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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 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.

Rotator cuff tendon repair remains a great challenge in orthopedic surgery. Attempts to inspire the microenvironmental recapitulation from in vivo have rarely elaborated on aligned and reinforced fibrous microtopography required for clinical application. Furthermore, compromises with fibrous densification during fabrication often limit the scaffold’s relevance in translational medicine. Here, we reported a facile and scalable method of uniaxial cold-drawing for engineering tendon patch scaffold. Comprised of bioactive and structure-supporting portions, the scaffold obtained featured microtopography of aligned and sparely-stacked fibres while providing mechanical properties approaching to that of human rotator cuff tendon. The structural integration between scaffold’s two portions resulted in stable and reliable fabrication, where parameters of drawing ratio, speed and temperature influenced the formation of fibrous microtopography. When mesenchymal stem cells were cultured with the scaffold, phenotypic markers of tenogenesis including scleraxis, decorin and tenomodulin were examined higher over nonfibrous controls. Our results further demonstrated that expression of collagen type I was associated with highly aligned intracellular cytoskeleton and the higher nucleus alignment and elongation, coupling with down-regulated cell proliferation and noncytotoxicity.

Abstract The purpose of this study was to investigate the chemical stability and the mechanism of hydrolysis of the polyester wall of lipid-core nanocapsules (LNC) dispersed in water comparing sterile and non-sterile formulations. Sterile or non-sterile LNC formulations (LNCS and LNC, respectively) were prepared using poly(ε-caprolactone) (PCL) with different molar masses (M n 10 kg mol−1, M n 80 kg mol−1 and a mixture (1:9, w /w) of both PCL). All formulations presented unimodal size distribution profile without significant changes (p >.05) after 60 days. Molar weight changes, fraction of chain scissions and hydrolysis mechanism of LNC under storage (60 days; 5 °C) were determined by size exclusion chromatography (SEC). The highest PCL weight loss was observed for the non-sterile formulations (LNC 1–45%; LNC 2–32%; LNC 3–27%). In turn, the sterile formulations showed a lower weight loss, proving that biotic hydrolysis was responsible for accelerating hydrolysis of the LNC even when stored at low temperature (5 °C). In conclusion, the predominant hydrolysis mechanism was of the non-catalyzed type. Graphical abstract Unlabelled Image Highlights • Non-catalyzed hydrolysis mechanism is predominant for the constituents of LNC, except for capric/caprylic triglyceride. • Non-catalyzed mechanism is predominant for all tested formulations. • Storage at low temperatures without sterilization does not guarantee the chemical stability of lipid-core nanocapsules. [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]

Design and fabrication of scaffolds using appropriate biomaterials are a key step for the creation of functionally engineered tissues and their clinical applications. Poly(epsilon-caprolactone) (PCL), a biodegradable and biocompatible material with negligible cytotoxicity, is widely used to fabricate nanofiber scaffolds by electrospinning for the applications of pharmaceutical products and wound dressings. However, the use of PCL as such in tissue engineering is limited due to its poor bioregulatory activity, high hydrophobicity, lack of functional groups and neutral charge. With the attempt to found nanofiber scaffolds with antibacterial activity for skin tissue engineering, in this study, whey protein concentrate (WPC) was used to modify the PCL nanofibers by doping it in the PCL electrospun solution. By adding proteins into PCL nanofibers, the degradability of the fibers may be increased, and this further allows an antibiotic incorporated in the fibers to be efficiently released. The morphology, wettability and degradation of the as-prepared PCL/WPC nanofibers were carefully characterized. The results showed that the PCL/WPC nanofibers possessed good morphology and wettability, as well as high degradation ability to compare with the pristine PCL fibers. Afterwords, tetracycline hydrochloride as a model antibiotic drug was doped in the PCL/WPC nanofibers. In vitro drug release assays demonstrated that PCL/WPC nanofibers had higher antibiotic release capability than the PCL nanofibers. Also, antibacterial activity evaluation against various bacteria showed that the drug-doped PCL/WPC fibers possessed more efficient antibacterial activity than the PCL nanofibers. [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]

Poly(epsilon-caprolactone)/corn starch blends containing 25, 50 and 75 wt.% starch were prepared by mechanical processing and characterized by the melt flow index (MFI), tensile test and scanning electron microscopy (SEM). For comparison, starch was used in gelatinized and nongelatinized forms and was also characterized by viscography. The addition of starch to poly(epsilon-caprolactone) reduced the MFI values, the tensile strength and the elongation at break, whereas the modulus increased. The reductions in the MFI and tensile properties were most evident when gelatinized starch was used. Viscography and SEM showed that starch was well gelatinized by the gelatinization process. Blends containing nongelatinized starch showed a good dispersion of starch but poor interfacial interactions.

Drug delivery into hair follicles with the use of nanoparticles (NPs) is gaining more importance as drug-loaded NPs may accumulate in hair follicle openings. The aim was to develop and evaluate a pluronic lecithin organogel (PLO) with roxithromycin (ROX)-loaded NPs for follicular targeting. Polymeric NPs were evaluated in terms of particle shape, size, zeta potential, suspension stability, encapsulation efficiency and in vitro drug release. Lyophilized NPs were incorporated into the PLO and rheological measurements of the nanoparticles-embedded organogels were done. The fate of the NPs in the skin was traced by incorporation of a fluorescent dye into the NPs. As a result, ROX was efficiently incorporated into polymeric NPs characterized by the appropriate size (approximately 300 nm) allowing drug delivery to hair follicles. In ex vivo human skin penetration studies, horizontal skin sections revealed fluorescence deep in the hair follicles. Although the organogel has higher affinity to the lipidic follicular area than an aqueous suspension of NPs, it did not seem to improve penetration of the NPs along the hair shaft. The results proved that it was possible to achieve preferential targeting to the pilosebaceous unit using polymeric NPs formulated either into the aqueous suspension or semisolid topical formulation. [ABSTRACT FROM AUTHOR]

Periosteum is clinically required for the management of large bone defects. Attempts to exploit the periosteum's participation in bone healing, however, have rarely featured biological and mechanical complexity for the scaffolds relevant to translational medicine. In this regard, we report engineering of bioinspired periosteum with co-delivery of ionic and geometry cues. The scaffold demonstrated microsheet-like fibre morphology and was developed based on bioresorbable poly(-caprolactone) and bioactive copper-doped tricalcium phosphate (Cu-TCP). A coordinated interaction was found between the effects of Cu-TCP addition and uniaxial drawing, leading to tunable fibrogenesis for different fibre morphologies, organisation, and surface wettability. The coordination resulted in significant enhancements in Young's Modulus, yield stress and ultimate stress along fibrous alignment, without causing reductions across fibres. This demonstrated mechanical anisotropy of the scaffold similar to natural periosteum, and seeding with mouse calvarial preosteoblasts, the scaffold supported cell alignment with deposition of CaP-like nodules and extracellular matrix. This work provides new insights on periosteum engineering with osteo-related composite fibres. The artificial periosteum can be used in clinical settings to facilitate repair of large bone defects. [Display omitted] • Integration of ionic and geometric cues drives bionic periosteum engineering. • Composition and fabrication can tailor fibrogenesis coordinately. • Enhanced mechanics approach natural periosteum at magnitude and anisotropy. • Biological guidance on cell structure and excellular matrix supports bone application. [ABSTRACT FROM AUTHOR]

Nanocarriers may provide interesting delivery platforms for microbicide drugs and their characterization should be addressed early in development. Differently surface-engineered dapivirine-loaded, poly(epsilon-caprolactone) (PCL)-based nanoparticles (NPs) were obtained by nanoprecipitation using polyethylene oxide (PEO), sodium lauryl sulfate (SLS), or cetyltrimethylammonium bromide (CTAB) as surface modifiers. Physical–chemical properties of NP aqueous dispersions were evaluated upon storage at −20–40°C for one year. NPs presented 170–200nm in diameter, roundish-shape, low polydispersity index (≤0.18), and high drug association efficiency (≥97%) and loading (≥12.7%). NPs differed in zeta potential, depending on surface modifier (PEO: −27.9mV; SLS: −54.7mV; CTAB: +42.4mV). No interactions among formulation components were detected by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), except for SLS–PCL NPs. Colloidal properties of NPs were lost at −20°C storage. Negatively charged NPs were stable up to one year at 5–40°C; as for CTAB–PCL NPs, particle aggregation was observed from 30 to 90 days of storage depending on temperature. Colloidal instability affected the in vitro drug release of CTAB–PCL NPs after 360 days. In any case, no degradation of dapivirine was apparent. Overall, PEO–PCL and SLS–PCL NPs presented suitable properties as nanocarriers for dapivirine. Conversely, CTAB–PCL NPs require additional strategies in order to increase stability. [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]

Abstract: A novel approach for vascular grafts to achieve rapid endothelialization is to attract endothelial progenitor cells (EPCs) from peripheral blood onto grafts via EPC-specific antibodies, aptamer, or peptides that specifically bind to EPCs. Inspired by this idea, the electrospun poly(epsilon-caprolactone) (PCL) mats were modified with zwitterionic poly(carboxybetaine methacrylate) (PCBMA) and phage display-selected-EPC-specific peptide, TPSLEQRTVYAK (TPS). We tested the physical and chemical properties, cyto-compatibility, and platelet adhesion of the modified material, and investigated the specificity of the functionalized surface for capturing EPCs. The results indicated that PCL modified with zwitterionic PCBMA and TPS peptide showed improved hydrophilicity without morphology change and damage of the mats. Furthermore, the modified material supported adherence and growth of vascular cells and resisted platelets adhesion. The surfaces also specifically captured EPCs rather than bone marrow mesenchymal stem cells and human umbilical vein endothelial cells. This surface-functionalized PCL graft may offer new opportunities for designing new vascular grafts. [Copyright &y& Elsevier]

Abstract: Poly(epsilon-caprolactone)/clay nanocomposites were prepared by copper(I) catalyzed azide/alkyne cycloaddition (CuAAC) “click” reaction. In this method, ring-opening polymerization of epsilon-caprolactone using propargyl alcohol as the initiator has been performed to produce alkyne-functionalized PCL and the obtained polymers were subsequently attached to azide-modified clay layers by a CuAAC “click” reaction. The exfoliated polymer/clay nanocomposites were characterized by X-ray diffraction spectroscopy, thermogravimetric analysis and transmission electron microscopy. [Copyright &y& Elsevier]

Abstract: A series of poly(epsilon-caprolactone) (PCL)-based multilayered films containing antitumor 5-fluorouracil as stent struts were produced. A backing layer and a surface drug layer were applied to the main drug layer to realize unidirectional, controlled drug release and enhance the mechanical properties. The intricate multilayered structure endowed the films with flexibility to regulate drug release. The in vitro release results showed that drug release was dependent on the drug loading and environmental pH, and could also be effectively regulated by addition of hydrophilic PEG as pore forming agent. Drug release from the multilayered film was found to be dominated by diffusion mechanism. Rapid PEG release led to the formation of pores and the resulting fast drug release. SEM images revealed that the 5-FU crystalline particles were homogeneously dispersed in the film, and there emerged many pores on the surface and in the bulk of film after PEG and drug release, indicating that the porous structure of film was formed and gradually evolved with drug and PEG release. Ex vivo permeation behaviors of drug from the film through porcine esophageal mucosa were in high correlation with the in vitro release behaviors, and the permeation rate was determined by the release of drug from film. With the virtue of releasing drug in a unidirectional and controlled manner, the multilayered films provide an attractive mode to produce polymeric drug delivery stents for localized treatment of stenosis or occlusion. [Copyright &y& Elsevier]

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]

Abstract: The aim of this work was to design injectable nanocarriers for drug delivery based on PCL–PEO amphiphilic block copolymers with linear ABA triblock and 4-armed (BA)4 star-diblock architectures (A=PEO, B=PCL). The copolymers were obtained by coupling of a monofunctional –COOH end-capped PEO (M n =2.0kDa) with linear or 4-armed star-shaped PCL macromers bearing –OH terminal groups and were characterized by 1H NMR spectroscopy and size exclusion chromatography. DSC and X-ray diffraction experiments showed that separate crystalline phases of PCL and PEO are present in bulk copolymers. Nanoparticles were produced by nanoprecipitation (NP) and by a new melting-sonication procedure (MS) without the use of toxic solvents, and characterized for size, polydispersity, zeta potential and core-shell structure. Nanoparticles were loaded with all-trans-retinoic acid (atRA) as a model drug and their release features assessed. Results demonstrate that both techniques allow the formation of PEO-coated nanoparticles with a hydrodynamic diameter that is larger for nanoparticles prepared by MS. atRA is released from nanoparticles at controlled rates depending on size, loading and, more important, preparation technique, being release rate faster for MS nanoparticles. Some biorelevant properties of the carrier such as complement activation were finally explored to predict their circulation time after intravenous injection. It is demonstrated that nanoparticles prepared by MS do not activate complement and are of great interest for future in vivo applications. [Copyright &y& Elsevier]

Abstract: Since dextran (DEX) grafted with poly(ε-caprolacton) (PCL) side chains (PCL–DEX) copolymers could form nanoparticles with a well defined core-shell structure, we investigated the ability of the DEX coating to modify the interactions with the biological media. We first studied the influence of the DEX coating on the phagocytosis of the nanoparticles by human TPH-1 and J774 murine macrophage-like cell lines. Then, the activation of the complement system (CH50 measurement) at the surface of the particles and the adsorption of plasma proteins (2D-PAGE) were investigated, too. It was found that the modification of the surface with DEX significantly reduced the cytotoxicity towards J774 macrophages: the IC50 was increased from 10 to 600μg/ml. However, the DEX coating could activate complement, probably due to a loop-like conformation of DEX similar to that of cross-linked DEX in Sephadex (a strong complement activator). In addition, depending on whether the DEX loops were large or compact, preferential adsorption, apolipoproteins or immunoglobulins, was observed. [Copyright &y& Elsevier]

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]