Polyurethane-biomacromolecule combined foam dressing containing asiaticoside: fabrication, characterization and clinical efficacy for traumatic dermal wound treatment.

Polyurethane combined (PUC) foam dressings with various biomacromolecules were fabricated with the adsorption of asiaticoside and silver nanoparticles for traumatic wound treatment. Biomacromolecules had varying effects on physicochemical and mechanical properties of PU foam. With 2% incorporation, starches, high molecular weight chitosan and gelatin provided stiffer and more porous foams while carboxymethylcellulose had the highest compression strength but the lowest water vapor transmission. High water absorption was from foams with carboxymethylcellulose, alginate, hydroxypropyl methylcellulose and low molecular weight chitosan. Increasing the concentrations up to 12% had more prominent effect. However, powdery surface was noticed with poorer tensile properties that 6% incorporation was selected. FTIR spectra and DSC thermograms suggested interaction of PU formulation with biomacromolecules. EDS analysis confirmed existence of active compounds while acceptable stability was from sterilized PUC foam with alginate. On healthy volunteers, this selected foam dressing caused no skin irritation and retained moisture comparable to commercial product. In patients with traumatic dermal wounds, healing improvement with shorter wound closure time, higher reepithelialization and less pain score were from the selected foam dressing compared to standard gauze soaked with chlorhexidine. This PU-alginate combined foam dressing adsorbed with asiaticoside and silver nanoparticles proved advantages for traumatic dermal wound management.

Synthesis of magnetic gold coated poly (ε-caprolactonediol) based polyurethane/poly(N-isopropylacrylamide)-grafted-chitosan core-shell nanofibers for controlled release of paclitaxel and 5-FU.

The poly (ε-caprolactonediol) based polyurethane (PCL-Diol-b-PU)/poly(N-isopropylacrylamide)-grafted-chitosan (PNIPAAm-g-chitosan) core-shell nanofibers were synthesized via coaxial electrospinning process. Paclitaxel and 5-FU anticancer drugs were incorporated into the core of nanofibers. The nanofibers surface was coated using magnetic gold nanoparticles and the potential of synthesized nanofibers was investigated for the sustained release of paclitaxel and 5-FU toward 4T1 breast cancer cells death in vitro and in vivo. The synthesized magnetic nanoparticles were characterized using SEM, TEM, XRD and DLS analysis. The surface morphology of nanofibers was studied under various applied voltage and different shell flow rates. The paclitaxel and 5-FU release profiles from nanofibers were examined under acidic and physiological pH. The maximum 4T1 cell killing was found to be 78% using magnetic gold coated-nanofibers in the presence of external magnetic field. The SEM images after incubation of nanofibers in 4T1 breast cancer cells indicated the well adhesion of cells on the nanofibers surface. The in vivo studies showed that the tumor volume did not change during 10 days. The minimum increase in tumor volume was obtained using paclitaxel and 5-FU loaded-nanofibers coated by the magnetic gold nanoparticles. The obtained results demonstrated the high therapeutic efficiency of synthesized nanofibrous carrier toward breast cancer treatment.

Early fragmentation of polyester urethane sheet neither causes persistent oxidative stress nor alters the outcome of normal tissue healing in rat skin.

Silicone breast implant is associated with complications inherent to the surgical procedure. Prosthesis coating with polyurethane, however, commonly reduces the incidence of such complications. In this paper, the authors evaluated the inflammatory histomorphometric profile and oxidative damage associated to the implant of polyester urethane sheets. Forty-eight Wistar rats were divided into Sham or polyester urethane groups (n = 8/group) and underwent a polyester urethane implant in the dorsal skinfold. Tissue samples were collected on days seven, 30, and 90 after surgery and subjected to histomorphometric analysis and biochemical tests. Results were analyzed by one-way ANOVA (p ≤ 0.05). Peri-implant tissue samples exhibited characteristic inflammatory response associated with the biomaterial, with increased vascularization on day seven and augmented levels of IL1-b and TNF-a after 30 days. Peri-implant fibrocystic population was small on day seven, but increased considerably after 90 days. A rise in the carbonyl group levels of skin samples in the polyester urethane group was observed on day seven. Findings suggest that polyester urethane sheets undergo biodegradation at an early stage after implantation, followed by increased vascularity and microencapsulation of biomaterial fragments, without persistent oxidative damage. Fiber arrangement inside the collagen matrix results in a fibrotic scar because of polyester urethane degradation.

Responsive antimicrobial dental adhesive based on drug-silica co-assembled particles.

Most dental resin composite restorations are replacements for failing restorations. Degradation of the restoration-tooth margins by cariogenic bacteria results in recurrent caries, a leading cause for restoration failure. Incorporating antimicrobial agents in dental adhesives could reduce interfacial bacterial count and reduce recurrent caries rates, inhibit interfacial degradation, and prolong restoration service life, while minimizing systemic exposure. Direct addition of antimicrobial compounds into restorative materials have limited release periods and could affect the integrity of the material. Attempts to incorporate antimicrobial within mesoporous silica nanoparticles showed theoretical promise due to their physical robustness and large available internal volume, yet yielded short-term burst release and limited therapeutic payload. We have developed novel broad-spectrum antimicrobial drug-silica particles co-assembled for long-term release and high payload incorporated into dental adhesives. The release of the drug, octenidine dihydrochloride, is modulated by the oral degradative environment and mathematically modeled to predict effective service life. Steady-state release kills cariogenic bacteria, preventing biofilm formation over the adhesive surface, with no toxicity. This novel material could extend dental restoration service life and may be applied to other long-term medical device-tissue interfaces for responsive drug release upon bacterial infection. STATEMENT OF SIGNIFICANCE: This study describes a novel dental adhesive that includes a broad-spectrum antimicrobial drug-silica co-assembled particles for long-term antimicrobial effect. The release of the drug, octenidine dihydrochloride, is modulated by the oral degradative environment and mathematically modeled to predict effective release throughout the service life of the restoration. Steady-state drug-release kills caries-forming bacteria, preventing biofilm formation over the adhesive surface, without toxicity. This novel material could extend dental restoration service life and may be applied to other long-term medical device-tissue interfaces for responsive drug release upon bacterial infection. Since recurrent cavities (caries) caused by bacteria are the major reason for dental filling failure, this development represents a significant contribution to the biomaterials field in methodology and material performance.

Simultaneous Improvement of Oxidative and Hydrolytic Resistance of Polycarbonate Urethanes Based on Polydimethylsiloxane/Poly(hexamethylene carbonate) Mixed Macrodiols.

The degradation behaviors including oxidation and hydrolysis of silicone modified polycarbonate urethanes were thoroughly investigated. These polyurethanes were based on polyhexamethylene carbonate (PHMC)/polydimethylsiloxane (PDMS) mixed macrodiols with molar ratio of PDMS ranging from 5% to 30%. It was proved that PDMS tended to migrate toward surface and even a small amount of PDMS could form a silicone-like surface. Macrophages-mediated oxidation process indicated that the PDMS surface layer was desirable to protect the fragile soft PHMC from the attack of degradative species. Hydrolysis process was probed in detail after immersing in boiling buffered water using combined analytical tools. Hydrolytically stable PDMS could act as protective shields for the bulk to hinder the chain scission of polycarbonate carbonyls whereas the hydrolysis of urethane linkages was less affected. Although the promoted phase separation at higher PDMS fractions lead to possible physical defects and mechanical compromise after degradation, simultaneously enhanced oxidation and hydrolysis resistance could be achieved for the polyurethanes with proper PDMS incorporation.

Multistimuli-Responsive Amphiphilic Poly(ester-urethane) Nanoassemblies Based on l-Tyrosine for Intracellular Drug Delivery to Cancer Cells.

Multistimuli-responsive l-tyrosine-based amphiphilic poly(ester-urethane) nanocarriers were designed and developed for the first time to administer anticancer drugs in cancer tissue environments via thermoresponsiveness and lysosomal enzymatic biodegradation from a single polymer platform. For this purpose, multifunctional l-tyrosine monomer was tailor-made with a PEGylated side chain at the phenolic position along with urethane and carboxylic ester functionalities. Under melt dual ester-urethane polycondensation, the tyrosine monomer reacted with diols to produce high molecular weight amphiphilic poly(ester-urethane)s. The polymers produced 100 ± 10 nm spherical nanoparticles in aqueous medium, and they exhibited thermoresponsiveness followed by phase transition from clear solution into a turbid solution in heating/cooling cycles. Variable temperature transmittance, dynamic light scattering, and 1H NMR studies revealed that the polymer chains underwent reversible phase transition from coil-to-expanded chain conformation for exhibiting the thermoresponsive behavior. The lower critical solution temperature of the nanocarriers was found to correspond to cancer tissue temperature (at 42-44 °C), which was explored as an extracellular trigger (stimuli-1) for drug delivery through the disassembly process. The ester bond in the poly(ester-urethane) backbones readily underwent enzymatic biodegradation in the lysosomal compartments that served as intracellular stimuli (stimuli-2) to deliver drugs. Doxorubicin (DOX) and camptothecin (CPT) drug-loaded polymer nanocarriers were tested for cellular uptake and cytotoxicity studies in the normal WT-MEF cell line and cervical (HeLa) and breast (MCF7) cancer cell lines. In vitro drug release studies revealed that the polymer nanoparticles were stable under physiological conditions (37 °C, pH 7.4) and they exclusively underwent disassembly at cancer tissue temperature (at 42 °C) and biodegradation by lysosomal-esterase enzyme to deliver 90% of DOX and CPT. Drug-loaded polymer nanoparticles exhibited better cytotoxic effects than their corresponding free drugs. Live cell confocal microscopy imaging experiments with lysosomal tracker confirmed the endocytosis of the polymer nanoparticles and their biodegradation in the lysosomal compartments in cancer cells. The increment in the drug content in the cells incubated at 42 °C compared to 37 °C supported the enhanced drug uptake by the cancer cells under thermoresponsive stimuli. The present work creates a new platform for the l-amino acid multiple-responsive polymer nanocarrier platform for drug delivery, and the proof-of-concept was successfully demonstrated for l-tyrosine polymers in cervical and breast cancer cells.

Fabrication and characterization of gefitinib-releasing polyurethane foam as a coating for drug-eluting stent in the treatment of bronchotracheal cancer.

The purpose of the present study was to develop gefitinib-loaded polymeric foams that can be used as coating of drug-eluting stents for palliative treatment of bronchotracheal cancer. Release of such an anticancer drug from such stent coating can retard tumor regrowth into the bronchial lumen. Gefitinib-loaded polyurethane (PU) foams were prepared by embedding either gefitinib micronized crystals or gefitinib-loaded poly(lactic-co-glycolic acid) microspheres in water-blown films, with up to 10% w/w loading for gefitinib microcrystals and 15% w/w for gefitinib microspheres (corresponding to 1.0% w/w drug loading). Drug-release studies showed sustained release of gefitinib over a period of nine months, with higher absolute release rates at higher drug loading content. By the end of the studied nine month release periods, 60-100% of the loaded gefitinib had been released. Foams loaded with gefitinib-PLGA microspheres at 15% w/w showed accelerated drug release after 4 months, coinciding with the degradation of PLGA microparticles in the PU foam as demonstrated by scanning electron microscopy (SEM). When applied on a nitinol braided bronchotrachial stent, PU coatings with gefitinib microspheres showed similar mechanical properties as the drug-free PU coating, which indicated that the loading of microspheres did not affect the mechnical properties of the PU foams. In conclusion, we have fabricated drug-loaded PU foams that are suitable for bronchotracheal stent coating.

A theranostic dental pulp capping agent with improved MRI and CT contrast and biological properties.

Different materials have been used for vital dental pulp treatment. Preferably a pulp capping agent should show appropriate biological performance, excellent handling properties, and a good imaging contrast. These features can be delivered into a single material through the combination of therapeutic and diagnostic agents (i.e. theranostic). Calcium phosphate based composites (CPCs) are potentially ideal candidate for pulp treatment, although poor imaging contrast and poor dentino-inductive properties are limiting their clinical use. In this study, a theranostic dental pulp capping agent was developed. First, imaging properties of the CPC were improved by using a core-shell structured dual contrast agent (csDCA) consisting of superparamagnetic iron oxide (SPIO) and colloidal gold, as MRI and CT contrast agent respectively. Second, biological properties were implemented by using a dentinogenic factor (i.e. bone morphogenetic protein 2, BMP-2). The obtained CPC/csDCA/BMP-2 composite was tested in vivo, as direct pulp capping agent, in a male Habsi goat incisor model. Our outcomes showed no relevant alteration of the handling and mechanical properties (e.g. setting time, injectability, and compressive strength) by the incorporation of csDCA particles. In vivo results proved MRI contrast enhancement up to 7weeks. Incisors treated with BMP-2 showed improved tertiary dentin deposition as well as faster cement degradation as measured by µCT assessment. In conclusion, the presented theranostic agent matches the imaging and regenerative requirements for pulp capping applications. STATEMENT OF SIGNIFICANCE: In this study, we combined diagnostic and therapeutic agents in order to developed a theranostic pulp capping agent with enhanced MRI and CT contrast and improved dentin regeneration ability. In our study we cover all the steps from material preparation, mechanical and in vitro characterization, to in vivo study in a goat dental model. To the best of our knowledge, this is the first time that a theranostic pulp capping material have been developed and tested in an in vivo animal model. Our promising results in term of imaging contrast enhancement and of induction of new dentin formation, open a new scenario in the development of innovative dental materials.

Hemocompatibility of Degrading Polymeric Biomaterials: Degradable Polar Hydrophobic Ionic Polyurethane versus Poly(lactic-co-glycolic) Acid.

The use of degradable polymers in vascular tissue regeneration has sparked the need to characterize polymer biocompatibility during degradation. While tissue compatibility has been frequently addressed, studies on polymer hemocompatibility during degradation are limited. The current study evaluated the differences in hemocompatibility (platelet response, complement activation, and coagulation cascade initiation) between as-made and hydrolyzed poly(lactic-co-glycolic) acid (PLGA) and degradable polar hydrophobic ionic polyurethane (D-PHI). Platelet activation decreased (in whole blood) and platelet adhesion decreased (in blood without leukocytes) for degraded versus as-made PLGA. D-PHI showed minimal hemocompatibility changes over degradation. Leukocytes played a major role in mediating platelet activation for samples and controls, as well as influencing platelet-polymer adhesion on the degraded materials. This study demonstrates the importance of assessing the blood compatibility of biomaterials over the course of degradation since the associated changes in surface chemistry and physical state could significantly change biomaterial hemocompatibility.

Shape memory polyurethanes with oxidation-induced degradation: In vivo and in vitro correlations for endovascular material applications.

The synthesis of thermoset shape memory polymer (SMP) polyurethanes from symmetric, aliphatic alcohols and diisocyanates has previously demonstrated excellent biocompatibility in short term in vitro and in vivo studies, although long term stability has not been investigated. Here we demonstrate that while rapid oxidation occurs in these thermoset SMPs, facilitated by the incorporation of multi-functional, branching amino groups, byproduct analysis does not indicate toxicological concern for these materials. Through complex multi-step chemical reactions, chain scission begins from the amines in the monomeric repeat units, and results, ultimately, in the formation of carboxylic acids, secondary and primary amines; the degradation rate and product concentrations were confirmed using liquid chromatography mass spectrometry, in model compound studies, yielding a previously unexamined degradation mechanism for these biomaterials. The rate of degradation is dependent on the hydrogen peroxide concentration, and comparison of explanted samples reveals a much slower rate in vivo compared to the widely accepted literature in vitro real-time equivalent of 3% H2O2. Cytotoxicity studies of the material surface, and examination of the degradation product accumulations, indicate that degradation has negligible impact on cytotoxicity of these materials. STATEMENT OF SIGNIFICANCE: This paper presents an in-depth analysis on the degradation of porous, shape memory polyurethanes (SMPs), including traditional surface characterization as well as model degradation compounds with absolute quantification. This combination of techniques allows for determination of rates of degradation as well as accumulation of individual degradation products. These behaviors are used for in vivo-in vitro comparisons for determination of real time degradation rates. Previous studies have primarily been limited to surface characterization without examination of degradation products and accumulation rates. To our knowledge, our work presents a unique example where a range of material scales (atomistic-scale model compounds along with macroscopic porous SMPs) are used in conjunction with ex planted samples for calculation of degradation rates and toxicological risk.

Biodegradable polyurethane micelles with pH and reduction responsive properties for intracellular drug delivery.

Polyurethane micelles with disulfide linkage located at the interface of hydrophilic shell and hydrophobic core (PU-SS-I) have been shown enhanced drug release profiles. However, the payloads could not be released completely. The occurrence of aggregation of hydrophobic cores upon shedding hydrophilic PEG coronas was considered as the reason for the incomplete release. To verify the above hypothesis and to develop a new polyurethane based micelles with dual stimuli respond properties and controllable location of pH and reduction responsive groups in the PU main chains, a tertiary amine was incorporated into the hydrophobic core PU-SS-I, which resulted polyurethane with both reduction and pH sensitive properties (PU-SS-N). Biodegradable polyurethane with only disulfide linkages located between the hydrophilic PEG segment and the hydrophobic PCL segments (PU-SS-I) and polyurethane with only pH sensitive tertiary amine at the hydrophobic core (PU-N-C) were used as comparisons. Paclitaxel (PTX) was chosen as mode hydrophobic drug to evaluate the loading and redox triggered release profiles of the PU micelles. It was demonstrated that PU-SS-N micelles disassembled instantly at the presence of 10mM GSH and at an acidic environment (pH=5.5), which resulted the nearly complete release (~90%) of the payloads within 48h, while about ~70% PTX was released from PU-SS-I and PU-SS-N micelles at neutral environment (pH=7.4) with the presence of 10mM GSH. The rapid and complete redox and pH stimuli release properties of the PU-SS-N nanocarrier will be a promising anticancer drug delivery system to ensure sufficient drug concentration to kill the cancer cells and to prevent the emergency of MDR. The in vitro cytotoxicity and cell uptake of the PTX-loaded micelles was also assessed in H460 and HepG2 cells.

X-ray visible and doxorubicin-loaded beads based on inherently radiopaque poly(lactic acid)-polyurethane for chemoembolization therapy.

The aim of current study was to develop drug-loaded polymeric beads with intrinsic X-ray visibility as embolic agents, targeting for noninvasive intraoperative location and postoperative examination during chemoembolization therapy. To endow polymer with inherent radiopacity, 4,4'-isopropylidinedi-(2,6-diiodophenol) (IBPA) was firstly synthesized and employed as a contrast agent, and then a set of radiopaque iodinated poly(lactic acid)-polyurethanes (I-PLAUs) via chain extender method were synthesized and characterized. These I-PLAU copolymers possessed sufficient radiopacity, in vitro non-cytotoxicity with human adipose-derived stem cells, and in vivo biocompatibility and degradability in rabbit model via intramuscular implantation. Doxorubicin (DOX), as a chemotherapeutic agent, was further incorporated into I-PLAU beads via a double emulsification (W/O/W) method. For drug release, two ratios of DOX-loaded I-PLAU beads exhibited calibrated size (200-550µm), porous internal structure, good X-ray visibility, evenly drug loading as well as tunable drug release. A preliminary test on in vitro tumor cell toxicity demonstrated that the DOX-loaded I-PLAU beads performed efficient anti-tumor effect. This study highlights novel X-ray visible drug-loaded I-PLAU beads used as promising embolic agents for non-invasive in situ X-ray tracking and efficient chemotherapy, which could bring opportunities to the next generation of multifunctional embolic agents.

Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling.

The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.

A comparative study between melt granulation/compression and hot melt extrusion/injection molding for the manufacturing of oral sustained release thermoplastic polyurethane matrices.

During this project 3 techniques (twin screw melt granulation/compression (TSMG), hot melt extrusion (HME) and injection molding (IM)) were evaluated for the manufacturing of thermoplastic polyurethane (TPU)-based oral sustained release matrices, containing a high dose of the highly soluble metformin hydrochloride. Whereas formulations with a drug load between 0 and 70% (w/w) could be processed via HME/(IM), the drug content of granules prepared via melt granulation could only be varied between 85 and 90% (w/w) as these formulations contained the proper concentration of binder (i.e. TPU) to obtain a good size distribution of the granules. While release from HME matrices and IM tablets could be sustained over 24h, release from the TPU-based TSMG tablets was too fast (complete release within about 6h) linked to their higher drug load and porosity. By mixing hydrophilic and hydrophobic TPUs the in vitro release kinetics of both formulations could be adjusted: a higher content of hydrophobic TPU was correlated with a slower release rate. Although mini-matrices showed faster release kinetics than IM tablets, this observation was successfully countered by changing the hydrophobic/hydrophilic TPU ratio. In vivo experiments via oral administration to dogs confirmed the versatile potential of the TPU platform as intermediate-strong and low-intermediate sustained characteristics were obtained for the IM tablets and HME mini-matrices, respectively.

Phospholipid End-Capped Acid-Degradable Polyurethane Micelles for Intracellular Delivery of Cancer Therapeutics.

Nanoscale drug carriers fabricated by phospholipid end-capped polyurethane bearing acetal backbones that degrade in acidic conditions are fabricated. These micelles effectively allow drugs to enter the blood circulation, and then disintegrate in acidic endosomes and lysosomes for intelligent delivery of payloads.

The value of polyurethane-cuffed endotracheal tubes to reduce microaspiration and intubation-related pneumonia: a systematic review of laboratory and clinical studies.

BACKGROUND: When conventional high-volume, low-pressure cuffs of endotracheal tubes (ETTs) are inflated, channel formation due to folds in the cuff wall can occur. These channels facilitate microaspiration of subglottic secretions, which is the main pathogenic mechanism leading to intubation-related pneumonia. Ultrathin polyurethane (PU)-cuffed ETTs are developed to minimize channel formation in the cuff wall and therefore the risk of microaspiration and respiratory infections. METHODS: We systematically reviewed the available literature for laboratory and clinical studies comparing fluid leakage or microaspiration and/or rates of respiratory infections between ETTs with polyvinyl chloride (PVC) cuffs and ETTs with PU cuffs. RESULTS: The literature search revealed nine in vitro experiments, one in vivo (animal) experiment, and five clinical studies. Among the 9 in vitro studies, 10 types of PU-cuffed ETTs were compared with 17 types of PVC-cuffed tubes, accounting for 67 vs. 108 experiments with 36 PU-cuffed tubes and 42 PVC-cuffed tubes, respectively. Among the clinical studies, three randomized controlled trials (RCTs) were identified that involved 708 patients. In this review, we provide evidence that PU cuffs protect more efficiently than PVC cuffs against fluid leakage or microaspiration. All studies with leakage and/or microaspiration as the primary outcome demonstrated significantly less leakage (eight in vitro and two clinical studies) or at least a tendency toward more efficient sealing (one in vivo animal experiment). In particular, high-risk patients intubated for shorter periods may benefit from the more effective sealing capacity afforded by PU cuffs. For example, cardiac surgery patients experienced a lower risk of early postoperative pneumonia in one RCT. The evidence that PU-cuffed tubes prevent ventilator-associated pneumonia (VAP) is less robust, probably because microaspiration is postponed rather than eliminated. One RCT demonstrated no difference in VAP risk between patients intubated with either PU-cuffed or PVC-cuffed tubes, and one before-after trial demonstrated a favorable reduction in VAP rates following the introduction of PU-cuffed tubes. CONCLUSIONS: Current evidence can support the use of PU-cuffed ETTs in high-risk surgical patients, while there is only very limited evidence that PU cuffs prevent pneumonia in patients ventilated for prolonged periods.

Preparation and characterization of naproxen-loaded electrospun thermoplastic polyurethane nanofibers as a drug delivery system.

The design and production of drug-loaded nanofiber based materials produced by electrospinning is of interest for use in innovative drug delivery systems. In the present study, ultra-fine fiber mats of thermoplastic polyurethane (TPU) containing naproxen (NAP) were successfully prepared by electrospinning from 8 and 10% (w/w) TPU solutions. The amount of NAP in the solutions was 10 and 20% based on the weight of TPU. The collection period of the drug-loaded electrospun TPU fibers was 5, 10 and 20h, and they were characterized by FTIR, DSC and TGA analysis. The morphology of the NAP-loaded electrospun TPU fiber mats was smooth, and the average diameters of these fibers varied between 523.66 and 723.50nm. The release characteristics of these fiber mats were determined by the total immersion method in the phosphate buffer solution at 37°C. It was observed that the collection period in terms of the mat thickness played a major role in the release rate of NAP from the electrospun TPU mats.

Inspired by nonenveloped viruses escaping from endo-lysosomes: a pH-sensitive polyurethane micelle for effective intracellular trafficking.

A multifunctional drug delivery system (DDS) for cancer therapy still faces great challenges due to multiple physiological barriers encountered in vivo. To increase the efficacy of current cancer treatment a new anticancer DDS mimicking the response of nonenveloped viruses, triggered by acidic pH to escape endo-lysosomes, is developed. Such a smart DDS is self-assembled from biodegradable pH-sensitive polyurethane containing hydrazone bonds in the backbone, named pHPM. The pHPM exhibits excellent micellization characteristics and high loading capacity for hydrophobic chemotherapeutic drugs. The responses of the pHPM in acidic media, undergoing charge conversion and hydrophobic core exposure, resulting from the detachment of the hydrophilic polyethylene glycol (PEG) shell, are similar to the behavior of a nonenveloped virus when trapped in acidic endo-lysosomes. Moreover, the degradation mechanism was verified by gel permeation chromatography (GPC). The endo-lysosomal membrane rupture induced by these transformed micelles is clearly observed by transmission electron microscopy. Consequently, excellent antitumor activity is confirmed both in vitro and in vivo. The results verify that the pHPM could be a promising new drug delivery tool for the treatment of cancer and other diseases.

Multifunctional cationic polyurethanes designed for non-viral cancer gene therapy.

Nano-polyplexes from bioreducible cationic polymers have a massive promise for cancer gene therapy. However, the feasibility of cationic polyurethanes for non-viral gene therapy is so far not well studied. In this work, a linear cationic polyurethane containing disulfide bonds, urethane linkages and protonable tertiary amino groups was successfully generated by stepwise polycondensation reaction between 2,2'-dithiodiethanol bis(p-nitrophenyl carbonate) and 1,4-bis(3-aminopropyl)piperazine (BAP). We confirmed that the cationic polyurethane (denoted as PUBAP) displayed superior gene delivery properties to its cationic polyamide analogue, thus causing higher in vitro transfection efficiency in MCF-7 and SKOV-3 cells. Besides, further folate-PEGylation and hydrophobic deoxycholic acid (DCA) conjugation to amino-containing PUBAP can be conducted to afford multifunctional polyurethane gene delivery system. After optimization, folate-decorated nano-polyplexes from the PUBAP conjugated with 8 folate-PEG chains and 12 DCA residues exhibited superb colloidal stability under physiological conditions, and performed rapid uptake via folate receptor-mediated endocytosis, efficient intracellular gene release and nucleus translocation into SKOV-3 cells in vitro and in vivo. Importantly, PUBAP based polyplexes possess low cytotoxicity as a result of PUBAP biodegradability. Therefore, marked growth inhibition of SKOV-3 tumor xenografted in Balb/c nude mice was achieved with negligible side effects on the mouse health after intravenous administration of PUBAP based polyplexes with a therapeutic plasmid encoding for TNF-related apoptosis-inducing ligand. This work provides a new insight into biomedical application of bio-responsive polyurethanes for cancer therapy. STATEMENT OF SIGNIFICANCE: In this study, we have confirmed that disulfide-based cationic polyurethane presents a new non-viral vector for gene transfer and cancer gene therapy. The significance of this work includes: (1) design and synthesis of a group of novel disulfide-based cationic polyurethane by non-isocyanate chemistry; (2) comparative study of transfection activity between cationic polyurethanes and cationic polyamides; (3) feasibility of bioreducible cationic polyurethanes for in vivo cancer gene therapy.

Fluoride Varnishes--Is There a Correlation Between Fluoride Release and Deposition on Enamel?

PURPOSE: Fluoride uptake of enamel after application of fluoride varnishes was compared with fluoride release into artificial saliva. The hypothesis was that fluoride uptake is higher for products exhibiting faster fluoride release. MATERIALS AND METHODS: Fluoride varnishes, i.e. Fluor Protector S, Duraphat, MI Varnish, Clinpro White Varnish, Profluorid Varnish and Enamel Pro Varnish were applied on bovine enamel specimens. Subsequently, specimens were incubated in artificial saliva. After removal of the varnishes, surface bound fluoride was extracted with potassium hydroxide and measured with an ion-selective electrode. Structurally bound fluoride was etched from the same specimens with perchloric acid. Fluoride release of varnish films into artificial saliva was measured for comparison. RESULTS: After 4 h in artificial saliva, the highest total enamel fluoride uptake of 47.9 µg F·cm-² was found with Fluor Protector S, followed by Enamel Pro Varnish with 22.1 µg F·cm-². The other products ranged between 12-16 µg F·cm-². This was several times higher than the negative control. Fluoride uptake did not correlate with release into artificial saliva. During the first 4 h, Duraphat released the lowest and MI Varnish the highest amount of fluoride with 7.7 and 249 µg F·cm-², respectively. The fluoride uptake of these two products was not statistically different. CONCLUSION: Enamel fluoride uptake cannot be predicted from the fluoride release rate of a product. Hence, based on the results of this study, fluoride release into artificial saliva is no measure for the efficacy of a fluoride varnish.