Ultrasound-Triggered Microbubbles: Novel Targeted Core-Shell for the Treatment of Myocardial Infarction Disease.

Myocardial infarction (MI) is known as a main cardiovascular disease that leads to extensive cell death by destroying vasculature in the affected cardiac muscle. The development of ultrasound-mediated microbubble destruction has inspired extensive interest in myocardial infarction therapeutics, targeted delivery of drugs, and biomedical imaging. In this work, we describe a novel therapeutic ultrasound system for the targeted delivery of biocompatible microstructures containing basic fibroblast growth factor (bFGF) to the MI region. The microspheres were fabricated using poly(lactic-co-glycolic acid)-heparin-polyethylene glycol- cyclic arginine-glycine-aspartate-platelet (PLGA-HP-PEG-cRGD-platelet). The micrometer-sized core-shell particles consisting of a perfluorohexane (PFH)-core and a PLGA-HP-PEG-cRGD-platelet-shell were prepared using microfluidics. These particles responded adequately to ultrasound irradiation by triggering the vaporization and phase transition of PFH from liquid to gas in order to achieve microbubbles. Ultrasound imaging, encapsulation efficiency cytotoxicity, and cellular uptake of bFGF-MSs were evaluated using human umbilical vein endothelial cells (HUVECs) in vitro. In vivo imaging demonstrated effective accumulation of platelet- microspheres injected into the ischemic myocardium region. The results revealed the potential use of bFGF-loaded microbubbles as a noninvasive and effective carrier for MI therapy.

Therapeutic contact lenses for the treatment of corneal and ocular surface diseases: Advances in extended and targeted drug delivery.

The eye is one of the most important organs in the human body providing critical information on the environment. Many corneal diseases can lead to vision loss affecting the lives of people around the world. Ophthalmic drug delivery has always been a major challenge in the medical sciences. Since traditional methods are less efficient (∼5%) at delivering drugs to ocular tissues, contact lenses have generated growing interest in ocular drug delivery due to their potential to enhance drug bioavailability in ocular tissues. The main techniques used to achieve sustained release are discussed in this review, including soaking in drug solutions, incorporating drug into multilayered contact lenses, use of vitamin E barriers, molecular imprinting, nanoparticles, micelles and liposomes. The most clinically relevant results on different eye pathologies are presented. In addition, this review summarizes the benefits of contact lenses over eye drops, strategies for incorporating drugs into lenses to achieve sustained release, results of in vitro and in vivo studies, and recent advances in the commercialization of therapeutic contact lenses for allergic conjunctivitis.

Electrospun POSS integrated poly(carbonate-urea)urethane provides appropriate surface and mechanical properties for the fabrication of small-diameter vascular grafts.

This study developed a platform for fabricating small-diameter vascular grafts using electrospun poly(carbonate-urea)urethane bonded with different concentrations of POSS nanocage. The characteristics of electrospun POSS-PCUUs were investigated by ATR-FTIR, 1HNMR, EDS, SEM, AFM, WCA, and DSC analyses. Besides, mechanical attributes such as tensile strength, modulus, elastic recovery, and inelastic behaviors were monitored. The survival rate and cellular attachment capacity were studied using human endothelial cells during a 7-day culture period. The results showed that electrospun nanofibers with 6 wt.% POSS-PCUU had better surface properties in terms of richness of POSS nanocage with notable improved mechanical strength and hysteresis loss properties (p < 0.05). The surface roughness of electrospun 6 wt.% POSS-PCUU reached 646 ± 10 nm with statistically significant differences compared to the control PCUU and groups containing 2, 4 wt.% POSS-PCUU (p < 0.05). The addition of 6 wt.% POSS increased the ultimate mechanical strength of nanofibers related to control PCUU and other groups (p < 0.05). The expansion of human endothelial cells on the 6 wt.% POSS-PCUU surface increased the viability reaching maximum levels on day 7 (p < 0.05). Immunofluorescence imaging using DAPI staining displayed the formation single-layer endothelial barrier at the luminal surface, indicating an appropriate cell-to-cell interaction.

Thermo/pH dual-responsive micelles based on the host-guest interaction between benzimidazole-terminated graft copolymer and ß-cyclodextrin-functionalized star block copolymer for smart drug delivery.

Novel temperature and pH dual-sensitive amphiphilic micelles were fabricated exploiting the host-guest interaction between benzimidazole-terminated PHEMA-g-(PCL-BM) and ß-CD-star-PMAA-b-PNIPAM. The fabricated graft copolymer had a brush-like structure with star side chains. The micelles were utilized as dual-responsive nanocarriers and showed the LCST between 40 and 41 °C. The acidic pH promoted the dissociation of the PHEMA-g-(PCL-BM: ß-CD-star-PMAA-b-PNIPAM) micelles. DOX.HCl was loaded into the core of the micelles during self-assembly in an aqueous solution with a high encapsulation efficacy (97.3%). The average size of the amphiphilic micelles was about 80 nm, suitable size for the enhanced permeability and retention effect in tumor vasculature. In an aqueous environment, these micelles exhibited very good self-assembly ability, low CMC value, rapid pH- and thermo-responsiveness, optimal drug loading capacity, and effective release of the drug. The biocompatibility was confirmed by the viability assessment of human breast cancer cell line (MCF-7) through methyl tetrazolium assay. DOX-loaded micelles displayed excellent anti-cancer activity performance in comparison with free DOX.

Drug delivery to the anterior segment of the eye: A review of current and future treatment strategies.

Research in the development of ophthalmic drug formulations and innovative technologies over the past few decades has been directed at improving the penetration of medications delivered to the eye. Currently, approximately 90% of all ophthalmic drug formulations (e.g. liposomes, micelles) are applied as eye drops. The major challenge of topical eye drops is low bioavailability, need for frequent instillation due to the short half-life, poor drug solubility, and potential side effects. Recent research has been focused on improving topical drug delivery devices by increasing ocular residence time, overcoming physiological and anatomical barriers, and developing medical devices and drug formulations to increase the duration of action of the active drugs. Researchers have developed innovative technologies and formulations ranging from sub-micron to macroscopic size such as prodrugs, enhancers, mucus-penetrating particles (MPPs), therapeutic contact lenses, and collagen corneal shields. Another approach towards the development of effective topical drug delivery is embedding therapeutic formulations in microdevices designed for sustained release of the active drugs. The goal is to optimize the delivery of ophthalmic medications by achieving high drug concentration with prolonged duration of action that is convenient for patients to administer.

Effect of poly(dimethylsiloxane)-block-poly(oligo (ethylene glycol) methacrylate) amphiphilic block copolymers on dermal fibroblast viability and proliferation.

In this work, well-defined poly(dimethylsiloxane)-b-poly(oligo (ethylene glycol) methacrylate) (PDMS-b-POEGMA) amphiphilic block copolymers were synthesized and their effect on human dermal fibroblast were investigated. Anionic ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP) were used to synthesis the block copolymers. The molecular weight of synthesized copolymers ranged from 1000 to 2300 Da by changing the number of both PDMS and POEGMA units. It was found that the copolymer having low molecular weight decreased the fibroblast viability and proliferation by inducing apoptosis. It was proved by flow cytometry and TUNEL assay that human dermal fibroblast experienced apoptosis after exposure to synthesized amphiphilic copolymers. The results of this work suggest the use of PDMS-b-POEGMA amphiphilic copolymers with low molecular weight for hypertrophic scars remediation.

Styrene monomer migration from polystyrene based food packaging nanocomposite: Effect of clay and ZnO nanoparticles.

Inhibition from migration of plastic ingredients such as styrene monomer (SM) is very important in food packaging industry. Styrene monomer is one of the substances which can potentially migrate from polystyrene based packaging. In the present study, organoclay and zinc oxide nanoparticles (ZnO-NPs) were used for decreasing of the SM migration into food simulants (10 and 50% ethanol (v/v)). A used GC-FID method for measuring of the migrated SM showed good precision and accuracy. Maximum reduction of SM migration into 10% and 50% ethanol (24 h storage at 40 °C) were observed in the polystyrene/nanoclay and polystyrene/ZnO samples, respectively. The SM migration data in 50% ethanol at 5 °C followed from Fickian diffusion law and the lowest diffusion coefficient (2.89 × 10-14 cm2/s) was observed in the polystyrene/ZnO/nanoclay samples.

Effects of different etching strategies on the microtensile repair bond strength of beautifil II giomer material.

BACKGROUND: Considering the differences in the filler particles between giomer and conventional composite resins and the importance of these fillers in the repair bond strength, the aim was to evaluate the effects of different etching strategies with phosphoric acid (PA) and hydrofluoric acid (HF) on the microtensile repair bond strength (µTRBS) of giomer. MATERIAL AND METHODS: Ten giomer blocks were randomly assigned into 10: 1) control; 2) 37%PA-20s; 3) 3%HF-20s; 4) 3%HF-120s; 5) 9.6%HF-20s; 6) 9.6%HF-120s; 7) 37%PA-20s + 3%HF-120s; 8) 37%PA-20s + 9.6%HF-120s; 9) 3%HF-120s + 37%PA-20s; 10) 9.6%HF-120s + 37%PA-20s. In all groups, the One-Step Plus bonding system was applied and the new giomer block was bonded to the existing giomer. After cross-sectional cutting, 18 samples were prepared from each block and the µTRBS of the samples was measured at a strain rate of 0.5 mm/min. Data were analyzed with one-way ANOVA and post hoc Tukey tests (P<0.05). RESULTS: The µTRBS in groups 4, 5, 6, 7, 8 and 10 were significantly higher than that in the control group (P<0.05). The µTRBS in group 2 was even less than that in the control group (P<0.001). The highest µTRBS was recorded in group 10, which was significantly different from those in groups 3, 4 and 9 (P<0.05). In addition, the differences between group 9 and groups 6, 7 and 8 were significantly different (P<0.05). CONCLUSIONS: Etching with PA resulted in a decrease in µTRBS. Etching with HF, except for 3%HF-20s and HF after etching with PA, resulted in a significant increase in giomer`s µTRBS. An increase in the application time of 3%HF resulted in a significant increase in the µTRBS. Key words:Dental restoration repair, Hydrofluoric acid, Phosphoric acid, etching.

Investigation of different core-shell toward Janus morphologies by variation of surfactant and feeding composition: A study on the kinetics of DOX release.

Composite particles with two individual hydrophilic parts were synthesized via seeded emulsion polymerization. As first part, nearly-monodisperse ethylene glycol dimethacrylate (EGDMA)-crosslinked poly(acrylic acid) (PAA) particles were synthesized by distillation precipitation polymerization (DPP). These particles were used as seeds in emulsion polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA). Effects of type of surfactant, monomers/seed weight ratio and amount of shell crosslinker on the synthesized composite particles' morphology were studied. Different morphologies consisting of core-shell, Janus type, raspberry-like and porous core-shell structures were investigated by variations of polymerization parameters. Different structures were chosen as drug carriers and subjected to DOX loading and release system. Results showed that amount of drug loading and extent of release were strongly dependent on the structure of carriers whereas for all carriers, DOX was released more rapid. Kinetics of release was evaluated by different mathematical models to investigate the release mechanism through composite particles. Results showed that only Korsmeyer-Peppas model fitted the drug release data and other ones were inappropriate in this field.

Using Chitosan/CHPATC as coagulant to remove color and turbidity of industrial wastewater: Optimization through RSM design.

One of the most important solid-liquid separation processes is coagulation and flocculation that is extensively used in the primary treatment of industrial wastewater. The biopolymers, because of biodegradable properties and low cost have been used as coagulants. In this study, chitosan as a natural coagulant of choice, was modified by (3-chloro 2-hydroxypropyl)trimethylammonium chloride and was used to remove the color and turbidity of industrial wastewater. To evaluate the effect of pH, settling time, the initial turbidity of wastewater, the amount of coagulant, and the concentration of dye (Melanoidin) were chosen to study their effects on removal of wastewater color and turbidity. The experiments were done in a batch system by using a jar test. To achieve the optimum conditions for the removal of color and turbidity, the response surface methodology (RSM) experimental design method was used. The results obtained from experiments showed that the optimum conditions for the removal of color were as: pH = 3, concentration of dye = 1000 mg/L, settling time = 78.93 min, and dose of coagulant = 3 g/L. The maximum color removal in these conditions was predicted 82.78% by the RSM model. The optimal conditions for the removal of turbidity of the waste water were as: pH = 5.66, initial turbidity = 60 NTU, settling time = 105 min, and amount of coagulant = 3 g/L. The maximum turbidity removal in these circumstances was predicted 94.19% by the model. The experimental results obtained in optimum conditions for removal of color and turbidity were 76.20% and 90.14%, respectively, indicating the high accuracy of the prediction model.

Bioinspired fully physically cross-linked double network hydrogels with a robust, tough and self-healing structure.

The conventional covalently cross-linked double network (DN) hydrogels with high stiffness often show low toughness and self-healing property due to the irreversible bond breakages in their networks. Therefore, scarcity of hydrogels that possess simultaneous features of stiffness, toughness, and autonomous self-healing properties at the same time remains a great challenge and seriously limits their biomedical applications. While, many natural materials acquire these features from their dynamic sacrificial bonds. Inspired by biomaterials, herein we propose a novel strategy to design stiff, tough and self-healing DN gels by substitution of both covalently cross-linked networks with strong, dynamic hydrogen bond cross-linked networks. The prepared fully physically cross-linked DN gels composed of strong agar biopolymer gel as the first network and tough polyvinyl alcohol (PVA) biopolymer gel as the second network. The DN gels demonstrated multiple-energy dissipating mechanisms with a high modulus up to 2200kPa, toughness up to 2111kJm-3, and ability to self-heal quickly and autonomously with regaining 67% of original strength only after 10min. The developed DN gels will open a new avenue to hydrogel research and holds high potential for diverse biomedical applications, such as scaffold, cartilage, tendon and muscle.

Mimicking the quasi-random assembly of protein fibers in the dermis by freeze-drying method.

Freeze-drying is extensively used for fabrication of porous materials in tissue engineering and biomedical applications, due to its versatility and use of no toxic solvent. However, it has some significant drawbacks. Conventional freeze-drying technique leads to the production of heterogeneous porous structures with side orientated columnar pores. As the top and bottom surfaces of the sample are not in contact with similar environments, different rates of heat transfer in the surfaces and the temperature gradient across the sample establish the preferential direction of heat transfer. To achieve a scaffold with a desirable microstructure for skin tissue engineering, freeze-drying method was modified by controlling the rate of cooling and regulation of heat transfer across the sample during the freezing step. It could create a homogeneous porous structure with more equiaxed non-oriented pores. Freezing the polymeric solution in the aluminum mold enhanced pore interconnectivity relative to the polystyrene mold. Recrystallization process was discussed how to influence the mean pore size of the scaffold when the final freezing temperature varied. Higher final freezing temperature can easily provide the energy required for the recrystallization process, which lead to enlarged ice crystals and resulting pores.