Novel polyurethane-based ionene nanoparticles electrostatically stabilized with hyaluronic acid for effective gene therapy.

Gene therapy is considered to be a valuable strategy for effective cancer treatment. However, the development of effective delivery systems that can specifically deliver gene materials, such as siRNA to tumor tissues plays a critical role in cancer therapy. In the present study, we have developed a novel complex that is based on an electrostatic interaction between cationic polyurethane ionene (CPUI) nanoparticles and an anti-signal transducer and activator of transcription 3 (STAT3) siRNA. For active targeting, hyaluronic acid (HA) was used to coat the complexes, which significantly reduced the cytotoxicity of the blank nanocarriers while demonstrating high transport efficiency of the siRNA via the CD44-mediated endocytosis pathway in MCF-7 breast cancer cells. The targeted nanocarriers (HA/CPUI/siRNA) showed significantly higher cellular internalization in flow cytometry and confocal microscopy compared with the non-targeted system (CPUI/siRNA). In addition, the incorporation of HA on the surface of the complexes resulted in significantly greater suppression of the STAT3 gene compared to the corresponding non-targeted formulation. Whole-body fluorescence images showed more significant tumor accumulation of the targeted nanocarriers in 4T1 breast tumor-bearing mice. Therefore, HA/CPUI/siRNA nanocarriers are an interesting option for the siRNA-targeted treatment of breast cancer cells.

Waterborne polyurethane magnetic nanomicelles with magnetically governed functions for breast cancer therapy.

Drug delivery strategies aim to maximize a drug's therapeutic efficiency by increasing the drug's concentration at the target site while minimizing delivery to off-target tissues. There is a great deal of interest in using magnetic nanoparticles in combination with applied magnetic fields to selectively control drug accumulation and release in target tissue while minimizing effects on other tissues. In this study, a magnetic targeted drug delivery system based on waterborne polyurethane nanomicelles was prepared by encapsulating hydrophobic doxorubicin (DOX, model drug) and hydrophobic oleic acid-superparamagnetic nanoparticles (SPION-OA) into the hydrophobic core of waterborne polyurethane micelles (CPUM) using the solvent evaporation method. The prepared drug-loaded magnetomicelles (CPUM-DOX-SPION) had a spherical shape with an average diameter of 158 nm. The magnetomicelles showed superparamagnetic properties with excellent magnetic resonance imaging (MRI) contrast effects and T2 relaxation in vitro. In the absence and presence of a magnetic field, the cytocompatibility and cellular uptake of the samples were assessed by MTT assay and flow cytometry, respectively, and the cells were imaged with a confocal microscope. Application of the magnetic field increased cellular cytotoxicity and cellular uptake in association with improved DOX delivery. In addition, the in vivo study of tumor volume showed that tumor growth of the mice group treated with CPUM-DOX-SPION in the presence of an external magnetic field was significantly retarded, with no apparent loss of body weight, compared with the same magnetomicelles in the absence of the magnetic field and with free DOX at the same dose. Moreover, the in vivo MRI experiment indicated the potential of these magnetomicelles as a probe in MRI diagnosis for tumor targeting, and the results showed that magnetically guided delivery of CPUM-SPION magnetomicelles into tumors could significantly improve the targeting efficacy. All the results suggest that the prepared novel magnetomicelles will be promising theranostic systems for effective magnetically guided delivery of chemotherapeutic agents and image-guided personalized medicine.

Poly(vinyl alcohol)-gelatin crosslinked by silane-functionalized guanidyl-hydroxyurethane oligomer as contact-killing non-leaching antibacterial wound dressings.

The present work aims to prepare efficient wound dressing with noncytotoxicity, proper mechanical strength, and the ability to preserve a hygienic environment over wounded skin tissue. To fulfill this goal, the synthesis of a novel silane crosslinking agent with antibacterial guanidinium chloride functional group is considered. The resulting reagent was applied to make a series of film-type stable crosslinked networks composed of poly(vinyl alcohol) and gelatin. The potential protection of wounds from external forces was confirmed, as these films had a very good tensile strength (16-31 MPa) and good elongation (54%-101%) under dry conditions. The good dimensional strength of dressings was preserved after hydration with simulated wound exudates. Based on the calculated fluid handling capacity of the prepared dressings (2.43-3.54 g 10-1cm-2d-1), they were suitable for treating wounds with 'light' to 'moderate' exudate volume. All the prepared dressings showed very good biocompatibility, as determined by the high viability of fibroblast cells directly contacted with dressing (over 80%) or leachates extracted from them (over 90%). In addition, dressings functionalized with guanidinium groups could effectively kill representative gram-positive and gram-negative bacterial strains.

Synthesis, characterization, photo-polymerization, hydrolytic stability, and etching behavior of new self-etch adhesive monomers.

Considering the poor hydrolytic stability of the most methacrylate-based functional monomers of self-etch dental adhesives in acidic and aqueous conditions, in this study allyl-based photo-polymerizable self-etch monomers was synthesized in order to improve the hydrolytic stability. The new self-etch monomers based on phosphonic acid functional groups were synthesized through a two-step procedure. First, phosphoric anhydride, poly-phosphoric acid, and polyethylene glycol were reacted to produce phosphate ester precursor (P-PEG-P). Next, allyl 2, 3-epoxypropyl ether was reacted with P-PEG-P to synthesize allyl self-etch monomer. Glycidyl methacrylate was also reacted with P-PEG-P to synthesize a methacrylate self-etch analogue monomer. The monomers were characterized using FTIR and 1H-NMR spectroscopy. The viscosities of monomers were measured using a rheometer. The degree photopolymerization conversion of monomers was measured using FTIR spectroscopy. The pH assay was performed by a digital pH-meter. The etching behavior of the monomers on human teeth was studied using scanning electron microscopy (SEM). Thermo-gravimetric analysis (TGA) was performed to evaluate the possible interaction of the monomers with tricalcium phosphate (TCP). The solubility of synthesized monomers was examined in ethanol, acetone, and water. The hydrolytic stability of cured resins in artificial saliva during 4 months was also surveyed. The synthesis of new self-etching monomers was successfully confirmed by spectroscopy analyses. The results represented appropriate viscosity of self-etching monomers around 1 (Pa s). The resin containing methacrylate monomer exhibited its degree of conversion is more than that of allyl monomer (p < 0.05). The allyl and methacrylate self-etch monomers exhibited pH values of 1.2 and 1.3, respectively. SEM micrograph verified that the synthesized monomers were able to suitable etching of the enamel human premolar teeth. The data obtained from TGA tests revealed that thermal stability of (TCP) containing monomers is enhanced. Also, the monomers exhibited an excellent solubility in polar solvents, but when they are mixed with TCP, they are not, anymore, dissolved in these solvents. Furthermore, the allyl monomer showed higher hydrolytic stability than the methacrylate monomer. The new photo-polymerizable acidic monomer based on allyl functionality showed enhanced hydrolytic stability compared to methacrylate-based monomer. It may be considered as a promising monomer for self-etch dental adhesives.

Design of novel polyurethane-based ionene nanocarriers for cancer therapy: Synthesis, in-vitro, and in-vivo studies.

New strategies for constructing versatile nanocarriers are needed for cancer therapy to overcome the multiple challenges of targeted delivery. This work explores the advantages of polyurethane with main-chain quaternary ammonium salt moieties (ionene) as a novel carrier for targeted drug delivery. We have developed a novel cationic soybean oil-based polyurethane ionene nanocarrier (CPUI) that can act as an effective anticancer agent and efficiently deliver the anticancer drug 5-fluorouracil (5FU). We also report a potential anticancer drug delivery system targeting the folate receptor. In vitro experiments with blank CPUI carriers on the 4T1 (mouse breast cancer cell line) and the NIH-3T3 (mouse fibroblast cell line) revealed high cytotoxicity for the cancer cells but only low cytotoxicity for the normal fibroblast cells. The CPUI nanoparticles were readily loaded with 5FU (5FU-CPUI) in water using electrostatic interactions between the cationic quaternary ammonium groups of ionene and the anionic 5FU. The in vivo study in mice with tumors showed that the blank CPUI carriers significantly inhibited tumor growth, even more than the free drug (5FU). The inhibitory effect on tumor growth was slightly enhanced when the carriers were loaded with 5FU. The prepared nanoparticles had a high loading capacity of 41.8 %. Further enhancement of the inhibitory effect was observed when folic acid (FA) was added as a targeting moiety to the system via ion exchange with the bromine counterion of the quaternary ammonium moieties. The results suggest that the efficacy of FA-CPUI-5FU nanoparticles as vehicles for drug delivery can be enhanced via folate receptor (FR) mediated endocytosis in 4T1 cells and these novel nanocarriers may provide a potential platform for effective targeted drug delivery to tumor tissue and breast cancer therapy in the clinic.

Redox-responsive waterborne polyurethane nanocarriers for targeted doxorubicin delivery.

Nanocarriers of different origins that respond to stimuli have been synthesized and used in various biomedical applications, such as intracellular drug delivery. To develop highly efficient nanocarriers, novel clickable and cleavable soybean oil-based polyurethane nanomicelles (CPUM), and polyurethane-hyaluronic acid nanomicelles (CPUM-HA) were prepared. The prepared nanocarriers exhibited controlling self-assembly properties, stimuli-responsiveness, good cytocompatibility, and high loading capacity for doxorubicin (DOX). The addition of the reducing agent glutathione (GSH) to the drug release medium resulted in GSH-triggered species size change (aggregation of nanomicelles) and enhanced release of DOX, leading to higher cytotoxicity in tumors. MTT, confocal laser scanning microscopy (CLSM), and flow cytometry results showed that the CPUM-HA-DOX nanocarriers exhibited increased cytotoxicity and cellular uptake compared to the CPUM-DOX nanocarriers. The in vivo and ex vivo results suggested that the CPUM-HA nanomicelles could provide a potential platform for effective targeted delivery of cytotoxic drug molecules to the tumor tissue and breast cancer therapy in the clinic.

A New Combination: Anti Glypican-3 scFv and Diphtheria Toxin with the Best Flexible Linker.

Along with all cancer treatments, including chemotherapy, radiotherapy, and surgery, targeting therapy is a new treatment manner. Immunotoxins are new recombinant structures that kill cancer cells by targeting specific antigens. Immunotoxins are composed of two parts: toxin moiety, which disrupts protein synthesis process, and antigen binding moiety that bind to antigens on the surface of cancer cells. Glypican 3 (GPC3) is an oncofetal antigen on the surface of Hepatocellular carcinoma (HCC) cells. In this study, truncated Diphtheria toxin (DT389) was fused to humanized scFv YP7 by one, two and three repeats of GGGGS linkers (DT389-(GGGGS)1-3YP7). In-silico and experimental investigation were performed to find out how many repeats of linker between toxin and scFv moieties are sufficient. Results of in-silico investigations revealed that the difference in the number of linkers does not have a significant effect on the main structures of the immunotoxin; however, the three-dimensional structure of two repeats of linker had a more appropriate structure compared to others with one and three linker replications. In addition, with enhancing the number of linkers, the probability of protein solubility has increased. Generally, the bioinformatics results of DT389-(GGGGS)2-YP7 structure showed that expression and folding is suitable; and YP7 scFv has appropriate orientation to bind GPC3. The experimental investigations indicated that the fusion protein was expressed as near to 50% soluble. Due to the high binding affinity of YP7 scFv and the proven potency of diphtheria in inhibiting protein synthesis, the proposed DT389-(GGGGS)2-YP7 immunotoxin is expected to function well in inhibiting HCC.

DT389-YP7, a Recombinant Immunotoxin against Glypican-3 That Inhibits Hepatocellular Cancer Cells: An In Vitro Study.

Hepatocellular carcinoma (HCC) is one of the high-metastatic types of cancer, and metastasis occurs in one-third of patients with HCC. To maintain the effectiveness of drug compounds on cancer cells and minimize their side effects on normal cells, it is important to use new approaches for overcoming malignancies. Immunotoxins (ITs), an example of such a new approach, are protein-structured compounds consisting of toxic and binding moieties which can specifically bind to cancer cells and efficiently induce cell death. Here, we design and scrutinize a novel immunotoxin against an oncofetal marker on HCC cells. We applied a truncated diphtheria toxin (DT389) without binding domain as a toxin moiety to be fused with a humanized YP7 scFv against a high-expressed Glypican-3 (GPC3) antigen on the surface of HCC cells. Cytotoxic effects of this IT were investigated on HepG2 (GPC3+) and SkBr3 (GPC3-) cell lines as positive- and negative-expressed GPC3 antigens. The dissociation constant (Kd) was calculated 11.39 nM and 18.02 nM for IT and YP7 scfv, respectively, whereas only IT showed toxic effects on the HepG2 cell line, and decreased cell viability (IC50 = 848.2 ng/mL). Changing morphology (up to 85%), cell cycle arrest at G2 phase (up to 13%), increasing intracellular reactive oxygen species (ROSs) (up to 50%), inducing apoptosis (up to 38% for apoptosis and 23% for necrosis), and an almost complete inhibition of cell movement were other effects of immunotoxin treatment on HepG2 cells, not on SkBr3 cell line. These promising results reveal that this new recombinant immunotoxin can be considered as an option as an HCC inhibitor. However, more extensive studies are needed to accomplish this concept.

Immunotoxins Immunotherapy against Hepatocellular Carcinoma: A Promising Prospect.

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Therefore, fighting against such cancer is reasonable. Chemotherapy drugs are sometimes inefficient and often accompanied by undesirable side effects for patients. On the other hand, the emergence of chemoresistant HCC emphasizes the need for a new high-efficiency treatment strategy. Immunotoxins are armed and rigorous targeting agents that can purposefully kill cancer cells. Unlike traditional chemotherapeutics, immunotoxins because of targeted toxicity, insignificant cross-resistance, easy production, and other favorable properties can be ideal candidates against HCC. In this review, the characteristics of proper HCC-specific biomarkers for immunotoxin targeting were dissected. After that, the first to last immunotoxins developed for the treatment of liver cancer were discussed. So, by reviewing the strengths and weaknesses of these immunotoxins, we attempted to provide keynotes for designing an optimal immunotoxin against HCC.

Enhanced healing of a full-thickness wound by a thermoresponsive dressing utilized for simultaneous transfer and protection of adipose-derived mesenchymal stem cells sheet.

To boost the healing process in a full-thickness wound, a simple and efficient strategy based on adipose-derived mesenchymal stem cells (ADSCs) transplantation is described in this work. To increase the chance of ADSCs immobilization in the wound bed and prevent its migration, these cells are fully grown on the surface of a thermoresponsive dressing membrane under in vitro condition. Then, the cells sheet with their secreted extracellular matrix (ECM) is transferred to the damaged skin with the help of this dressing membrane. This membrane remains on wound bed and acts both as a cell sheet transfer vehicle, after external reduction of temperature, and protect wound during the healing process like a common wound dressing. The visual inspection of wounded skin (rat animal model) at selected time intervals shows a higher wound closure rate for ADSCs treated group. For this group of rats, the better quality of reconstructed tissue is approved by results of histological and immunohistochemical analysis since the higher length of the new epidermis, the higher thickness of re-epithelialization layer, a higher level of neovascularization and capillary density, and the least collagen deposition are detected in the healed tissue.

Vegetable oil-based polyurethanes as antimicrobial wound dressings: in vitro and in vivo evaluation.

Preparation of efficient polyurethane-type wound dressings with tunable physicomechanical properties and widespread antimicrobial activity is considered in this work. A new type of soybean oil-based polyol with built-in urethane and quaternary ammonium groups is synthesized through a nonisocyanate route using carbonated soybean oil as an environmentally friendly, renewable resource-based raw material. Different formulations from this polyol and castor oil are prepared and converted to the polyurethane wound dressings via a reaction with isophorone diisocyanate. The dressing sample, with good cytocompatibility and efficient antimicrobial activity against various microbial strains, having tensile strength of 5 and 17 MPa at hydrated and dry state, elongation at the break of up to 400%, equilibrium water absorption and a water vapor transmission rate of 50% and 390 g m-2 day-1, is used for in vivo assay on a rat. Evaluation of the optimized dressing for a full-thickness non-sterilized wound has shown excellent progress of wound healing, since the tensile strength of regenerated skin reaches about 80% of normal healthy skin on day 21 after wounding. This has been significantly superior to the tensile strength of the regenerated skin of rats covered with non-antibacterial (∼50%) and cotton gauze (∼40%) dressings as blank and control groups.

Resveratrol-loaded polyurethane nanofibrous scaffold: viability of endothelial and smooth muscle cells.

Acellular small-caliber tissue-engineered vascular grafts (SCTEVGs) have low patency rate due to complications including thrombosis and intimal hyperplasia. Rapid endothelialization, antithrombosis and antiproliferation approaches are suitable for dispelling these complications. Nevertheless, common antithrombosis and antiproliferation techniques are usually incompatible with rapid endothelialization on vascular grafts. To overcome these obstacles, we developed nanofibrous polyurethane scaffolds loaded with resveratrol drug, which is a natural compound extracted from plants and shows multifaceted effects in cardiovascular protection. It was found that the tensile strength and Young's modulus in modified scaffolds were significantly increased by resveratrol loading into membranes. The tensile strengths and breaking strains of resveratrol-loaded scaffolds were close to that of native vessels. The resveratrol release profile from the nanofibrous scaffolds occurred in a sustained manner. The anti-thrombogenicity of resveratrol-loaded nanofibers increased compared to polyurethane alone, with the result that prolonged human blood clotting time and lower hemolysis were detected on these scaffolds. The viability of human umbilical vein endothelial cells and smooth muscle cells on resveratrol-loaded scaffolds was evaluated. Our findings demonstrated that resveratrol-loaded nanofibers resulted in not only appropriate antithrombotic properties, but the formation of a monolayer of endothelial cells on the scaffold surface and lower smooth muscle cell growth. These resveratrol-loaded nanofibers are suggested as potential scaffolds for SCTEVGs.

Ionic liquid tethered PEG-based polyurethane-siloxane membranes for efficient CO2/CH4 separation.

This study introduces a new polyethylene glycol (PEG) based polyurethane-siloxane membrane containing a quaternary ammonium ionic liquid for CO2/CH4 separation. The designed ionic liquid was prepared in two steps: (i) (3-chloropropyl)triethoxysilane (CPS) and N,N-dimethylpropyl amine (NDPA) were reacted with each other to form the methoxysilane-functionalized quaternary ammonium component, then (ii) chloride ion (Cl-) of the product was exchanged with tetrafluoroborate ion (BF4-). The resulting compound, a reactive methoxysilane-functionalized ionic liquid (Si-IL) was chemically anchored to the polymer backbone through the sol-gel hydrolysis and condensation reaction. Based on the permeation tests, the IL containing PEG-based polyurethane-siloxane membranes at different concentration of Si-IL (XSi-PPUIL) were found to be potential candidates for CO2 removal from CH4. For instance, the CO2/CH4 selectivity of XSi-PPUIL membranes with the Si-IL content of 10 wt% was 3.3-fold greater than the Si-IL free membranes; while, the CO2 permeability for IL tethered membranes was 9.7% higher than the corresponding IL-free membrane.

Antimicrobial wound dressings with high mechanical conformability prepared through thiol-yne click photopolymerization reaction.

Radical mediated photochemical thiol-yne click polymerization of thiol-terminated polyurethane prepolymers, with poly(ethylene glycol) soft segment at two different molecular weights, a propargyl terminated urethane crosslinker and silver salt was utilized to prepare versatile wound dressings containing well-dispersed Ag° nanoparticles produced via in situ reduction of Ag+ ions. The dressings with optimized chemical structure showed desirable fluid handling capacity (up to 4.84 g/10 cm2 d-1) to provide moist environment over damaged tissue. They were permeable to oxygen and carbon dioxide, therefore, the processes related to tissue regeneration of wound bed could be continued without problem. Their appropriate tensile strength (up to 3.87 MPa) and suitable conformability (less than 0.1% permanent set) enabled protection of damaged skin tissue from external physical forces during the healing process, even for wounds present at organs with a high degree of freedom. The proper cytocompatibility of the prepared dressings and their ability to support growth and proliferation of fibroblast cells as determined by wound scratch healing assay showed the potential utility of the dressings to motivate wound healing progression by migration of cells to the damaged area. In addition, these dressings with in situ formed silver nanoparticles exhibited promising antimicrobial activity against different bacterial and fungal strains, and consequently could encourage wound healing process by prevention from infection in the wound site.

Utilizing dextran to improve hemocompatibility of antimicrobial wound dressings with embedded quaternary ammonium salts.

Dextran, a polysaccharide with interfering effects on coagulation hemeostasis was utilized to compensate the hostile effects of quaternary ammonium salts (QAS) embed in the backbone of a wound dressing membrane as an antimicrobial agent. Despite the high antimicrobial efficiency of QAS, their adverse hemolytic effect on red blood cells is a challenging problem for using them as an active antiseptic agent in wound dressings. To this end, wound dressings made through the sol-gel hydrolysis and polycondensation reaction of a methoxysilane-functionalized quaternary ammonium compound (Si-RQ) and a methoxysilane terminated polyurethane prepolymer (Si-PPU), at different compositions, were surface modified with dextran. The final dressings were then subjected to various biological and physico-mechanical assays. The low hemolysis rate and prolonged clot formation on dextran-modified dressings confirmed their excellent hemocompatibility. Meanwhile, the optimized dressings preserved their excellent antimicrobial activity against both Gram-positive and Gram-negative bacteria and a fungal strain up to 100% killing efficiency. In addition, they exhibited very good cytocompatibility since the fibroblast cells could grow and proliferate efficiently on their surface. The recorded results confirmed the effectiveness of surface anchored dextran for regulation of hemocompatibility of QAS containing wound dressings without deterioration of their basic physical and biological properties.

Green and non-leaching anti-bacterial and cytocompatible coating with build-in quaternary ammonium salt derived from methoxysilane functionalized soybean oil.

Preparation and evaluation of non-leaching antimicrobial polymeric coatings, derived from soybean oil, against bacterial contamination of some metallic biomedical devices are described in this work. Cyclic carbonate derivative of soybean oil (CSBO) was subjected to the reaction with 3-aminopropyl trimethoxysilane to produce a methoxysilane functional soybean oil (Si-SBU) with urethane linkage. A quaternary ammonium salt containing fatty amide molecule with reactive siloxane moiety (Si-SBQ) was also synthesized from soybean oil. The antimicrobial coatings were prepared through sol-gel hydrolysis/condensation reactions of Si-SBU mixed with different concentrations of Si-SBQ under atmospheric moisture condition. The coatings demonstrated very good hardness (202-263 s-1) and superior adhesion strength (2.25-2.95 MPa) to aluminum plate as a model metallic substrate. The biological activities of these coatings were investigated against both fibroblast cells and microorganism strains of Meticillin-resistant S. aureus, P. aeruginosa, and C. albicans. The coatings showed excellent cytocompatibility as they could support growth and proliferation of fibroblast cells (95-98% viability) on their surface. Meanwhile, they showed a high bactericidal activity against all the selected microorganisms.

Polyurethane-Polycaprolactone Blend Patches: Scaffold Characterization and Cardiomyoblast Adhesion, Proliferation, and Function.

A remarkable challenge in myocardial tissue engineering is the development of biomimetic constructs that can potentially improve myocardial repair and regeneration. Polyurethane (PU) scaffolds are extensively utilized in the cardiovascular system. We have synthesized a new biodegradable poly(ester-ether urethane urea) (PEEUU) using a new and simple method. To enhance mechanical and physicochemical properties, the PEEUU was blended with polycaprolactone (PCL). We then fabricated a series of new PU-PCL scaffolds. The scaffolds were then characterized using SEM, porosity measurement, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), DSC, water contact angle measurement, swelling measurement, in vitro degradation rate, and mechanical tests. Expression of the cardiac-specific proteins on the scaffolds was investigated using immunofluorescence staining and quantitative real-time PCR. The elasticity of blends increased with an increase of PEEUU. In the blend scaffolds, the size and interconnectivity of pores were in an appropriate range (142-170 µm) as reported in the literature. These blend scaffolds revealed high cell metabolic activity for cardiomyoblasts and also enabled cells to proliferate and express cardiac marker proteins at higher rates. Histological examination of subcutaneously transplanted scaffolds after two months revealed degradation in the blend scaffolds. It is demonstrated that functionality of cells is sensitive to the composition of biomaterials used, and the effective cell-biomaterial interactions are critical in order to create a functional tissue engineered product that allows seeded cells to develop their normal activity. The PEEUU-PCL blends could potentially provide a versatile platform to fabricate functional scaffolds with an effective cell-biomaterial interaction for cardiac tissue regeneration.

Polyurethane/siloxane membranes containing graphene oxide nanoplatelets as antimicrobial wound dressings: in vitro and in vivo evaluations.

Preserving wounds from bacterial and fungal infections and retaining optimum moist environment over damaged tissue are major challenges in wound care management. Application of wound dressings with antimicrobial activity and appropriate wound exudates handling ability is of particular significance for promoting wound healing. To this end, preparation and evaluation of novel wound dres1sings made from polyurethane/siloxane network containing graphene oxide (GO) nanoplatelets are described. The particular sol-gel hydrolysis/condensation procedure applied for the preparation of dressings leads to an appropriate distribution of GO nanoplatelets in the dressing membranes. The crosslinked siloxane domains and the presence of GO nanoplatelets within polymeric chains offered necessary mechanical strength for dressings. Meanwhile, a combination of hydrophilic and hydrophobic moieties in dressing backbone enabled suitable wound exudate management. Therefore, both of physical protection from external forces and preservation of moist environment over wound were attained by using the designed dressings. Widespread antimicrobial activity against gram-positive, gram-negative and fungal strains was recorded for the dressing with the optimum amount of GO, meanwhile, very good cytocompatibility against fibroblast cells was noted for these dressings. In vivo assay of the GO containing dressing on rat animal model reveals that the dressing can promote wound healing by complete re-epithelization, enhanced vascularization and collagen deposition on healed tissue.

Application of arteether-loaded polyurethane nanomicelles to induce immune response in breast cancer model.

To concentrate a potent anticancer drug (Arteether) in tumor microenvironment, we encapsulated it in biodegradable and pH sensitive polyurethane (PU) nanomicelles (NMs). The nanocomplex was characterized by Fourier transform infrared (FTIR), dynamic light scattering (DLS). The loading capacity and release profile in pH of 5.4 and 7.4 were considered. The cytotoxicity effect was evaluated in vitro and in vivo settings. The level of IFN-γ and IL-4 cytokines of mice splenocytes were assessed by enzyme-linked immunosorbent assay (ELISA). The nanocomplex showed negative zeta charge of -26.2 mV, size of 42.30 nm and high loading capacity (92%). Release profile showed a faster rate of drug liberation at pH 5.4 as compared to that of pH 7.4. It indicated significant inhibitory effect on the growth of 4T1 cell line and increased IFN-γ level.

Bactericidal dental nanocomposites containing 1,2,3-triazolium-functionalized POSS additive prepared through thiol-ene click polymerization.

OBJECTIVE: Deterioration of mechanical strength for the dental composite containing ionic bactericidal compounds restricts the widespread utilization of this class of useful materials. This problem is originated from the reduction of the intermolecular interaction of polymeric network due to plasticization effect of absorbed water molecules penetrated between the chain segments. The main goal of this study is the synthesis of the highly efficient bactericidal additive with low hydrophilicity and consequently the least adverse effect on the final mechanical strength of the dental composite. METHODS: The bactericidal 1, 2, 3-triazolium functional groups were chemically anchored on the surface of hydrophobic POSS nanoparticles (Triazolium-POSS) and incorporated into a dental restorative system composed of a ternary thiol-allyl ether-methacrylate resin and glass fillers. A similar system was also prepared, in which the POSS additive was replaced with quaternized dimethyl aminoethyl methacrylate monomer (DMAEMA-BC). The chemical structure of POSS derivatives was evaluated by 1HNMR and FTIR spectra. The water uptake of dental composites was evaluated at days 1 and 14 after immersion into water. The bactericidal activity of composite specimens against Streptococcus mutans (ATCC 35668) was determined based on ASTM E 2180 - 07. The flexural properties of samples were investigated through three-point bending assay and the shrinkage-strain of photo-cured resins was measured using the bonded-disk technique. The degree of conversion (DC %) of methacrylate functions was followed by FTIR spectroscopy. MTT assay was performed to investigate the cytocompatibility of samples. RESULTS: Regardless of the partial increase in water uptake for Triazolium-POSS-containing sample, this parameter was much favor than the composite made from DMAEMA-BC. Therefore, the lower decline in flexural properties was recorded under the wet condition for the former system. Incorporation of Triazolium-POSS had no significant effect on shrinkage strain and cytocompatibility of composite specimen, meanwhile, a higher degree of conversion of methacrylate functional groups was recorded. The Triazolium-POSS-containing nano composite showed significantly higher bactericidal activity against Streptococcus mutans than another studied model system. SIGNIFICANCE: The new derivative of bactericidal POSS nanoparticles decorated with 1, 2, 3-Triazolium moieties is a highly efficient bactericidal compound. If Triazolium-POSS is incorporated into a proper dental resin formulation, it can provide a strong bactericidal activity for dental materials; in the meantime, it leads to minimum deterioration of their mechanical strength due to its low water uptake.