Ruxolitinib-loaded poly-ɛ-caprolactone (PCL) nanoparticles inhibit JAK2/STAT5 signaling in BT474 breast cancer cells by downregulating Bcl-2 and Mcl-1.

BACKGROUND: JAK/STAT signaling plays an important role in regulating cell proliferation. Reducing proliferation and inducing cell death with gene-specific inhibitors such as ruxolitinib, Receptor tyrosine kinases (RTK) inhibitor targeting JAK1/2, are therapeutic approaches. The use of nanoparticles can reduce the toxicity and side effects of drugs, as they act directly on cancer cells and can selectively increase drug accumulation in tumor cells. Poly-ɛ-caprolactone (PCL) is a polymer that is frequently used in drug development. In this study, Rux-PCL-NPs were synthesized to increase the effectiveness of ruxolitinib. In addition, this study aimed to determine the effect of Rux-PCL-NPs on JAK/STAT signaling and apoptotic cell death. METHODS AND RESULTS: Rux-PCL-NPs were synthesized by nanoprecipitation. The Rux-PCL-NPs had a spherical and mean particle size of 219 ± 88.66 nm and a zeta potential of 0.471 ± 0.453 mV. In vitro cytotoxicity and antiproliferative effects were determined by MTT and soft agar colony formation assays, respectively. The effects of ruxolitinib, PCL-NPs, and Rux-PCL-NPs on apoptosis and the JAK/STAT pathway in cells were examined by western blot analysis. PCL-NPs did not have a toxic effect on the cells. The IC50 value of Rux-PCL-NPs was decreased 50-fold compared to that of ruxolitinib. Rux-PCL-NPs promoted cell death by downregulating JAK2 and STAT5, thereby inhibiting the JAK/STAT pathway. CONCLUSIONS: Our results revealed that Rux-PCL-NPs, which increased the efficacy of ruxolitinib, regulated apoptosis and the JAK2/STAT5 pathway.

Total meniscus replacement with a 3D printing of network hydrogel composite scaffold in a rabbit model.

PURPOSE: The aim of this study was to evaluate the role of a novel total meniscal implant in promoting meniscal regeneration and protecting articular cartilage in a rabbit model for 3 and 6 months. METHODS: Thirty-six New Zealand rabbits were selected and divided into poly(ɛ-caprolactone) (PG-Pg) scaffold group, meniscectomy group and sham group. In this study, it was investigated whether PG-Pg scaffold can prevent articular cartilage degeneration and promote tissue degeneration, and its mechanical properties at 3 and 6 months after surgery were also explored. RESULT: The degree of articular cartilage degeneration was significantly lower in the PG-Pg scaffold group than in the meniscectomy group. The number of chondrocytes increased in the PG-Pg scaffold at 3 and 6 months, while a gradual increase in the mechanical properties of the PG-Pg stent was observed from 6 months. CONCLUSION: The PG-Pg scaffold slows down the degeneration of articular cartilage, promotes tissue regeneration and improves biomechanical properties after meniscectomy. This novel meniscus scaffold holds promise for enhancing surgical strategies and delivering superior long-term results for individuals with severe meniscus tears. LEVEL OF EVIDENCE: NA.

Evaluation of Porous (Poly(lactide-co-glycolide)-co-(ε-caprolactone)) Polyurethane for Use in Orthopedic Scaffolds.

To develop an orthopedic scaffold that could overcome the limitations of implants used in clinics, we designed poly(ester-urethane) foams and compared their properties with those of a commercial gold standard. A degradable poly(ester-urethane) was synthetized by polyaddition between a diisocyanate poly(ε-caprolactone) prepolymer (PCL di-NCO, Mn = 2400 g·mol-1) and poly(lactic-co-glycolic acid) diol (PLGA, Mn = 2200 g·mol-1) acting as a chain extender. The resulting high-molecular-weight poly(ester-urethane) (PEU, Mn = 87,000 g·mol-1) was obtained and thoroughly characterized by NMR, FTIR and SEC-MALS. The porous scaffolds were then processed using the solvent casting (SC)/particle leaching (PL) method with different NaCl crystal concentrations. The morphology, pore size and porosity of the foams were evaluated using SEM, showing interconnected pores with a uniform size of around 150 µm. The mechanical properties of the scaffolds are close to those of the human meniscus (Ey = 0.5~1 MPa). Their degradation under accelerated conditions confirms that incorporating PLGA into the scaffolds greatly accelerates their degradation rate compared to the gold-standard implant. Finally, a cytotoxicity study confirmed the absence of the cytotoxicity of the PEU, with a 90% viability of the L929 cells. These results suggest that degradable porous PLGA/PCL poly(ester-urethane) has potential in the development of meniscal implants.

Penicillium fellutanum lipase as a green and ecofriendly biocatalyst for depolymerization of poly (ɛ-caprolactone): Biochemical, kinetic, and thermodynamic investigations.

Microbial lipases hold a prominent position in biocatalysis by their capability to mediate reactions in aqueous and nonaqueous media. Herein, a lipase from Penicillium fellutanum was biochemically characterized and investigated its potential to degrade poly (ɛ-caprolactone) (PCL). The lipase exhibited stability over a broad pH spectrum and performed best at pH 8.5 and 45 °C. The activation energy was determined to be 66.37 kJ/mol by Arrhenius plot, whereas Km and Vmax for pNPP hydrolysis were 0.75 mM and 83.33 µmol/mL/Min, respectively. A rise in temperature reduced the Gibbs free energy, whereas the enthalpy of thermal unfolding (∆H*) remains the same up to 54 °C following a modest decline at 61 °C. The entropy (∆S*) of the enzyme demonstrated an increasing trend up to 54 °C and dropped at 61 °C. Lipase retained stability by incubation with various industrially relevant organic solvents (benzene, hexanol, ether, and acetone). However, exposure to urea and guanidine hydrochloride influenced its catalytic activity to different extents. Under optimal operating conditions, lipase catalyzed the excellent degradation of PCL film degradation leading to 66% weight loss, increased surface erosion, and crystallinity. Fourier-transform infrared spectrometry, differential scanning calorimetry, and scanning electron microscopy studies monitored the weight loss after enzymatic hydrolysis. The findings indicate that P. fellutanum lipase would be a prospective biocatalytic system for polyesters depolymerization and environmental remediation.

Lamellar Assembly Mechanism on Dendritic Ring-Banded Spherulites of Poly(ε-caprolactone).

The self-assembly structures of lamellae in optical ring bands have a critical effect on their optical and physical arrangements. Two different types of dendritic banded spherulites (namely ring-banded and zigzag ring-banded) are formed in poly(ε-caprolactone)/poly (phenyl methacrylate) blend at crystallization temperatures of 42 and 46 °C, respectively. The difference in optical birefringence of ring bands in two types of spherulites is resolved by means of direct morphological comparison. Banded spherulites are fractured carefully to facilitate lamellar orientation analyses of both the top surface and the interior surface. The results have revealed the existence of tree-like dendritic fractal growth lamellar assemblies in both banded spherulites. The optical ring patterns of the banded spherulites are differentiated mainly by the fractal orientation of the edge-on crystal branches in the ridge region. On the basis of detailed morphological analysis, 3D-lamellar assembly mechanisms are proposed to explain the growth of dendritic ring-banded spherulites at 42 °C and dendritic zigzag ring-banded spherulites at 46 °C.

Spray coating of foley urinary catheter by chlorhexidine-loadedpoly(ε-caprolactone) nanospheres: effect of lyoprotectants, characteristics, and antibacterial activity evaluation.

In this study, chlorhexidine-loaded poly(ε-caprolactone) nanospheres (CHX-NS) were prepared and successfully coated on the urinary catheters. Properties of CHX-NS were evaluated including drug loading content and the nanosphere size. Effects of different lyoprotectants for long-term storage of CHX-NS were also investigated. In vitro release study and antibacterial activity were also conducted using 20 cycles coated-urinary catheters. Results showed that the high-pressure emulsification-solvent evaporation technique provided the drug loading content at 1.14 ± 0.16% and the size of nanospheres was 152 ± 37 nm. The suitable lyoprotectant for long-term storage of CHX-NS was sucrose which provided noticeably no aggregation at the degree of reconstitution at 89.95%. The amount of CHX loading on coated catheters was at 4.55 ± 0.31 mg. Drug release from the coated catheters in artificial urine could be prolonged up to 2 weeks and bacteria proliferation was inhibited up to 14 days. These results suggest that the antimicrobial activity of CHX-NS reduces the adherence of the uropathogens to the catheter surface. Chlorhexidine-loaded polymeric nanospheres were fabricated which can be successfully coated on urinary catheters. These systems have potential use for prolonged antimicrobial applications.

Study of poly-ɛ-caprolactone membranes for pleurodesis.

BACKGROUND/PURPOSE: Pleurodesis with biomaterial membrane is an emerging treatment method for pneumothorax. However, the ideal one for the common disease is still under debate. METHODS: We investigate the Poly-ε-caprolactone (PCL) membrane pleurodesis by using New Zealand White rabbits, which was sacrificed for examination one month later. Moreover, inflammation and fibrosis scoring were done under microscopic evaluation, as well as Western blot analysis in vitro and in vivo. RESULTS: Gross evaluation of pleurodesis score revealed that dense PCL membrane produced moderate pleural adhesion, while porous PCL membrane exhibited significantly higher pleurodesis scores. CONCLUSION: PCL membrane induced significant degree of adhesion, both within the abdomen and chest of the rabbits. The porous PCL membrane produces more intensive adhesion than dense one. Fibronectin plays an important role in the process of pleurodesis. Further study is required for the clinical application of the promising material.

Freeze drying optimization of polymeric nanoparticles for ocular flurbiprofen delivery: effect of protectant agents and critical process parameters on long-term stability.

CONTEXT: The stabilization of flurbiprofen loaded poly-ɛ-caprolactone nanoparticles (FB-PɛCL-NPs) for ocular delivery under accurate freeze-drying (FD) process provides the basis for a large-scale production and its commercial development. OBJECTIVE: Optimization of the FD to improve long-term stability of ocular administration's FB-PɛCL-NPs. METHODS: FB-PɛCL-NPs were prepared by solvent displacement method with poloxamer 188 (P188) as stabilizer. Freezing and primary drying (PD) were studied and optimized through freeze-thawing test and FD microscopy. Design of experiments was used to accurate secondary drying (SD) conditions and components concentration. Formulations were selected according to desired physicochemical properties. Furthermore, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to study interactions components. RESULTS: Optimized FB-PɛCL-NPs, stabilized with 3.5% (w/w) P188 and protected with 8% (w/w) poly(ethylene glycol), was submitted to precooling at +10 °C for 1 h, freezing at -50 °C for 4 h, PD at +5 °C and 0.140 mbar for 24 h and a SD at +45 °C during 10 h. These conditions showed 188.4 ± 1.3 nm, 0.087 ± 0.014, 85.5 ± 1.4%, 0.61 ± 0.12%, -16.4 ± 0.1 mV and 325 ± 7 mOsm/kg of average size, polydispersity index, entrapment efficiency, residual moisture, surface charge and osmolality, respectively. It performed a long-term stability >12 months. DSC and XRD spectra confirmed adequate chemical interaction between formulation components and showed a semi-crystalline state after FD. CONCLUSIONS: An optimal freeze dried ocular formulation was achieved. Evidently, the successful design of this promising colloidal system resulted from rational cooperation between a good formulation and the right conditions in the FD process.

Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

Methoxy poly(ethylene oxide)-block-poly(ɛ-caprolactone) (PEO-b-PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Lysozyme-loaded lipid-polymer hybrid nanoparticles: preparation, characterization and colloidal stability evaluation.

CONTEXT: Lipid-polymer hybrid nanoparticles (LPNPs) are polymeric nanoparticles enveloped by lipid layers, which have emerged as a potent therapeutic nanocarrier alternative to liposomes and polymeric nanoparticles. OBJECTIVE: The aim of this work was to develop, characterize and evaluate LPNPs to deliver a model protein, lysozyme. MATERIALS AND METHODS: Lysozyme-loaded LPNPs were prepared by using the modified w/o/w double-emulsion-solvent-evaporation method. Poly-ɛ-caprolactone (PCL) was used as polymeric core material and tripalmitin:lechitin mixture was used to form a lipid shell around the LPNPs. LPNPs were evaluated for particle size distribution, zeta potential, morphology, encapsulation efficiency, in vitro drug release, stability and cytotoxicity. RESULTS: The DLS measurement results showed that the particle size of LPNPs ranged from 58.04 ± 1.95 nm to 2009.00 ± 0.52 nm. The AFM and TEM images of LPNPs demonstrate that LPNPs are spherical in shape. The protein-loading capacity of LPNPs ranged from 5.81% to 60.32%, depending on the formulation parameters. LPNPs displayed a biphasic drug release pattern with a burst release within 1 h, followed by sustained release afterward. Colloidal stability results of LPNPs in different media showed that particle size and zeta potential values of particles did not change significantly in all media except of FBS 100% for 120 h. Finally, the results of a cellular uptake study showed that LPNPs were significantly taken up by 83.3% in L929 cells. CONCLUSION: We concluded that the LPNPs prepared with PCL as polymeric core material and tripalmitin:lechitin mixture as lipid shell should be a promising choice for protein delivery.

Fabrication of uniform-sized poly-ɛ-caprolactone microspheres and their applications in human embryonic stem cell culture.

The generation of liquefied poly-ɛ-caprolactone (PCL) droplets by means of a microfluidic device results in uniform-sized microspheres, which are validated as microcarriers for human embryonic stem cell culture. Formed droplet size and size distribution, as well as the resulting PCL microsphere size, are correlated with the viscosity and flow rate ratio of the dispersed (Q d) and continuous (Q c) phases. PCL in dichloromethane increases its viscosity with concentration and molecular weight. Higher viscosity and Q d/Q c lead to the formation of larger droplets, within two observed formation modes: dripping and jetting. At low viscosity of dispersed phase and Q d/Q c, the microfluidic device is operated in dripping mode, which generates droplets and microspheres with greater size uniformity. Solutions with lower molecular weight PCL have lower viscosity, resulting in a wider concentration range for the dripping mode. When coated with extracellular matrix (ECM) proteins, the fabricated PCL microspheres are demonstrated capable of supporting the expansion of human embryonic stem cells.

Potential use of a bone tissue engineering scaffold based on electrospun poly (ɛ-caprolactone) - Poly (vinyl alcohol) hybrid nanofibers containing modified cockle shell nanopowder.

Today, the construction of scaffolds promoting the differentiation of stem cells is an intelligent innovation that accelerates the differentiation toward the target tissue. The use of calcium and phosphate compounds is capable of elevating the precision and efficiency of the osteogenic differentiation of stem cells. In this research, osteoconductive electrospun poly (ɛ-caprolactone) (PCL) - poly (vinyl alcohol) (PVA) hybrid nanofibrous scaffolds containing modified cockle shell (CS) nanopowder were prepared and investigated. In this regard, the modified CS nanopowder was prepared by grinding and modifying with phosphoric acid, and it was then added to PVA nanofibers at different weight percentages. Based on the SEM images, the optimum content of the modified CS nanopowder was set at 7 wt %, since reaching the threshold of agglomeration restricted this incorporation. In the second step, the PVA-CS7 nanofibrous sample was hybridized with different PCL ratios. Concerning the hydrophilicity and mechanical strength, the sample named PCL50-PVA50-CS7 was ultimately selected as the optimized and suitable candidate scaffold for bone tissue application. The accelerated hydrolytic degradation of the sample was also studied by FTIR and SEM analyses, and the results confirmed that the mineral deposits of CS are available approximately 7 days for mesenchymal stem cells. Moreover, Alizarin red staining illustrated that the presence of CS in the PCL50-PVA50-CS7 hybrid nanofibrous scaffold may potentially lead to an increase in calcium deposits with high precipitates, authenticating the differentiation of stem cells towards osteogenic cells.

Diabetic wound healing function of PCL/cellulose acetate nanofiber engineered with chitosan/cerium oxide nanoparticles.

The use of cerium oxide nanoparticles (CeO2NPs) in diabetic wound repair substances has shown promising results. Therefore, the study was conducted to introduce a novel nano-based wound dressing containing chitosan nanoparticles encapsulated with green synthesized cerium oxide nanoparticles using Thymus vulgaris extract (CeO2-CSNPs). The physical properties and structure of the nanoparticles were analyzed using XRD, DLS, FESEM and FTIR techniques. The electrospun PCL/cellulose acetate-based nanofiber was prepared and CeO2-CSNPs were integrated on the PCL/CA membrane by electrospraying. The physicochemical properties, morphology and biological characteristics of the electrospun nanocomposite were evaluated. The results showed that the nanocomposite with 0.1 % CeO2-CSNPs exhibited high antibacterial performance against S. aureus (<58.59 µg/mL). The PCL/CA/CeO2-CSNPs nanofiber showed significant antioxidant activity up to 89.59 %, cell viability improvement, and cell migration promotion up to 90.3 % after 48 h. The in vivo diabetic wound healing experiment revealed that PCL/CA/CeO2-CSNPs nanofibers can significantly increase the repair rate of diabetic wounds by up to 95.47 % after 15 days. The results of this research suggest that PCL/CA nanofiber mats functionalized with CeO2-CSNPs have the potential to be highly effective in treating diabetes-related wounds.

Synthesis and Properties of Modified Biodegradable Polymers Based on Caprolactone.

In this paper, the synthesis and characterization of two polycaprolactone-polydimethylsiloxane (PDMS-CL) copolymers with biodegradable properties are reported. A comparative study was carried out using an aminopropyl-terminated polydimethylsiloxane macro-initiator (APDMS) with two different molecular weights. The copolymers (PDMS-CL-1 and PDMS-CL-2) were obtained by ring-opening polymerization of ɛ-caprolactone using APDMS as initiators and stannous 2-ethylhexanoate as a catalyst. The copolymer's structures were confirmed by Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (1H-NMR) spectra, and energy dispersion spectroscopy (EDX). Surface morphology was investigated using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The hydrophobic properties of the copolymers were demonstrated by the water contact angle and water vapor sorption capacity. Additionally, biological tests were conducted on San Marzano type tomato plants (Lypercosium esculentum) to assess the synthesized copolymers' susceptibility to the environment in terms of biological stability and metabolic activity. The biodegradation of PDMS-CL-1 and PDMS-CL-2 copolymers does not have a dangerous effect on the metabolic activity of plants, which makes it a convenient product in interaction with the environment.

Dual-functionalized Pickering HIPE templated poly(ɛ-caprolactone) scaffold for maxillofacial implants.

High internal phase emulsion (HIPE) templated poly (ɛ-caprolactone) (PCL) scaffolds have gained widespread attention for large-sized bone defects due to its tuneable 3D architecture and ease of fabricating crosslinked PCL (cPCL) scaffolds. However, extremely high stabilizer (surfactant or nanoparticle) concentration and negligence of microenvironment for regeneration sites like alveolar bones have restrained industrial acceptance of these scaffolds. Herein, we demonstrated the fabrication of nanocomposite cPCL scaffolds within Pickering HIPE templates stabilized using modified silica nanoparticles (mSiNP) concentrations as low as 0.1 to 1.0 wt%. Using an unconventional approach, the mSiNP Pickering stabilizer was added in dispersed phase, contradicting Bancroft's rule. The colloidal stability was attained due to faster drifting of mSiNP towards the interface when it was dispersed in silicone oil. Scaffolds with tuneable properties were fabricated by controlling the mSiNP concentration and ϕd. Further, cPCL scaffolds were functionalized using clove oil (CO) to improve their efficiency in eradicating S. aureus and E. coli by disrupting their cellular integrity. Additionally, formation of biofilm on the surface of the scaffolds was successfully inhibited by the incorporation of CO. CO-functionalized scaffolds demonstrated excellent cytocompatibility towards MG-63 cells allowing their successful adhesion and proliferation on the surface of the scaffolds.

Chitosan-coated poly (Ɛ-caprolactone) nanoparticles as acaricide carriers.

Among many species of ticks that affect beef and dairy cattle, Rhipicephalus (Boophilus) microplus is the most common. It is responsible for heavy losses in milk and meat production. In this work we introduce nanostructures such as chitosan-poly-Ɛ-caprolactone (CS_PCL) nanoparticles to encapsulate amitraz (CS_PCLnp_Amitraz) and fluazuron (CS_PCLnp_Fluazuron) to treat tick infestations more effectively. The CS_PCLnp_Amitraz system has a final amitraz concentration of 1.0 mg/mL with a particle size of 275 ± 30 nm, surface charge of +43 ± 7 mV and entrapment efficiency of 77 ± 1%. The CS_PCLnp_Fluazuron system has a drug concentration of 0.5 mg/mL with a particle size of 295 ± 35 nm, surface charge of +45 ± 10 mV and entrapment efficiency of 89 ± 1%. Both systems reduced cytotoxicity on Balb/c 3T3 culture cells and were also active against R. microplus. Both molecules - amitraz and fluazuron - formed molecularly dispersed active compounds inside the core of the PCL polymer matrix. The PCL surface was composed of a chitosan layer, which influenced the stability of the steric nanoparticles at pH greater than 7. Both systems were stable at a saline concentration of 1.25 mol/L and at temperatures below 50 °C. Experiments conducted in vivo with CS_PCLnp_Amitraz, at doses of active ingredient equivalent to those of commercial products, showed decreased tick infestation for 21 days, as well as higher acaricide effect than observed for commercial products, which recommend a reapplication in 14 days. The acaricide effect was even stronger when CS_PCLnp_Amitraz (same dose as for commercial products) and CS_PCLnp_Fluazuron (half of the amount for commercial products) were administered together.

Preparation of a sustainable bio-copolymer based on Luffa cylindrica cellulose and poly(ɛ-caprolactone) for bioplastic applications.

In this research, a bio-based graft copolymer (LCC-g-PCL) based on the cellulose of Luffa cylindrica (LCC) main chain possessing poly(ɛ-caprolactone) (PCL) pendant groups is synthesized through a grafting from approach via ring-opening polymerization (ROP). For this purpose, LCC, extracted from luffa sponges by combined method, is utilized for ROP of ɛ-caprolactone (ɛ-CL) as a macro-initiator in the presence of stannous octoate as a catalyst. Fourier transform infrared (FT-IR), proton and carbon nuclear magnetic resonance (1H NMR and 13C NMR) spectroscopies are utilized to structurally indicate the success of ROP, while the achieved graft copolymer is analyzed in detail by comparing with LCC and neat PCL in terms of wettability, thermal and degradation behaviors by conducting water contact angle (WCA) measurements, thermogravimetric and differential scanning calorimetry analyses (TGA and DSC) and in vitro both hydrolytic and enzymatic biodegradation tests, respectively. The results of conducted tests show that the incorporation of PCL groups on LCC provide the increasing hydrophobicity. In addition, the degradation behavior of the LCC-g-PCL copolymer is found to be more pronounced under enzymatic medium rather than hydrolytic conditions. It is anticipated from the results that LCC-g-PCL can be a potential eco-friendly material particularly in bioplastic industry.

Electrospun Polycaprolactone (PCL)-Amnion Nanofibrous Membrane Promotes Nerve Regeneration and Prevents Fibrosis in a Rat Sciatic Nerve Transection Model.

Functional recovery after peripheral nerve injury repair is typically unsatisfactory. An anastomotically poor microenvironment and scarring at the repair site are important factors impeding nerve regeneration. In this study, an electrospun poly-e-caprolactone (PCL)-amnion nanofibrous membrane comprising an amnion membrane and nonwoven electrospun PCL was used to wrap the sciatic nerve repair site in the rat model of a sciatic nerve transection. The effect of the PCL-amnion nanofibrous membrane on improving nerve regeneration and preventing scarring at the repair site was evaluated by expression of the inflammatory cytokine, sciatic functional index (SFI), electrophysiology, and histological analyses. Four weeks after repair, the degree of nerve adhesion, collagen deposition, and intraneural macrophage invasion of the PCL-amnion nanofibrous membrane group were significantly decreased compared with those of the Control group. Moreover, the PCL-amnion nanofibrous membrane decreased the expression of pro-inflammatory cytokines such as interleukin(IL)-6, Tumor Necrosis Factor(TNF)-a and the number of pro-inflammatory M1 macrophages, and increased the expression of anti-inflammatory cytokine such as IL-10, IL-13 and anti-inflammatory M2 macrophages. At 16 weeks, the PCL-amnion nanofibrous membrane improved functional recovery, including promoting nerve Schwann cell proliferation, axon regeneration, and reducing the time of muscle denervation. In summary, the PCL-amnion nanofibrous membrane effectively improved nerve regeneration and prevent fibrosis after nerve repair, which has good clinical application prospect for tissue repair.

Polymeric Nanocapsules Containing Fennel Essential Oil: Their Preparation, Physicochemical Characterization, Stability over Time and in Simulated Gastrointestinal Conditions.

Plant essential oils, a source of biologically active compounds, represent a promising segment in the pharmaceutical market. However, their volatility, hydrophobicity, poor stability, and low toxicity limit direct use in pharmaceutical-related applications. Nanoencapsulation is a technique that allows overcoming these obstacles by improving bioaccessibility and bioavailability. Nanocapsules (NCs) based on biodegradable and biocompatible poly(ɛ-caprolactone) containing Foeniculum vulgare Mill. essential oil (FEO), known for its biological activities, were successfully prepared by interfacial deposition of the preformed polymer method. The composition of FEO (trans-anethole chemotype) was determined by gas chromatography analyses. The FEO presence inside the NCs was confirmed by nuclear magnetic resonance experiments. The FEO-NCs showed nanometer size (210 nm), low polydispersity index (0.10), negative zeta potential (-15 mV), non-Newtonian rheological behavior, and high efficiency of encapsulation (93%). Moreover, parameters such as FEO-NC particle size, bioactive compound retention, and FEO composition were monitored for 30 days at storage temperatures of 4 and 40 °C, confirming the robustness of the nanosystem. Finally, FEO-NCs were resistant to the simulated gastric digestion and showed an effective bioaccessibility of 29% in simulated intestinal digestion. Based on the results obtained, this FEO-NC nanosystem could find interesting applications in the nutraceutical and pharmaceutical sectors.

Blends Based on Poly(ε-Caprolactone) with Addition of Poly(Lactic Acid) and Coconut Fibers: Thermal Analysis, Ageing Behavior and Application for Embossing Process.

In this research a biodegradable blend of poly(ɛ-caprolactone) (PCL) and poly(lactic acid) (PLA) is proposed as a new material for the production of a relief printing plate used for special applications on packaging materials, i.e., the embossing process. Coconut fibers (CFs) were added as a natural filler to PCL/PLA blends to improve the functional properties of the prepared blends. Thermal, mechanical and surface analyses were performed on the unaged and artificially aged blends. The results showed that CF has been proven to optimize the hardness of the blend, which is crucial for the production of relief plate for embossing applications. The lowest hardness was measured on neat PCL (53.30° Sh D) and the highest value on PCL/PLA/CF 70/30/3.0 blend (60.13° Sh D). Stronger interfacial interactions were present at the PLA/CF interface because the interfacial free energy is closer to zero and the work of adhesion and spreading coefficient are higher than for the PCL/CF interface. The results of thermal analysis of unaged and aged blends showed that ageing for 3 weeks resulted in significantly lower thermal stability, especially for neat PCL and PCL/PLA 80/20 blends. Blends with a higher content of PLA and CF showed a slightly increased ageing resistance, which is attributed to the increased crystallinity of PLA after ageing due to the addition of CF showed in the DSC diagrams.