activation/blockade that alleviated inflammation and exhibited marked therapeutic efficacy against RA.

Precise fabrication of folic acid-targeted therapy on metformin encapsulated β-cyclodextrin nanomaterials for treatment and care of lung cancer

The potential of metformin to protect against cancer has attracted considerable attention. This investigation aimed to evaluate the evidence for metformin in patients with lung cancer and type 2 diabetes. Metformin drug-loading capacity, biosafety, and bioavailability were improved using a novel drug delivery system for folate receptor-targeted β-cyclodextrin (β-CD). By incorporating folic acid (FA) into nanomaterials (NMs), controlled release and targeted distribution were established. Fabrication of β-CD polycaprolactone block copolymers conjugated with folic acid was used to construct nanomaterials loaded with metformin (FA-Met-NMs). The capacity of the nanomaterials to target tumors was investigated in terms of their physicochemical characteristics and stability. FA-Met-NMs had an average particle size of ~150 nm and a drug loading capacity of ~21%. In addition, FA-Met-NMs showed excellent stability for 72 h in vitro. Metformin release profiles of FA-Met-NMs was considerably quicker at pH 6.4% than at pH 7.4%, suggesting that metformin can be concentrated at the lung tumor site relative to non-cancerous cells. Furthermore, the cellular internalization of FA-Met-NMs was assisted by endocytosis via FA receptors, and their toxic effects were directly proportional to cellular uptake. The morphology of lung cancer cells was examined using various biochemical staining assays, such as calcein-AM and PI analysis. These in vivo experiments verified that FA-Met-NMs accumulated at A549 lung tumor sites and had significant antitumor efficacy with low toxicity. Owing to their active targeting and controlled release, FA-Met-NMs appear to be a viable method for improving cancer treatment. These results suggest that FA-Met-NMs are a promising method for enhancing lung cancer treatment via controllable release and active targeting.

Antibiotic-Loaded Polymersomes for Clearance of Intracellular Burkholderia thailandensis.

Melioidosis caused by the facultative intracellular pathogen Burkholderia pseudomallei is difficult to treat due to poor intracellular bioavailability of antibiotics and antibiotic resistance. In the absence of novel compounds, polymersome (PM) encapsulation may increase the efficacy of existing antibiotics and reduce antibiotic resistance by promoting targeted, infection-specific intracellular uptake. In this study, we developed PMs composed of widely available poly(ethylene oxide)-polycaprolactone block copolymers and demonstrated their delivery to intracellular B. thailandensis infection using multispectral imaging flow cytometry (IFC) and coherent anti-Stokes Raman scattering microscopy. Antibiotics were tightly sequestered in PMs and did not inhibit the growth of free-living B. thailandensis. However, on uptake of antibiotic-loaded PMs by infected macrophages, IFC demonstrated PM colocalization with intracellular B. thailandensis and a significant inhibition of their growth. We conclude that PMs are a viable approach for the targeted antibiotic treatment of persistent intracellular Burkholderia infection.

Perylene-Tagged Polycaprolactone Block Copolymers and Their Enzyme-Biodegradable Fluorescent Nanoassemblies for Intracellular Bio-imaging in Cancer Cells

The present investigation reports enzyme-biodegradable perylenebisimide (PBI)-tagged polycaprolactone (PCL) block copolymers, and their aqueous nanoassemblies were employed as probes for intracellular bio-imaging in cancer cells. Bishydroxyl functionalized PBI initiator was tailor-made, and it was employed as initiator for the ring opening polymerization (ROP) methodology to make PBI-tagged tert-butyl ester-substituted polycaprolactone (PBI-BPCLx) block copolymers. The deprotection of these copolymers yielded carboxylic acid-substituted PBI-CPCLx amphiphilic block copolymers. The carboxylic blocks were self-assembled to produce stable red-fluorescent nanoparticles of <150 nm in size in aqueous medium with fluorescent quantum yield of ϕ = 0.25–0.30 suitable for bio-imaging application. In vitro studies confirmed that the aliphatic polyester backbone in the PBI-CPCLx polymer nanoparticles was readily biodegradable by lysosomal enzymes under physiological conditions. Dynamic light scattering, gel permeation ...

Hierarchical structure microspheres of PCL block copolymers via electrospraying as coatings for fabric with mechanical durability and self‐cleaning ability

The various morphology and structure microspheres were fabricated via one‐step single‐solvent electrospraying of hydrophilic and hydrophobic block modified copolymer of polycaprolactone (PCL). A honeycomb‐like hierarchical structure microspheres of PCL‐b‐PTFOA(4h) and abundant nanometer pores of PCL‐b‐PEG400 microspheres were obtained due to the solvent evaporation, thermally and polymer diffusion‐induced phase separation effect. Furthermore, a superhydrophobic coatings and robust superhydrophobic‐coated cotton woven fabric surfaces were prepared by using PCL‐b‐PTFOA(4h) microspheres with hierarchical structure and low surface energy. The contact angle (CA) and sliding angle (SA) of PCL‐b‐PTFOA(4h) microspheres‐coated cotton woven fabric surfaces reached 164.4 ± 5.5° and 6.8 ± 0.5°, respectively, which allows for self‐cleaning. The self‐cleaning test demonstrated that the coated superhydrophobic surface could shed aqueous dyes and dust without any trace. The superhydrophobic‐coated fabric shows good soaping fastness against mechanical abrasion without significant reduction of CA. This electrospraying coating of block copolymers can provide a simple, facile, and promising technique for producing multifunctional textiles.

Fluorescent-Tagged Biodegradable Polycaprolactone Block Copolymer FRET Probe for Intracellular Bioimaging in Cancer Cells.

The present investigation reports a new fluorophore-tagged biodegradable polycaprolactone (PCL) block copolymer FRET-probe for intracellular imaging in cancer therapy. A hydroxyl functionalized π-conjugated oligo-phenylenevinylene (OPV) chromophore was tailor-made, and it was incorporated in a t-butyl ester substituted polycaprolactone block copolymer via ring opening polymerization. This blue-luminescent OPV-PCL triblock self-assembled as <200 nm spherical nanoparticles (FRET donor), and it encapsulated water insoluble Nile red (NR, FRET acceptor) to yield an OPV-NR FRET probe. Selective photo excitation of the OPV chromophore in block nanoassemblies enabled the excitation energy transfer from the OPV to NR and facilitated the efficient FRET process in aqueous medium. Time-correlated fluorescent decay dynamics and detailed photophysical studies were carried out to estimate the Förster distance, donor-acceptor distance, and the excitation energy transfer efficiency. These parameters confirmed the occurrence of the FRET process within the confined nanoparticle environment. The PCL chains in the FRET probe were susceptible to enzymatic biodegradation in intracellular environments, and the degradation process controlled the FRET on/off mechanism. Cytotoxicity studies revealed that the FRET probe was biocompatible and nontoxic to cells, and the FRET-probe was found to be readily taken up by the cancer cells, and it was internalized in the cytoplasm and peri-nuclear environment. Selective photoexcitation of the OPV chromophore in a confocal microscope exhibited dual emission from the FRET probe. The cancer cells exhibited blue luminescence (self-emission) with respect to the OPV chromophore (in the blue channel) and bright red-luminescence from the NR dye followed by the FRET process at the cellular level (in the red channel). The dual luminescence characteristics, biodegradation and biocompatibility, make the newly designed PCL-OPV-NR FRET probe an excellent biomedical nanodevice for bioimaging applications, and the proof-of-concept was established in cervical (HeLa) and breast cancer (MCF 7) cell lines.

Phosphonium-Functionalized Polymer Micelles with Intrinsic Antibacterial Activity.

New approaches to treat bacterial infections are badly needed to address the increasing problem of antibiotic resistance. This study explores phosphonium-functionalized block copolymer micelles as intrinsically antibacterial polymer assemblies. Phosphonium cations with varying alkyl lengths were conjugated to the terminus of a poly(ethylene oxide)-polycaprolactone block copolymer, and the phosphonium-functionalized block copolymers were self-assembled to form micelles in aqueous solution. The size, morphology, and ζ-potential of the assemblies were studied, and their abilities to kill Escherichia coli and Staphylococcus aureus were evaluated. It was found that the minimum bactericidal concentration depended on the phosphonium alkyl chain length, and different trends were observed for Gram-negative and Gram-positive bacteria. The most active assemblies exhibited no hemolysis of red blood cells above the bactericidal concentrations, indicating that they can selectively disrupt the membranes of bacteria. Furthermore, it was possible to encapsulate and release the antibiotic tetracycline using the assemblies, providing a potential multimechanistic approach to bacterial killing.

Synthesis and characterization of valproic acid ester pro-drug micelles via an amphiphilic polycaprolactone block copolymer design

The attachment of Histone deacetylase (HDAC) inhibitors via covalent bonds to biocompatible and biodegradable block copolymers provides a new research direction for cancer treatment.

In vivo osteogenic differentiation of human turbinate mesenchymal stem cells in an injectable in situ-forming hydrogel

Human turbinate mesenchymal stromal cells (hTMSCs) are an alternate source of adult stem cells for regenerative medicine. In this work, we demonstrated that hTMSCs are easily harvested from turbinate tissue using a minimal surgical procedure. hTMSCs showed positive expression of mesenchymal stem cell markers and proliferated at a high rate. The specific surface proteins of harvested hTMSCs were relatively tolerant of ex vivo manipulation in culture. hTMSCs exhibited osteogenic differentiation in vitro in the presence of osteogenic factors. To examine osteogenic differentiation of hTMSCs in vivo in an injectable hydrogel, cells were incorporated into a methoxy polyethylene glycol–polycaprolactone block copolymer (MPEG–PCL (MP)) solution simply by mixing. hTMSC-loaded MP solutions exhibited a temperature-dependent solution-to-gel phase transition. The hTMSC attached and grew well on in vitro- and in vivo-formed MP hydrogels. hTMSC-loaded MP solutions formed a hydrogel almost immediately upon injection into animals and the cells remained viable, even after 12 weeks. Injected hTMSCs in in situ-formed MP hydrogels differentiated into osteogenic cells, mainly in the presence of osteogenic factors. Differentiated osteoblasts were identified by Alizarin Red S, von Kossa, and alkaline phosphatase (ALP) staining, and osteonectin, osteopontin, and osteocalcin mRNA expression. To the best of our knowledge, this is the first study to show hTMSCs undergoing osteogenic differentiation in in vivo-formed MP hydrogels. In conclusion, hTMSCs could serve as adult stem cell sources and, when embedded in an in situ-formed hydrogel, may provide numerous benefits as a noninvasive alternative for bone tissue engineering applications.

Polyvinylpyrrolidone–polycaprolactone block copolymer micelles as nanocarriers of anti-TB drugs

A range of polyvinylpyrrolidone–polycaprolactone diblock copolymers with varying chain lengths were synthesized by Atom Transfer Radical Polymerisation (ATRP) using bromo-polycaprolactone as macroinitiator and copper(I) bromide/bipyridine catalytic system. The copolymers self-assembled in solution into core–shell micelles with sizes varying from 150 to 205nm and critical micelle concentration of the order of 10−5 to 10−6M. Front line anti-Tuberculosis drugs Rifampicin (RIF), Pyrazinamide (PZA) and Isoniazid (INH) were successfully encapsulated within the micelle hydrophobic core singly or in dual combination. The effect of length of hydrophobic and hydrophilic segments on drug loading, micelle size and drug release was investigated. Determination of binding constants showed that RIF binds more strongly to the micelle core than PZA and INH, leading to highest drug loading content. All drugs were released in vitro (PBS solution at 37°C) in a sustained manner with zero-order kinetics and followed the order INH>PZA>RIF.

Radioisotope carrying polyethylene oxide–polycaprolactone copolymer micelles for targetable bone imaging

The aim of this research is to develop polymeric micelle system as a targetable bone imaging carriers without nonspecific phagocytosis which is made of polyethylene oxide (PEO) and polycaprolactone (PCL). Diamino-PEO, which has two amino groups in its structure, was used to conjugate both PCL and ligand for specific radioisotope. PCL was conjugated to one amino group of diamino-PEO by using diaminohexyl cyclocarbodiimide (DCC), coupling agent. Hydroxyphenylpropionic acid (HPP), diethylenetriamine pentaacetic acid (DTPA) and mercaptoacetyl glycine glycidyl glycine (MAG3), as ligands for specific radioisotopes, were coupled to the rest of amino group of diamino-PEO by the same method as described. Formation of ligand-conjugated block copolymers, critical micelle concentration (CMC) of the copolymers, hydrodynamic radii, and morphology of the micelles were investigated. Besides, 125I-labelling efficiency and biodistribution of the micelles were examined. PEO–PCL block copolymer micelles demonstrated CMC of 25 mg/l and size of 60 nm, which may be adequate for blood vessel and bone imaging. 125I-labelling efficiency was above 90% and was more stable at human serum for 24 h. 125I-labelled polymeric micelles showed higher blood maintenance and bone uptake when compared to stannous colloid, used as a control. A noticeable decrease in liver or spleen uptake could be achieved by the micelles. Therefore, radioisotope carrying PEO–PCL micelle system was suggested as a useful tool for effective diagnostic bone targeting and imaging.

Ultimate properties of epoxy resins modified with a polysiloxane–polycaprolactone block copolymer

AbstractMechanical and fracture mechanics properties of transparent multiphase epoxy resins toughened with various amounts of compatibilized silicone liquid rubbers consisting of polycaprolactone‐block‐poly(dimethylsiloxane)‐block‐polycaprolactone triblock copolymer have been investigated. At silicone liquid rubber contents &lt; 10 wt % significantly improved toughness has been achieved without adversely affecting thermal and mechanical properties. Fractographic and interferometric methods have been applied to study crack propagation in such silicone‐modified resins. © 1994 John Wiley &amp; Sons, Inc.