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As a biodegradable polyester, the commercialized synthesis protocol of poly(ε-caprolactone) (PCL) under mild conditions is of great significance and attractive. Herein, the ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) using FeCl3 catalyst and benzyl alcohol (BnOH) as the initiator was developed. FeCl3 has been proved to be an efficient catalyst for the ROP of ε-CL under mild conditions. The conversion of ε-CL to PCL was 98.8% at 60 °C within 4 h, with number-average molecular weight (Mn) and dispersity (PDI) of 1.65 × 104 g/mol and 1.28, respectively. Moreover, a coordination-insertion ring-opening polymerization mechanism mediated by FeCl3 was proposed. Overall, this work is expected to provide a feasible industrial method for the preparation of PCL from the direct aerobic oxidation of cyclohexanone. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD), a non-psychoactive constituent of Cannabis, has proven neuroprotective, anti-inflammatory and antioxidant properties though his therapeutic use, especially by the oral route, is still challenged by the poor aqueous solubility that results in low oral bioavailability. In this work, we investigate the encapsulation of CBD within nanoparticles of a highly hydrophobic poly(ethylene glycol)-b-poly(epsilon-caprolactone) block copolymer produced by a simple and reproducible nanoprecipitation method. The encapsulation efficiency is ~ 100% and the CBD loading 11% w/w (high performance liquid chromatography). CBD-loaded nanoparticles show a monomodal size distribution with sizes of up to 100 nm (dynamic light scattering), a spherical morphology, and the absence of CBD crystals (high resolution-scanning electron microscopy and cryogenic-transmission electron microscopy) which is in line with a very efficient nanoencapsulation. Then, the CBD release profile from the nanoparticles is assessed under gastric- and intestine-like conditions. At pH 1.2, only 10% of the payload is released after 1 h. Conversely, at pH 6.8, a release of 80% is recorded after 2 h. Finally, the oral pharmacokinetics is investigated in rats and compared to a free CBD suspension. CBD-loaded nanoparticles lead to a statistically significant ~ 20-fold increase of the maximum drug concentration in plasma (Cmax) and a shortening of the time to the Cmax (tmax) from 4 to 0.3 h, indicating a more complete and faster absorption than in free form. Moreover, the area-under-the-curve (AUC), a measure of oral bioavailability, increased by 14 times. Overall results highlight the promise of this simple, reproducible, and scalable nanotechnology strategy to improve the oral performance of CBD with respect to common oily formulations and/or lipid-based drug delivery systems associated with systemic adverse effects. [ABSTRACT FROM AUTHOR]

In this work, composite electrospun fibers containing innovative bioactive glass nanoparticles were produced and characterized. Poly(ε‐caprolactone), benign solvents, and sol–gel B‐ and Cu‐doped bioactive glass powders were used to fabricate fibrous scaffolds. The retention of bioactive glass nanoparticles in the polymer matrix, the electrospinnability of this novel solution and the obtained electrospun composites were extensively characterized. As a result, composite electrospun fibers characterized by biocompatibility, bioactivity, and exhibiting overall properties adequate for both hard and soft tissue engineering applications, have been produced. The addition of these bioactive glass nanoparticles was, indeed, able to impart bioactive properties to the fibers. Cell culture studies show promising results, demonstrating proliferation and growth of cells on the composite fibers. Wettability, degradation rate, and mechanical performance were also tested and are in line with previous results. [ABSTRACT FROM AUTHOR]

The number of effective herbicides available to farmers is steadily decreasing due to increasing herbicide resistance. It seems very important to address and effectively deal with the main weed management challenges (low crop yield and environmental pollution) by investigating the potential of newly introduced materials, such as biocompatible polymer-based nanoparticles. The current review aims to encourage agricultural or environmental researchers to conduct new research on the synthesis and application of modified herbicides, such as nanoherbicides, for application in weed management and to provide a comprehensive foundation on the topic. Such nanosystems could help with the promotion of the controlled release of active ingredients and extend their action time, resulting in a reduction in dose and application number; improve the physical and chemical characteristics of the herbicide to increase foliar adhesion; prevent degradation that results from environmental factors (such as sunlight, temperature, microorganisms, or pH); and decrease herbicide leaching and contamination of the environment. Furthermore, it has been indicated that some polymeric nanocarriers can penetrate biological barriers, including membranes and plant cell walls, and translocate across vascular tissues, resulting in a more efficient delivery of active ingredients. Poly(epsilon-caprolactone) is a biocompatible material that is easily decomposable by enzymes and fungi. PCL nanoparticles could be applied as nanocarriers of herbicides in agriculture due to their low toxicity, their potential for large-scale synthesis from inexpensive materials, their ability to dissolve herbicides, their high loading capacity, and their ability to help minimize the chemical decomposition of herbicides. [ABSTRACT FROM AUTHOR]

The electrospinning technique is a versatile method for the production of fibrous scaffolds able to resemble the morphology of the native extra cellular matrix. In the present paper, electrospinning is used to fabricate novel SiO2 particles (type MCM-41) containing poly(epsilon-caprolactone) (PCL) fibers. The main aims of the present work are both the optimization of the particle synthesis and the fabrication of composite fibers, obtained using benign solvents, suitable as drug delivery systems and scaffolds for soft tissue engineering applications. The optimized synthesis and characterization of calcium-containing MCM-41 particles are reported. Homogeneous bead-free composite electrospun mats were obtained by using acetic acid and formic acid as solvents; neat PCL electrospun mats were used as control. Initially, an optimization of the electrospinning environmental parameters, like relative humidity, was performed. The obtained composite nanofibers were characterized from the morphological, chemical and mechanical points of view, the acellular bioactivity of the composite nanofibers was also investigated. Positive results were obtained in terms of mesoporous particle incorporation in the fibers and no significant differences in terms of average fiber diameter were detected between the neat and composite electrospun fibers. Even if the Ca-containing MCM-41 particles are bioactive, this property is not preserved in the composite fibers. In fact, during the bioactivity assessment, the particles were released confirming the potential application of the composite fibers as a drug delivery system. Preliminary in vitro tests with bone marrow stromal cells were performed to investigate cell adhesion on the fabricated composite mats, the positive obtained results confirmed the suitability of the composite fibers as scaffolds for soft tissue engineering. [ABSTRACT FROM AUTHOR]

The electrospinning technique is widely used for the fabrication of micro- and nanofibrous structures. Recent studies have focused on the use of less toxic and harmful solvents (benign solvents) for electrospinning, even if those solvents usually require an accurate and longer process of optimization. The aim of the present work is to demonstrate the versatility of the use of benign solvents, like acetic acid and formic acid, for the fabrication of microfibrous and nanofibrous electrospun poly(epsilon-caprolactone) mats. The solvent systems were also shown to be suitable for the fabrication of electrospun structures with macroporosity, as well as for the fabrication of composite electrospun mats, fabricated by the addition of bioactive glass (45S5 composition) particles in the polymeric solution. [ABSTRACT FROM AUTHOR]

Current treatments available for human immunodeficiency virus, namely antiretrovirals, do not completely eradicate the virus from the body, leading to life-time commitment. Many antiretrovirals suffer drawbacks from toxicity and unpleasant side effects, causing patience non-compliance. To minimize challenges associated with the antiretrovirals, biodegradable nanoparticles used as drug delivery systems hold tremendous potential to enhance patience compliance. The main objective of this work was to load lamivudine (LAM) into poly(epsilon-caprolactone) (PCL) nanoparticles. LAM is a hydrophilic drug with low plasma half-life of 5–7 h and several unpleasant side effects. LAM was nanoencapsulated into PCL polymer via the double emulsion spray-drying method. Formulation parameters such as the effect of solvent, excipient and drug concentration were optimized for the synthesis of the nanoparticles. Spherical nanoparticles with an average size of 215 ± 3 nm and polydispersity index (PDI) of 0.227 ± 0.01 were obtained, when ethyl acetate and lactose were used in the preparation. However, dichloromethane presented sizes larger than 454 ± 11 nm with PDI of more than 0.4 ± 0.05, irrespective of whether lactose or trehalose was used in the preparation. Some of the nanoparticles prepared with trehalose resulted in crystal formation. UV spectroscopy showed encapsulation efficiency ranging from 68 ± 4 to 78 ± 4 % for LAM depending on the starting drug concentration. Fourier transform infrared spectroscopy and X-ray diffraction confirmed the possibility of preparing amorphous PCL nanoparticles containing LAM. Drug release extended for 4 days in pH 1.3, pH 4.5 and pH 6.8. These results indicated that LAM-loaded PCL nanoparticles show promise for controlled delivery. [ABSTRACT FROM AUTHOR]

The main purpose of this study was to obtain COOH functionalities on the surface of poly-ε-caprolactone (PCL) membranes using low-pressure water/O2-plasma-assisted treatment. PCL membranes were prepared using the solvent-casting technique. Then, low-pressure water/O2 plasma treatments were performed in a cylindrical, capacitively coupled RF-plasma-reactor in three steps: H2O/O2-plasma treatment; in situ (oxalyl chloride vapors) gas/solid reaction to convert –OH functionalities into –COCl groups; and hydrolysis for final –COOH functionalities. Optimization of plasma modification processes was done using the DoE software program. COOH and OH functionalities on modified surfaces were detected quantitatively using the fluorescent labeling technique and an UVX 300G sensor. Chemical structural information of untreated, plasma treated and oxalyl chloride functionalized PCL membranes were acquired using pyrolysis GC/MS and ESCA analysis. High-resolution AFM images revealed that nanopatterns were more affected than micropatterns by plasma treatments. AFM images recorded with amino-functionalized tips presented increased size of the features on the surface that suggests higher density of the carboxyls on the nanotopographical elements. Low-pressure water/O2-plasma-treated and oxalyl chloride functionalized samples were biologically activated with insulin and/or heparin biosignal molecules using a PEO (polyoxyethylene bis amine) spacer. The success of the immobilization process was checked qualitatively by ESCA analysis. In addition, fluorescent labeling techniques were used for the quantitative determination of immobilized biomolecules. Cell-culture experiments indicated that biomolecule immobilization onto PCL scaffolds was effective on L929 cell adhesion and proliferation, especially in the presence of heparin. [ABSTRACT FROM AUTHOR]

In this study, the effect of MDR-1 gene silencing, using small interfering RNA (siRNA), and paclitaxel (PTX) co-therapy in overcoming tumor multidrug resistance was examined. Poly(ethylene oxide)-modified poly(beta-amino ester) (PEO-PbAE) and PEO-modified poly(epsilon-caprolactone) (PEO-PCL) nanoparticles were formulated to efficiently encapsulate MDR-1 silencing siRNA and PTX, respectively. Upon administration in multidrug resistant SKOV3TR human ovarian adenocarcinoma cells, siRNA-mediated MDR-1 gene silencing was evident at 100 nM dose. Combination of MDR-1 gene silencing and nanoparticle-mediated delivery significantly influenced the cytotoxic activity of PTX in SKOV3TR cells similar to what was observed in drug sensitive SKOV3 cells. We speculate that the enhancement in cytotoxicity was due to an increase in intracellular drug accumulation upon MDR-1 gene silencing leading to an apoptotic cell-kill effect. Taken together, these preliminary results are highly encouraging for the development of combination nano-therapeutic strategies that combine gene silencing and drug delivery to provide more potent therapeutic effect, especially in refractory tumors. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the anti-tumor efficacy and lack of systemic toxicity of paclitaxel when administered in pH-sensitive poly(ethylene oxide) (PEO)-modified poly(beta-amino ester) (PbAE) nanoparticles in mice bearing human ovarian adenocarcinoma (SKOV-3) xenograft. Paclitaxel-encapsulated PEO-modified PbAE (PEO–PbAE) nanoparticles were prepared by the solvent displacement method. PEO-modified poly(epsilon-caprolactone) (PCL) (PEO–PCL) nanoparticles were used as a non pH-responsive control formulation. Efficacy studies were conducted in SKOV-3 tumor-bearing athymic (Nu/Nu) mice at an equivalent paclitaxel dose of 20 mg/kg with the control and nanoparticle formulations. Safety of the drug when administered in the control and nanoparticle formulation was determined from blood cell counts and changes in body weight of the animals. The formulated paclitaxel-containing PEO–PbAE and PEO–PCL nanoparticles had a particle size in the range of 100–200 nm and a surface charge of + 39.0 and − 30.8 mV, respectively. After intravenous administration of paclitaxel in these formulations, the tumor growth was inhibited significantly. Both of the formulated nanoparticles tested have shown improved therapeutic efficacy as compared to the paclitaxel aqueous solution. Additionally, significantly lower toxicity profile of paclitaxel was observed with PEO-modified nanoparticles as compared to the aqueous solution formulation PEO-modified PbAE nanoparticles are a unique pH-sensitive drug delivery system that elicits enhanced efficacy and safety profile in solid tumor therapy. [ABSTRACT FROM AUTHOR]

Degradable terpolymers were synthesized by bulk copolymerization of 2,2-dimethyl trimethyle necarbonate (DTC), ε-caprolactone (CL) and poly(ethylene glycol) (PEG) using stannous octoate as catalyst at 140°C for 36 h. The molar ratio in feed of DTC to CL was fixed at 20 : 80. The molecular weight and the mol% of PEG were varied in order to obtain copolymers with different properties. The copolymers were characterized by [sup 1]H-NMR, [sup 13]C-NMR, FT-IR, GPC and DSC. It was found that the hydrophilicity of these materials increased with increasing PEG content in the copolymers, according to the measurements of static contact angles of distilled water on the surface of polymer films. Mechanical tests and hydrolytic degradation assays showed that copolymers of different degradability and mechanical properties could be tailored by adjusting the compositions. For the copolymer T-4 (11.9 mol% of PEG with M[sub n] 2000), the tensile strength and the elastic modulus could reach 6.2 MPa and 25 MPa, respectively. It took only 4 weeks for the copolymer T-4 to degrade to 83% (M[sub n,t]/M[sub n,0]) and 10 weeks to 63% in 0.1 M PBS at pH 7.4 and 37°C. There was no obvious acceleration of degradation rate in vivo in comparison with that in vitro. These materials might be useful for nerve regeneration guides and other biomedical applications. [ABSTRACT FROM AUTHOR]

Catalyzed Ring-Opening Polymerization (ROP) of lactones, such as ε-caprolactone and δ-valerolactone, has been investigated for preparing aliphatic polyester-grafted corn starch compositions. The polymerization has been carried out either in bulk (without solvent) or in 10 wt% granular starch in toluene suspension, after adequate activation of the starch surface amylose/amylopectin hydroxyl groups into aluminum alkoxides. This activation has been done by in situ reaction with triethylaluminum and has proved to be very effective in promoting fast ROP and also covalent grafting of the polyester chains onto the starch surface. Drying of the starch granules constitutes a key-step of the proposed process. The actual fixation of the initiator onto the starch surface has been checked by XPS analysis whereas good adhesion between the two components has been evidenced by SEM observations. Growth of the polyester chains on the starch granules has been followed by the increase of the mean diameter of the 'encapsulated' granules as attested by laser scattering granulometry. [ABSTRACT FROM AUTHOR]

Nonwoven membranes of poly(ε‐caprolactone) (PCL) and chitosan (CS) were produced according to the two methods: by blending the polymers in solution followed by electrospinning – polymer blending method – and by simultaneous deposition of fibers electrospun from separate solutions – fiber blending (FB) method. The two production methods were compared by assessing fiber morphology, mass loss, swelling degree, water contact angle, and mechanical properties of the resulting electrospun membranes. Furthermore, the adhesion, proliferation, and morphology of human dermal fibroblasts on the eight types of scaffold produced were evaluated to assess if the blending method used would influence cell–scaffold interaction. Cell adhesion to the different scaffolds lied in the interval 40–60%, with the CS scaffold presenting the lowest value. Interestingly, cell proliferation was the same when comparing polymer blending and FB scaffolds having 3:1 or 1:3 PCL/CS ratios but very different when the ratio was 1:1 – the FB scaffold sustained a proliferation rate double that of the polymer blending scaffold. This work shows that, when blending polymers to improve the properties of a scaffold for tissue engineering or 3D cell culture, their spatial distribution may considerably affect scaffold's properties and should be considered as another parameter requiring optimization. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47191. [ABSTRACT FROM AUTHOR]