Microinjection Molded Biopolymeric Airway Stent with Antibacterial and Anti-Hyperplastic Properties

Central airway stenosis is a condition that the diameter of the trachea or main bronchus shrinkage is caused by external compression or internal tissue hyperplasia, which can cause difficulty breathing, asphyxia, and even death. Airway stenting is an easy way to restore the patency of the central airway, but airway stents commonly used in clinical practice can lead to complications such as mucus plugging, bacterial infection, and granulation tissue hyperplasia. Moreover, the non-degradable characteristic makes it requires a second operation to remove, which has the potential to cause tissue damage. In this study, a biodegradable airway stent is fabricated by microinjection molding using the bioelastomer of poly (L-lactide-co-ε-caprolactone) as the matrix material. The airway stent has excellent mechanical properties and an appropriate degradation rate. The hydrophilic surface of the airway stent can inhibit mucus plugging. The loading of silver nanoparticles and cisplatin endows the stent with antibacterial and anti-hyperplastic functions. In vitro and in vivo experiments demonstrate that this study provides an antibacterial and anti-hyperplastic biodegradable airway stent with elastic properties to avoid secondary removal operation and reduce complications associated with mucus plugging, bacterial infection, and granulation tissue hyperplasia.     

Preparation,Characterization and Drug Release Behavior of 5-Fluorouracil Loaded Carboxylic Poly(ε-caprolactone) Nanoparticles

In this paper, 5-Fluorouracil (5-FU) loaded carboxylic poly(ε-caprolactone) nanoparticles have been prepared by emulsification/solvent evaporation o/w method, and the drug release behaviors of 5-FU were investigated. The novel carboxylic poly (ε-caprolactone) (P(CL-OPD)-mal) was synthesized via conjugation of maleic anhydride to sodium borohydride (NaBH₄) reduced poly(ε-caprolactone-co -4- carbonyl -ε-caprolactone) (P(CL-OPD)), while P(CL-OPD) was synthesized in bulk by ring-opening polymerization of ε-caprolactone and 4-carbonyl-ε-caprolactone (OPD) with stannous octoate as a catalyst. Their structures were confirmed by ¹HNMR, FT-IR and GPC. Dynamic light scattering (DLS), transmission electron microscopy (TEM), zeta potential measurements were used for nanoparticle characterization. TEM and DLS showed the nanoparticles were with spherical shape and uniform size distribution (mean diameter 70～100 nm), respectively. Zeta potential analysis revealed that the nanoparticles had an increased negative surface with the increase of carboxyl group concentration. UV spectroscopy was adopted to study the entrapment and release behaviour. The maximum 5-FU loading efficiency was 14.39% with the entrapment efficiency be 42%. In vitro release studies were performed in PBS at 37°C. Results of the study showed that the release behavior can be well-controlled, and the balanced release was up to 96 h. P(CL-OPD)-mal nanoparticles would provide increased benefit in biomedical and pharmaceutical applications.     

Structural organization of plasma membrane lipids isolated from cells cultured as a monolayer and in tissue-like conditions

In this paper, folate conjugated poly(ε-caprolactone-co-4-maleate-ε-caprolactone) (P(CL-co-MCL)-folate) was prepared by a carbodiimide coupling reaction, i.e., the vitamin folic acid (FA) was covalently linked to the main chain of the maleate-functionalized polymer, poly(ε-caprolactone-co-4-maleate-ε-caprolactone) (P(CL-co-MCL)). Then the 5-Fluorouracil (5-FU) loaded nanoparticles of P(CL-co-MCL)-folate were achieved by solvent-evaporation method. Their properties were extensively studied by dynamic light scattering (DLS) and scan electron microscopy (SEM). DLS and SEM showed that the nanoparticles were in a well-defined spherical shape with a uniform size distribution. We also investigated the entrapment and in vitro release behavior, which indicated that the release speed of 5-FU could be well controlled and the release half-life period could reach 16.86h, which was 26.4 times longer than that of pure 5-FU. The in vitro targeting test displayed that the 5-FU loaded P(CL-co-MCL)-folate nanoparticles exhibited an enhanced cell inhibition because folate targeting increased the concentration of 5-FU loaded P(CL-co-MCL)-folate nanoparticles in the tumor cells with folate receptor overexpressed. Meanwhile, the tumor inhibition of 5-FU loaded P(CL-co-MCL)-folate nanoparticles was much higher than that of pure 5-FU and that of 5-FU loaded P(CL-co-MCL) nanoparticles. Therefore, P(CL-co-MCL)-folate nanoparticles would be highly beneficial for biomedical and pharmaceutical applications.     

Diselenide-containing poly(ε-caprolactone)-based thermo-responsive hydrogels with oxidation and reduction-triggered degradation

Herein, novel multi-responsive injectable polyester hydrogels were reported based on the diselenide-containing poly(ε-caprolactone) copolymers ((mPEG-PCL-Se)₂). The (mPEG-PCL-Se)₂ solution remained a free-flowing state at ambient temperature but spontaneously turned into a semisolid hydrogel upon heating to physiologic temperature. The phase transition temperature was examined to be dependent on the composition and aqueous concentration of the copolymers. More importantly, the thermo-responsive hydrogels were endowed with oxidation and reduction-triggered degradation by the incorporation of diselenide groups. Accordingly, the degradation of poly(ε-caprolactone)-based hydrogels was greatly improved and the rate of degradation was well regulated by the concentration of hydrogen peroxide (H₂O₂) or glutathione (GSH). This superior stimuli-responsive degradation could lead to an enhanced drug release of encapsulated drug (Doxorubicin, DOX). Thus the oxidation and reduction-triggered degradable diselenide-containing poly(ε-caprolactone) hydrogels would offer great potential for the controlled drug delivery.     

Lactone polymers. I. Glass transition temperature of poly-ε-caprolactone by means on compatible polymer mixtures

Dynamic mechanical properties determined with a torsion pendulum were used to ascertain the glass transition temperature T_g of poly-ε-caprolactone. By measurements on compatible blends of poly-ε-caprolactone and poly(vinyl chloride), the T_g of amorphous poly-ε-caprolactone was shown to be 202°K at about 1 cps. This is 16°K lower than the T_g of annealed, crystalline polymer. The blend transition data were well fitted by both the Fox and the Gordon-Taylor expressions. The Fox expression was also used to describe the decrease from 233°K of the secondary low-temperature relaxation due to poly(vinyl chloride) by assuming the low temperature relaxation of poly-ε-caprolactone, 138°K, was responsible for the decrease in the blends. The 138°K relaxation due to poly-ε-caprolactone was decreased when more than 50% poly(vinyl chloride) was present.     

Fabrication of biofunctional complex micelles with tunable structure for application in controlled drug release

In acidic solution, complex micelles were formed by diblock copolymers of poly (ethylene glycol)-b-poly (ε-caprolactone) (PEG-b-PCL) and folate-poly (2-(dimethylamino) ethyl methylacrylate)-b-poly (ε-caprolactone) (Fol-PDMAEMA-b-PCL) with a PCL core, a mixed PEG/Fol-PDMAEMA shell. The surface charge of the complex micelles was positive at acidic surroundings for the protonated PDMAEMA. With increasing pH value to 7.4 (above pK _a of PDMAEMA), these micelles could convert into a core-shell-corona (CSC) structure composing a hydrophobic PCL core, a collapsed PDMAEMA shell, and a soluble PEG corona. Compared to core-shell micelles formed by PEG-b-PCL, micelles with CSC structure can prolong degradation by enzyme. Doxorubicin was physically loaded into the PCL core. The drug release rate was pH-dependent. At pH 5.5, complex micelles with core-shell structure showed faster drug release rate, while at pH 7.4, complex micelles gained CSC structure which control the drug release at a lower rate. The multifunctional complex micelles were prepared for enhanced tumor therapy.     

New organic-inorganic nanohybrids via ring opening polymerization of (di)lactones initiated by functionalized polyhedral oligomeric silsesquioxane

The synthesis of new organic-inorganic materials were investigated. Poly(ε-caprolactone) and poly(l, l-lactide) covalently end-capped by a polyhedral oligomeric silsesquioxane (POSS) moiety, leading to new nanohybrid materials, were successfully prepared by coordination-insertion ring opening polymerization (ROP) of ε-caprolactone (ε-CL) and l,l-lactide (l,l-LA) respectively. The reaction was initiated from the primary amine available on aminopropylheptakis(isobutyl)POSS nanoparticles and catalyzed by tin(II) 2-ethylhexanoate (tin octoate, Sn(oct)₂). The covalent grafting of the polyester chains onto the POSS “nanocages” was assessed by selective fractionation experiment, Fourier transform infrared spectroscopy (FTIR) and further confirmed by proton nuclear magnetic resonance (¹H NMR). The polymerization proved to be well controlled as attested by the quite narrow polydispersity indices as determined by size exclusion chromatography (SEC). Furthermore, well-defined semi-crystalline poly(ε-caprolactone)-b-polylactide block copolymer carrying such POSS nanoparticle at one end was successfully synthesized attesting for the very efficient control over the polymerization reaction.     

In situ fabrication of paclitaxel‐loaded core‐crosslinked micelles via thiol‐ene “click” chemistry for reduction‐responsive drug release

In this study, a facile method to fabricate reduction‐responsive core‐crosslinked micelles via in situ thiol‐ene “click” reaction was reported. A series of biodegradable poly(ether‐ester)s with multiple pendent mercapto groups were first synthesized by melt polycondensation of diol poly(ethylene glycol), 1,4‐butanediol, and mercaptosuccinic acid using scandium trifluoromethanesulfonate [Sc(OTf)₃] as the catalyst. Then paclitaxel (PTX)‐loaded core‐crosslinked (CCL) micelles were successfully prepared by in situ crosslinking hydrophobic polyester blocks in aqueous media via thiol‐ene “click” chemistry using 2,2′‐dithiodiethanol diacrylate as the crosslinker. These PTX‐loaded CCL micelles with disulfide bonds exhibited reduction‐responsive behaviors in the presence of dithiothreitol (DTT). The drug release profile of the PTX‐loaded CCL micelles revealed that only a small amount of loaded PTX was released slowly in phosphate buffer solution (PBS) without DTT, while quick release was observed in the presence of 10.0 mM DTT. Cell count kit (CCK‐8) assays revealed that the reduction‐sensitive PTX‐loaded CCL micelles showed high antitumor activity toward HeLa cells, which was significantly higher than that of reduction‐insensitive counterparts and free PTX. This kind of biodegradable and biocompatible CCL micelles could serve as a bioreducible nanocarrier for the controlled antitumor drug release. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 99–107     

RING-OPENING POLYMERIZATION OF ε-CAPROLACTONE BY LANTHANOCENE CATALYSIS*

Ring-opening polymerization of ε-caprolactone (CL) catalyzed bylanthanocenes, O(C_2H_4C_5H_3CH_3)_2YCl (Cat-YCl) and Me_2Si[(CH_3)_3SiC_5H_3]_2NdCl(Cat-NdCl) has been carried out for the first time. It has been found that both yttroceneand neodymocene are very efficient to catalyze the polymerization of CL, giving high molec-ular weight poly (ε-caprolactone) (PCL ). The effects of [cat] / [ε- CL] molar ratio, polymeriza-tion temperature and time, as well as solvents were investigated and polymerization tem-perature is found to be the most important factor affecting the polymerization. The bulkpolymerization gives higher molecular weight PCL and higher conversion than that in solu-tion polymerization. NaBPh_4 was found to promote the polymerization of ε-caprolactone,and thus to increase both the polymerization conversion and MW of poly (ε- caprolactone ).     

Synthesis and barrier properties of poly(ε-caprolactone)-layered silicate nanocomposites

A new polymer-ceramic nanocomposite has been synthesized consisting of well-dispersed, two-dimensional layers of an organically modified mica-type silicate (MTS) within a degradable poly(ε-caprolactone) matrix. A protonated amino acid derivative of MTS was used to promote delamination/dispersion of the host layers and initiate ring-opening polymerization of ε-caprolactone monomer, resulting in poly(ε-caprolactone) chains that are ionically bound to the silicate layers. The polymer chains can be released from the silicate surface by a reverse ion-exchange reaction and were shown to be spectroscopically similar to pure poly(ε-caprolactone). Thick films of the polymer nanocomposite exhibit a significant reduction in water vapor permeability that shows a linear dependence on silicate content. The permeability of nanocomposite containing as low as 4.8% silicate by volume was reduced by nearly an order of magnitude compared to pure poly(ε-caprolactone). © 1995 John Wiley & Sons, Inc.     

Thermodynamic study of poly(vinyl chloride)/polyester blends by inverse-phase gas chromatography at 120°C

Polymer/polymer interaction parameters χ′₂₃ have been measured at 120°C as a function of polymer concentration for six different poly(vinyl chloride)/linear aliphatic polyester blends. The technique used is inverse-phase gas chromatography with several molecular probes. The polymers investigated are poly(DL-lactide), poly(ethylene succinate), poly(ethylene adipate), poly(butylene adipate), poly(δ-valerolactone), poly(ε-caprolactone) and poly(hexamethylene sebacate). Probe/polymer interaction parameters χ₁₂ and polymer/polymer interaction parameters χ′₂₃ values are dependent upon the methylene to carbonyl ratio of the polyester, reaching a minimum for a value of 5, this ratio corresponding to poly(ε-caprolactone) blends. Results are interpreted in terms of pairwise interactions between carbonyl, methylene, and [CHCl] groups.     

Zein supports scaffolding capacity toward mammalian cells and bactericidal and antiadhesive properties on poly(ε-caprolactone)/zein electrospun fibers

Studies investigate the electrospinnability of poly(ε-caprolactone)/protein blends to produce fibers for tissue engineering applications. However, no reports show that zein can improve the scaffolding capacity toward stem cells and promote antiadhesive and bactericidal properties to the poly(ε-caprolactone)/zein fibers. We create fibers with average diameters ranging from 200 to 400 nm from the electrospinning of poly(ε-caprolactone)/protein mixtures. Poly(ε-caprolactone)/zein blends are electrospinnable at zein concentration between 20 and 40 wt% in a 70/30 formic acid/acetic acid mixture. Water contact angle measurements indicate that zein increases fiber hydrophilicity. The water contact angle decreases from 118° (pure poly(ε-caprolactone) fiber) to 73° for the scaffold containing 40 wt% zein. The zein (40 wt%) significantly increases Young's modulus from 260 MPa (pure poly(ε-caprolactone) fibers) to 980 MPa (poly(ε-caprolactone)/zein fibers) with no substantial influence on elongation at break (ε ≥ 125%) and tensile strength (≥0.040 MPa). The electrospun scaffolds containing zein also promote cell adhesion, proliferation, and spreading of adipose-derived human mesenchymal stem cells for at least 7 days of culture. The zein on poly(ε-caprolactone)/zein fibers can prevent the attachment and proliferation of Escherichia coli and Staphylococcus aureus. We propose these materials for wound healing and skin repair.     

Superhydrophobic materials for tunable drug release: using displacement of air to control delivery rates

We have prepared 3D superhydrophobic materials from biocompatible building blocks, where air acts as a barrier component in a porous electrospun mesh to control the rate at which drug is released. Specifically, we fabricated poly(ε-caprolactone) electrospun meshes containing poly(glycerol monostearate-co-ε-caprolactone) as a hydrophobic polymer dopant, which results in meshes with a high apparent contact angle. We demonstrate that the apparent contact angle of these meshes dictates the rate at which water penetrates into the porous network and displaces entrapped air. The addition of a model bioactive agent (SN-38) showed a release rate with a striking dependence on the apparent contact angle that can be explained by this displacement of air within the electrospun meshes. We further show that porous electrospun meshes with higher surface area can be prepared that release more slowly than control nonporous constructs. Finally, the entrapped air layer within superhydrophobic meshes is shown to be robust in the presence of serum, as drug-loaded meshes were efficacious against cancer cells in vitro for >60 days, thus demonstrating their applicability for long-term drug delivery.     

Poly(ethylene oxide)-block-poly(α-cinnamyl-ε-caprolactone-co-ε-caprolactone) diblock copolymer nanocarriers for enhanced solubilization of caffeic acid phenethyl ester

We report novel micellar carriers, comprising pendant cinnamyl moieties in the core-forming block, designed to increase the solubilization of caffeic acid phenethyl ester (CAPE) in aqueous media. Amphiphilic poly(ethylene oxide)-block-poly(α-cinnamyl-ε-caprolactone-co-ε-caprolactone) (PEO-b-P(CyCL-co-CL) diblock copolymers were synthesized by ring-opening copolymerization of α-propargyl-ε-caprolactone and ε-caprolactone from a monofunctional PEO macroinitiator and subsequent attachment of cinnamyl groups via click reaction. In addition, a linear PEO-b-PCL diblock copolymer was synthesized and used in this study for comparison. Next, nanosized micelles from PEO-b-P(CyCL-co-CL) and PEO-b-PCL were formed via the solvent evaporation method and then loaded with CAPE. Dynamic and electrophoretic light scattering, and transmission electron microscopy were used to characterize both blank and loaded carriers. The potential of the micelles comprising pendant cinnamyl group to solubilize CAPE in water was evaluated in a comparative fashion to that of nonmodified PEO-b-PCL diblock copolymer.     

富勒烯衍生物引发的富勒烯末端封端聚己内酯的合成

利用带活性羟基的N-取代3,4-富勒烯吡咯烷作为引发剂,引发ε-己内酯开环聚合,制备了一种具有新型结构的富勒烯末端封端聚己内酯,通过核磁共振(1H NMR,13C NMR)、红外光谱(FTIR)和基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)等手段对产物进行了结构表征,并用热重(TG)分析和差示扫描量热(DSC)分析的方法进行了热学性能分析.结果表明,与聚己内酯相比产物热稳定性增加.     

Fluorescent micelles based on star amphiphilic copolymer with a porphyrin core for bioimaging and drug delivery

Star-shaped poly(ε-caprolactone)-b-poly(ethylene oxide) amphiphilic copolymer with a tetrakis-(4-aminophenyl)-terminated porphyrin core was synthesized. Paclitaxel (PTX)-loaded polymeric micelles were prepared by the self-assembly of the star copolymer and in situ encapsulation of PTX. The fluorescent characteristic of the porphyrin moiety allowed the cellular uptake and biodistribution of the PTX-loaded micelles to be monitored by fluorescent imaging. The PTX-loaded micelles can be readily internalized by cancer cells and have a slightly higher cytotoxicity than clinic PTX injection Taxol. In vivo real-time fluorescent imaging revealed that the micelles could accumulate at tumor site via the blood circulation in tumor-bearing mice. In vivo antitumor efficacy examinations indicated that the PTX-loaded micelles had significantly superior efficacy in impeding tumor growth than Taxol and low toxicity to the living mice.     

Controlled-release and antibacterial studies of doxycycline-loaded poly(ε-caprolactone) microspheres

The objective of the present study is to achieve doxycycline’s maximum therapeutic efficacy. Doxycycline-loaded poly(ε-caprolactone) microspheres were prepared by water-in-oil-in-water (w/o/w) double emulsion solvent evaporation technique with different formulation variables such as concentrations of drug and polymer. The effects of these variables on surface morphology, particle size distribution, encapsulation efficiency, and in vitro release behavior were examined. To observe the nature of microspheres, X-ray diffraction studies were carried out. The release data obtained were determined using various kinetic models and Korsmeyer–Peppas model showed an acceptable regression value for all compositions. Antibacterial efficiency of doxycycline-loaded poly(ε-caprolactone) microspheres were assessed by determining Minimum Inhibition Concentration (MIC) by standard tube dilution method against four standard pathogenic strains. The in vitro drug release studies were carried out in phosphate buffer solution (pH 7.2). The results showed marked retardation of doxycycline release and higher percentage of polymer gave longer drug release profile. This may definitely provide a useful controlled-release drug therapy and also prove to be effective over a long period of time (76 h).     

Fabrication of PLCL Block Polymer with Tunable Structure and Properties for Biomedical Application

Biodegradable materials are pivotal in the biomedical field, where how to precisely control their structure and performance is critical for their translational application. In this study, poly(L-lactide-b-ε-caprolactone) block copolymers (bPLCL) with well-defined segment structure are obtained by a first synthesis of poly(ε-caprolactone) soft block, followed by ring opening polymerization of lactide to form poly(L-lactide acid)  hard block. The pre-polymerization allows for fabrication of bPLCL with the definite compositions of soft/hard segment while preserving the individual segment of their special soft or hard segment. These priorities make the bPLCL afford biodegradable polymer with better mechanical and biodegradable controllability than the random poly(L-lactide-co-ε-caprolactone) (rPLCL) synthesized via traditional one-pot polymerization. 10 mol% ε-caprolactone introduction can result in a formation of an elastic polymer with elongation at break of 286.15% ± 55.23%. Also, bPLCL preserves the unique crystalline structure of the soft and hard segments to present a more sustainable biodegradability than the rPLCL. The combinative merits make the pre-polymerization technique a promising strategy for a scalable production of PLCL materials for potential biomedical application.     

Water-dispersible Fe3O4 nanoparticles stabilized with a biodegradable amphiphilic copolymer

In this work, we report a green synthetic method using water-dispersible magnetite nanoparticles containing oleic acid and poly(2-ethyl-2-oxazoline)-poly(ɛ-caprolactone) diblock copolymer as the magnetite nanoparticle dispersants. The Fe₃O₄ nanoparticles were prepared by co-precipitation and had a bilayer surface with a hydrophobic inner poly(ɛ-caprolactone) (PCL) layer and hydrophilic corona poly(2-ethyl-2-oxazoline) (POX) blocks. Also, the role of the ultrasonicating treatment's duration on the percent of magnetite in the complex and on its magnetic properties was investigated. Transmission electron microscopy (TEM) showed the average particle size to be about 10–20 nm in diameter for nanoparticles.     

Preparation of poly(butylene-co-ε-caprolactone carbonate) and their use as drug carriers for a controlled delivery system

Poly(butylene-co-ε-caprolactone carbonate) (PBCCL) was successfully synthesized via terpolymerization of carbon dioxide, 1,2-butylene oxide (BO), and ε-caprolactone (ε-CL). ε-CL was inserted into the backbone of BO-CO₂. The glass transition temperature (T_g) and the decomposition temperature (T_d) of PBCCL were much higher than those of poly(butylene carbonate) (PBC). The degradation rate of PBCCL was higher than that of PBC in a pH 7.4 phosphate-buffered solution. ε-CL offered an ester structural unit that gave the terpolymers remarkable degradability. PBC and PBCCL microcapsules containing a hydrophilic antibiotic drug pazufloxacin mesilate (PZFX) were elaborated by solvent evaporation method based on the formation of double W/O/W emulsion. Microcapsules were characterized in terms of the morphology, size, amount of encapsulated, and encapsulation efficiency. The results showed that the microcapsules had smooth and spherical surfaces, and the mean diameter of the microcapsules was in the range of 0.5–1 μm. Of all, 87.90% drug encapsulation efficiency has been achieved for microcapsules of 38.21% drug loading. In vitro drug release of these microcapsules was performed in a pH 7.4 phosphate-buffered solution. The release profiles were investigated from the measurement of PZFX presented in the release medium at various intervals. The release profiles of PZFX from PBC and PBCL microcapsules were found to be biphasic with a burst release followed by a gradual release phase. The release rate of PZFX from the microcapsules increased with increasing the content of ε-CL inserted into the copolymers. It showed that the release profiles of PZFX were highly polymer-dependent. © 2007 Wiley Periodicals, Inc. JPolym Sci Part A: Polym Chem 45: 2152–2160, 2007