Poly(chitosan-ester-ether-urethane) Hydrogels as Highly Controlled Genistein Release Systems

Polymeric hydrogels play an increasingly important role in medicine, pharmacy and cosmetology. They appear to be one of the most promising groups of biomaterials due to their favorable physicochemical properties and biocompatibility. The objective of the presented study was to synthesize new poly(chitosan-ester-ether-urethane) hydrogels and to study the kinetic release of genistein (GEN) from these biomaterials. In view of the above, six non-toxic hydrogels were synthesized via the Ring-Opening Polymerization (ROP) and polyaddition processes. The poly(ester-ether) components of the hydrogels have been produced in the presence of the enzyme as a biocatalyst. In some cases, the in vitro release rate of GEN from the obtained hydrogels was characterized by near-zero-order kinetics, without “burst release” and with non-Fickian transport. It is important to note that developed hydrogels have been shown to possess the desired safety profile due to lack of cytotoxicity to skin cells (keratinocytes and fibroblasts). Taking into account the non-toxicity of hydrogels and the relatively highly controlled release profile of GEN, these results may provide fresh insight into polymeric hydrogels as an effective dermatological and/or cosmetological tool.     

Poly(ε‐caprolactone) composites containing gentamicin‐loaded β‐tricalcium phosphate/gelatin microspheres as bone tissue supports

In this work, novel antibacterial composites were prepared by using poly(ε‐caprolactone) (PCL) as the main matrix material, and gentamicin‐loaded microspheres composed of β‐tricalcium phosphate (β‐TCP) and gelatin. The purpose is to use this biodegradable material as a support for bone tissue. This composite system is expected to enhance bone regeneration by the presence of β‐TCP and prevent a possible infection that might occur around the defected bone region by the release of gentamicin. The effects of the ratio of the β‐TCP/gelatin microspheres on the morphological, mechanical, and degradation properties of composite films as well as in vitro antibiotic release and antibacterial activities against Escherichia coli and Staphylococcus aureus were investigated. The results showed that the composites of PCL and β‐TCP/gelatin microspheres had antibacterial activities for both bacteria. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Self-Assembled Nanoparticles Based on Block-Copolymers of Poly(2-Deoxy-2-methacrylamido-d-glucose)/Poly(N-Vinyl Succinamic Acid) with Poly(O-Cholesteryl Methacrylate) for Delivery of Hydrophobic Drugs

The self-assembly of amphiphilic block-copolymers is a convenient way to obtain soft nanomaterials of different morphology and scale. In turn, the use of a biomimetic approach makes it possible to synthesize polymers with fragments similar to natural macromolecules but more resistant to biodegradation. In this study, we synthesized the novel bio-inspired amphiphilic block-copolymers consisting of poly(N-methacrylamido-d-glucose) or poly(N-vinyl succinamic acid) as a hydrophilic fragment and poly(O-cholesteryl methacrylate) as a hydrophobic fragment. Block-copolymers were synthesized by radical addition–fragmentation chain-transfer (RAFT) polymerization using dithiobenzoate or trithiocarbonate chain-transfer agent depending on the first monomer, further forming the hydrophilic block. Both homopolymers and copolymers were characterized by ¹H NMR and Fourier transform infrared spectroscopy, as well as thermogravimetric analysis. The obtained copolymers had low dispersity (1.05–1.37) and molecular weights in the range of ~13,000–32,000. The amphiphilic copolymers demonstrated enhanced thermal stability in comparison with hydrophilic precursors. According to dynamic light scattering and nanoparticle tracking analysis, the obtained amphiphilic copolymers were able to self-assemble in aqueous media into nanoparticles with a hydrodynamic diameter of approximately 200 nm. An investigation of nanoparticles by transmission electron microscopy revealed their spherical shape. The obtained nanoparticles did not demonstrate cytotoxicity against human embryonic kidney (HEK293) and bronchial epithelial (BEAS-2B) cells, and they were characterized by a low uptake by macrophages in vitro. Paclitaxel loaded into the developed polymer nanoparticles retained biological activity against lung adenocarcinoma epithelial cells (A549).     

Poly(ε‐caprolactone) composite scaffolds loaded with gentamicin‐containing β‐tricalcium phosphate/gelatin microspheres for bone tissue engineering applications

In this study, novel poly(ε‐caprolactone) (PCL) composite scaffolds were prepared for bone tissue engineering applications, where gentamicin‐loaded β‐tricalcium phosphate (β‐TCP)/gelatin microspheres were added to PCL. The effects of the amount of β‐TCP/gelatin microspheres added to the PCL scaffold on various properties, such as the gentamicin release rate, biodegradability, morphology, mechanical strength, and pore size distribution, were investigated. A higher amount of filler caused a reduction in the mechanical properties and an increase in the pore size and led to a faster release of gentamicin. Human osteosarcoma cells (Saos‐2) were seeded on the prepared composite scaffolds, and the viability of cells having alkaline phosphatase (ALP) activity was observed for all of the scaffolds after 3 weeks of incubation. Cell proliferation and differentiation enhanced the mechanical strength of the scaffolds. Promising results were obtained for the development of bone cells on the prepared biocompatible, biodegradable, and antimicrobial composite scaffolds. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40110.     

Injectable gel: Poly(ethylene glycol)-sebacic acid polyester

In order to develop an injectable material for drug delivery that has both formulation advantages of a sol-to-gel transition system and minimal burst release of a drug, a soft thermogel of poly(ethylene glycol)-sebacic acid polyester was synthesized. The polymer aqueous solution (25 wt%) undergoes ‘clear sol-to-gel’ transition as the temperature increases from 5 to 65 °C. The drug can be mixed in a low viscous sol state at low temperature (<15 °C). In particular, the thermogel is soft enough to be injected through a 21-gauge syringe needle even as a gel state. The model hydrophilic drug, FITC-dextran (molecular weight: 40,000 Da), was released from the gel over 24 h. The biodegradable poly(ethylene glycol)-sebacic acid polyester soft thermogel is believed to be promising for the hydrophilic drug delivery where an initial burst of a drug might be a concern.     

Novel Silver-Functionalized Poly(ε-Caprolactone)/Biphasic Calcium Phosphate Scaffolds Designed to Counteract Post-Surgical Infections in Orthopedic Applications

In this study, we designed and developed novel poly(ε-caprolactone) (PCL)-based biomaterials, for use as bone scaffolds, through modification with both biphasic calcium phosphate (BCP), to impart bioactive/bioresorbable properties, and with silver nitrate, to provide antibacterial protection against Staphylococcus aureus, a microorganism involved in prosthetic joint infections (PJIs). Field emission scanning electron microscopy (FESEM) showed that the samples were characterized by square-shaped macropores, and energy dispersive X-ray spectroscopy analysis confirmed the presence of PCL and BCP phases, while inductively coupled plasma–mass spectrometry (ICP–MS) established the release of Ag⁺ in the medium (~0.15–0.8 wt% of initial Ag content). Adhesion assays revealed a significant (p < 0.0001) reduction in both adherent and planktonic staphylococci on the Ag-functionalized biomaterials, and the presence of an inhibition halo confirmed Ag release from enriched samples. To assess the potential outcome in promoting bone integration, preliminary tests on sarcoma osteogenic-2 (Saos-2) cells indicated PCL and BCP/PCL biocompatibility, but a reduction in viability was observed for Ag-added biomaterials. Due to their combined biodegrading and antimicrobial properties, the silver-enriched BCP/PCL-based scaffolds showed good potential for engineering of bone tissue and for reducing PJIs as a microbial anti-adhesive tool used in the delivery of targeted antimicrobial molecules, even if the amount of silver needs to be tuned to improve osteointegration.     

Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain

Background: Capsaicin, the hot pepper agent, produces burning followed by desensitization. To treat localized itch or pain with minimal burning, low capsaicin concentrations can be repeatedly applied. We hypothesized that alternatively controlled release of capsaicin from poly(lactic-co-glycolic acid) (PLGA) nanoparticles desensitizes superficially terminating nociceptors, reducing burning. Methods: Capsaicin-loaded PLGA nanoparticles were prepared (single-emulsion solvent evaporation) and characterized (size, morphology, capsaicin loading, encapsulation efficiency, in vitro release profile). Capsaicin-PLGA nanoparticles were applied to murine skin and evaluated in healthy human participants (n = 21) for 4 days under blinded conditions, and itch and nociceptive sensations evoked by mechanical, heat stimuli and pruritogens cowhage, β-alanine, BAM8-22 and histamine were evaluated. Results: Nanoparticles (loading: 58 µg capsaicin/mg) released in vitro 23% capsaicin within the first hour and had complete release at 72 h. In mice, 24 h post-application Capsaicin-PLGA nanoparticles penetrated the dermis and led to decreased nociceptive behavioral responses to heat and mechanical stimulation (desensitization). Application in humans produced a weak to moderate burning, dissipating after 3 h. A loss of heat pain up to 2 weeks was observed. After capsaicin nanoparticles, itch and nociceptive sensations were reduced in response to pruritogens cowhage, β-alanine or BAM8-22, but were normal to histamine. Conclusions: Capsaicin nanoparticles could be useful in reducing pain and itch associated with pruritic diseases that are histamine-independent.     

复合型阻燃剂对聚氯乙烯的阻燃抑烟作用研究

采用微胶囊红磷（MRP）、硼酸锌（ZnBO3）、氢氧化铝(ATH)和氢氧化镁(MH)进行复配对软质聚氯乙烯（PVC）进行阻燃处理,通过极限氧指数、热失重、锥形量热方法研究了不同配比阻燃剂对PVC的阻燃抑烟性能的影响。结果表明,当PVC/MRP/ZnBO3/ATH/MH质量比为100:3:1:20:20时,具有良好的阻燃抑烟效果,极限氧指数可达35.9 %;阻燃体系PVC/ATH/MH、PVC/MRP/ZnBO3/ATH/MH相对于纯PVC具有良好的阻燃抑烟性,PVC/MRP/ZnBO3/ATH/MH比PVC/ATH/MH体系在热释放、烟气、一氧化碳和二氧化碳排放指标上数值更低,热稳定性增加,成炭率更高,火灾性能指数提高,火灾蔓延指数减小,火灾危险性降低。     

Poly(2-hydroxyethylmethacrylate-co-2-folate ethylmethacrylate) and Folic acid/Poly(2-hydroxyethylmethacrylate) Solid Solution: Preparation and Drug Release Investigation

Poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) was synthesized by free radical polymerization of 2-hydroxyethylmethacrylate with 2-folatethylmethacrylate and folic acid/poly(2-hydroxyethylmethacrylate) solid solutions was prepared by mixing folic acid with poly(2-hydroxyethylmethacrylate) using the solution casting method. The structure and the homogeneity distribution of folic acid in the polymer matrix are characterized by different methods. The diffusion behaviors of water and folic acid through poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) and poly(2-hydroxyethylmethacrylate) matrixes were found obey to the Fick models. The in vitro cytotoxicity assessed by microculture tetrazolium test assay and the antioxidant activity of poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) systems determined by 1,1-diphenyl-2-picryl-hydrazyl method revealed no significant toxicity of these systems and has excellent free radical scavenger property which can be as safe candidate in drug-carrier system. The solubility enhancement of folic acid in different pH media is also investigated and the results obtained reveal a maximum of 399–400?mg?L^?1. The release dynamic of folic acid from the poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) containing 5?mol% of folic acid and that from folic acid/poly(2-hydroxyethylmethacrylate) system containing 10?mol% of folic acid have the best intestine/stomach ratio.     

The Pharmacokinetics and Pharmacodynamics of Lidocaine-Loaded Biodegradable Poly(lactic-co-glycolic acid) Microspheres

The purpose of this study was to develop novel lidocaine microspheres. Microspheres were prepared by the oil-in-water (o/w) emulsion technique using poly(d,l-lactide-co-glycolide acid) (PLGA) for the controlled delivery of lidocaine. The average diameter of lidocaine PLGA microspheres was 2.34 ± 0.3 μm. The poly disperse index was 0.21 ± 0.03, and the zeta potential was +0.34 ± 0.02 mV. The encapsulation efficiency and drug loading of the prepared microspheres were 90.5% ± 4.3% and 11.2% ± 1.4%. In vitro release indicated that the lidocaine microspheres had a well-sustained release efficacy, and in vivo studies showed that the area under the curve of lidocaine in microspheres was 2.02–2.06-fold that of lidocaine injection (p < 0.05). The pharmacodynamics results showed that lidocaine microspheres showed a significant release effect in rats, that the process to achieve efficacy was calm and lasting and that the analgesic effect had a significant dose-dependency.     

Hydrogels of modified ethylenediaminetetraacetic dianhydride gelatin conjugated with poly(ethylene glycol) dialdehyde as a drug‐release matrix

Hydrogels have been recognized as versatile biomaterials in biomedical applications. This article describes the synthesis and characterization of a poly(ethylene glycol) (PEG) dialdehyde derivative, the modification of gelatin with ethylenediaminetetraacetic dianhydride (EDTAD), and the conjugation of PEG dialdehyde for enhanced hydrophilicity, biocompatibility, and flexibility. Hydrogels of gelatin conjugated with various percentages of PEG dialdehyde (10–30%), 35% EDTAD‐modified gelatin, and 12% PEG dialdehyde conjugated with 31% EDTAD‐modified gelatin with or without 1% chlorhexidine were prepared. For all the synthesized gel formulations, the swelling kinetics and drug release in pH 7.4 and pH 4.5 buffers at 37°C were studied. Gels of PEG‐conjugated gelatin, 35% EDTAD‐modified gelatin, and 12% PEG conjugated with 31% EDTAD‐modified gelatin, with or without 1% chlorhexidine, showed significantly improved swelling ratios in comparison with gelatin. The drug release was unaffected by an increase in the percentage of PEG conjugation with gelatin. Complete drug release was recorded within 48 h in the pH 4.5 buffer, whereas in the pH 7.4 buffer, the drug release was accomplished within 128 h. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 1059–1067, 2004     

Comparison of poly(aspartic acid) hydrogel and poly(aspartic acid)/gelatin complex for entrapment and pH‐sensitive release of protein drugs

Biodegradable poly(aspartic acid) (PASP) hydrogel and PASP/gelatin complex were prepared to evaluate their potential application as pH‐sensitive matrices for controlled protein release. Entrapment of myoglobin (Mb) and its release were compared between the two types of carriers. It was found that incorporation of Mb into PASP hydrogel strongly depended on the medium pH and NaCl concentration, and was time‐consuming. However, complete entrapment of Mb into PASP/gelatin complex was found within pH ranged from 2.5 to 4.0, which was concomitant with the formation of PASP/gelatin complex. By adjusting Mb feed ratio, Mb entrapment in the complex can be up to 31.54% (by weight) with high loading efficiency (96.2%). Gradual release of Mb from PASP hydrogel was observed within pH 2.0–7.4, while Mb release from PASP/gelatin complex was negligible within pH 2.0–4.2 for 4 days. In addition, pulsatile Mb release can be achieved by combining polyanhydride with pH‐sensitive PASP/gelatin complex, while the device composed of polyanhydride and PASP hydrogel is mechanically unstable. PASP/gelatin complex formed by electrostatic interactions is superior to the single‐component PASP hydrogel synthesized by chemical cross‐linking as pH‐sensitive matrices for controlled protein release when entrapment of proteins and pH‐sensitivity of protein release are concerned. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

PLA Microspheres-Embedded PVA Hydrogels Prepared by Gamma-Irradiation and Freeze-Thaw Methods as Drug Release Carriers

A drug delivery system based on poly (vinyl alcohol) (PVA) hydrogels containing ibuprofen-loaded poly (lactic acid) (PLA) microspheres was developed to improve the release kinetics of this model drug. Gamma-irradiation and freeze-thawing were applied to prepare poly (vinyl alcohol) hydrogels. Properties and morphology of these composite hydrogels were investigated using FTIR, DSC, and SEM. In vitro release indicated that entrapment of the microspheres into the PVA hydrogels causes a reduction in both the release rate and the initial burst effect. PLA microspheres entrapped into the PVA hydrogels showed more suitable controlled release kinetics for drug delivery.     

Synthesis,Characterization, and Viscoelastic Behavior of Thermothickening Poly (N-Isopropylacrylamide-Methacrylicacide-Vinylpyrrolidone) Nanogels as an Injectable Biocompatible Drug Carrier

In the present work, the preparation of dual thermo-/pH-responsive nanogels composed poly (NIPAAm-MAA-VP) was investigated as an injectable carrier in which doxorubicin hydrochloride (DOX) was opted as an anticancer agent. The SEM photomicrographs showed that copolymer was almost spherical in shape with the mean diameter below 30 nm. Using dynamic oscillatory the gel-like behavior was observed at 37°C for the crosslinked polymer. Biocompatibility of the synthesized nanoparticles and superior antitumor activity of DOX-loaded nanoparticles were proved by in vitro cytotoxicity assay. The system is expected to be valuable for the delivery of chemotherapeutic agents in the treatment of solid tumors.     

Preparation of magnetic poly(lactic‐co‐glycolic acid) microspheres featuring monodispersity and controllable particle size using a microchannel device

Poly(lactic‐co‐glycolic acid) (PLGA) microspheres prepared using a traditional solvent evaporation or double emulsification method are usually polydisperse with an uncontrollable particle size distribution, which brings about poor application performance. In our research, monodisperse magnetic PLGA microspheres were prepared using a microchannel device based on a water‐in‐oil‐in‐water composite emulsion. The composite emulsion was formed by injecting a dichloromethane–gelatin water‐in‐oil emulsion into a microchannel together with an external water phase, i.e. poly(vinyl alcohol) (PVA) aqueous solution. Mean particle size control of the microspheres was executed using the osmotic pressure difference between internal and external aqueous phases caused by regulating NaCl concentration in PVA aqueous phase. It is found that monodisperse magnetic PLGA microspheres with high magnetic responsiveness can be successfully prepared combining the microchannel device with composite emulsion method. Mean particle size of the microspheres with coefficient of variation value below 4.72% is controllable from 123 to 203 µm depending on the osmotic pressure. The resulting samples have pyknotic and smooth surfaces, as well as spherical appearance. These monodisperse magnetic PLGA microspheres with good superparamagnetism and magnetic mobility have potential use as drug carriers for uniform release and magnetic targeting hyperthermia in biological fields. © 2015 Society of Chemical Industry     

Optical Properties of Composites Based on Poly(o-phenylenediamine), Poly(vinylenefluoride) and Double-Wall Carbon Nanotubes

In this work, synthesis and optical properties of a new composite based on poly(o-phenylenediamine) (POPD) fiber like structures, poly(vinylidene fluoride) (PVDF) spheres and double-walled carbon nanotubes (DWNTs) are reported. As increasing the PVDF weight in the mixture of the chemical polymerization reaction of o-phenylenediamine, the presence of the PVDF spheres onto the POPD fibers surface is highlighted by scanning electron microscopy (SEM). The down-shift of the Raman line from 1421 cm⁻¹ to 1415 cm⁻¹ proves the covalent functionalization of DWNTs with the POPD-PVDF blends. The changes in the absorbance of the IR bands peaked around 840, 881, 1240 and 1402 cm⁻¹ indicate hindrance steric effects induced of DWNTs to the POPD fiber like structures and the PVDF spheres, as a consequence of the functionalization process of carbon nanotubes with macromolecular compounds. The presence of the PVDF spheres onto the POPD fiber like structures surface induces a POPD photoluminescence (PL) quenching process. An additional PL quenching process of the POPD-PVDF blends is reported to be induced in the presence of DWNTs. The studies of anisotropic PL highlight a change of the angle of the binding of the PVDF spheres onto the POPD fiber like structures surface from 50.2° to 38° when the carbon nanotubes concentration increases in the POPD-PVDF/DWNTs composites mass up to 2 wt.%.     

Fabrication and characterization of dual drug-loaded poly (lactic-co-glycolic acid) fiber-microsphere composite scaffolds

The purpose of this work is to develop dual drug-loaded poly (lactic-co-glycolic acid) (PLGA) fiber-microsphere composite scaffolds with desired morphologies and dual drug loading properties, and to investigate the release kinetics of the dual drugs, both hydrophobic and hydrophilic, from the composite scaffolds. In this study, simvastatin (SIM) and bovine serum albumin (BSA) were used as model drugs, which were incorporated into the composite scaffolds by performing electrospinning and emulsion electrospraying simultaneously. The optimum condition for electrospraying (solution concentration: 0.06?g/mL; applied voltage: 15?kV; and flow rate: 0.6?mL/h) has been obtained to prepare PLGA microspheres. The release rate of SIM and BSA from the composite scaffolds fit the first order kinetics and the Higuchi model, respectively. The results indicated that fiber-microsphere composite scaffolds had the ability to load two types of drug, suggesting the scaffolds have great potential in the field of tissue engineering and combined therapies.     

Poly(alkylene sebacate ether)urethane hydrogels for indomethacin delivery formulations

A series of aliphatic polyurethane hydrogels based on poly(alkylene sebacate) diols was developed by polyaddition reaction. The chemical structures of unloaded and indomethacin-loaded poly(alkylene sebacate ether)urethane hydrogels were characterized using ATR-FT-IR spectroscopy. The aim of this research was to study the influence of the long alkylene chains on the indomethacin release rate. The swelling kinetics was analyzed using power law and second-order equation and it was found that both diffusion and polymer relaxation mechanisms control the overall rate of water uptake. The release mechanism follows the same behavior as swelling, but the interaction of the drug with the hydrophobic matrix influences the release kinetics. The surface properties and the influence of the surface configuration on the indomethacin release kinetics were also investigated using contact angle measurements. The mechanical properties of the dry samples were affected by the crosslinker, while, for the swollen samples, the stress–strain curves were overlapping and the mechanical parameter values decrease. The swelling of these hydrogels was also attributed to the network porosity, which was revealed by scanning electron microscopy (SEM) on freeze-dried specimens. The results prove the importance of the polyurethane matrix structure in the development of new drug releasing systems.