Comparative Investigation of Phenomenological Modeling for Hysteresis Responses of Magnetorheological Elastomer Devices.

Magnetorheological elastomer (MRE) is a type of magnetic soft material consisting of ferromagnetic particles embedded in a polymeric matrix. MRE-based devices have characteristics of adjustable stiffness and damping properties, and highly nonlinear and hysteretic force-displacement responses that are dependent on external excitations and applied magnetic fields. To effectively implement the devices in mitigating the hazard vibrations of structures, numerically traceable and computationally efficient models should be firstly developed to accurately present the unique behaviors of MREs, including the typical Payne effect and strain stiffening of rubbers etc. In this study, the up-to-date phenomenological models for describing hysteresis response of MRE devices are experimentally investigated. A prototype of MRE isolator is dynamically tested using a shaking table in the laboratory, and the tests are conducted based on displacement control using harmonic inputs with various loading frequencies, amplitudes and applied current levels. Then, the test results are used to identify the parameters of different phenomenological models for model performance evaluation. The procedure of model identification can be considered as solving a global minimization optimization problem, in which the fitness function is the root mean square error between the experimental data and the model prediction. The genetic algorithm (GA) is employed to solve the optimization problem for optimal model parameters due to its advantages of easy coding and fast convergence. Finally, several evaluation indices are adopted to compare the performances of different models, and the result shows that the improved LuGre friction model outperforms other models and has optimal accuracy in predicting the hysteresis response of the MRE device.

Self-Assembled Cubic Liquid Crystalline Nanoparticles for Transdermal Delivery of Paeonol.

BACKGROUND: The aim of this study was to optimize the preparation method for self-assembled glyceryl monoolein-based cubosomes containing paeonol and to characterize the properties of this transdermal delivery system to improve the drug penetration ability in the skin. MATERIAL AND METHODS: In this study, the cubic liquid crystalline nanoparticles loaded with paeonol were prepared by fragmentation of glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel by high-pressure homogenization. We evaluated the Zeta potential of these promising skin-targeting drug-delivery systems using the Malvern Zeta sizer examination, and various microscopies and differential scanning calorimetry were also used for property investigation. Stimulating studies were evaluated based on the skin irritation reaction score standard and the skin stimulus intensity evaluation standard for paeonol cubosomes when compared with commercial paeonol ointment. In vitro tests were performed on excised rat skins in an improved Franz diffusion apparatus. The amount of paeonol over time in the in vitro penetration and retention experiments both was determined quantitatively by HPLC. RESULTS: Stimulating studies were compared with the commercial ointment which indicated that the paeonol cubic liquid crystalline nanoparticles could reduce the irritation in the skin stimulating test. Thus, based on the attractive characteristics of the cubic crystal system of paeonol, we will further exploit the cosmetic features in the future studies. CONCLUSIONS: The transdermal delivery system of paeonol with low-irritation based on the self-assembled cubic liquid crystalline nanoparticles prepared in this study might be a promising system of good tropical preparation for skin application.

Imaging gastrointestinal damage due to acute mercury poisoning using a mitochondria-targeted dual near-infrared fluorescent probe.

Mercury (Hg) is one of the most widespread pollutants that pose serious threats to public health and the environment. People are inevitably exposed to Hg via different routes, such as respiration, dermal contact, drinking or diet. Hg poisoning could cause gingivitis, inflammation, vomiting and diarrhea, respiratory distress or even death. Especially during the developmental stage, there is considerable harm to the brain development of young children, causing serious symptoms such as intellectual disability and motor impairments, and delayed neural development. Therefore, it's of great significance to develop a specific, quick, practical and labor-saving assay for monitoring Hg2+. Herein, a mitochondria-targeted dual (excitation 700 nm and emission 728 nm) near-infrared (NIR) fluorescent probe JZ-1 was synthesized to detect Hg2+, which is a turn-on fluorescent probe designed based on the rhodamine fluorophore thiolactone, with advantages of swift response, great selectivity, and robust anti-interference capability. Cell fluorescence imaging results showed that JZ-1 could selectively target mitochondria in HeLa cells and monitor exogenous Hg2+. More importantly, JZ-1 has been successfully used to monitor gastrointestinal damage of acute mercury poisoning in a drug-induced mouse model, which provided a great method for sensing Hg species in living subjects, as well as for prenatal diagnosis.

Paclitaxel-nanocrystals-loaded network thermosensitive hydrogel for localised postsurgical recurrent of breast cancer after surgical resection.

The recurrence of cancer after local surgery has been a difficult problem in the clinic for a long time. In recent years, local treatment via drug-loaded thermosensitive hydrogels have become a promising strategy to prevent cancer recurrence. Thus, a thermosensitive hydrogel based on poloxamer 407, poloxamer 188 and the bioadhesive excipient carbomer 974P was designed to locally release paclitaxel and prevent local tumour recurrence after direct smearing of the hydrogel at the site of injury in the surgical cavity. To improve the local drug concentration, paclitaxel was prepared into nanocrystals via a wet mill process. A series of studies were performed on this paclitaxel nanocrystal thermosensitive hydrogel (PTX-NCS-gel), including examination of its rheological properties and in vitro release and dissolution studies. Moreover, a postoperative tumour recurrence mouse model was established to evaluate the antitumour effects of this thermosensitive hydrogel. The results showed that PTX-NCS-gel had a clear, regular network structure with excellent temperature sensitivity and could be gelated within minutes at 33.1 °C. Additionally, the rheological property investigation indicated that the hydrogel has proper viscoelasticity and self-recovery ability. In vivo imaging showed that PTX-NCS-gel inhibited both local tumour recurrence and distant metastasis. Moreover, PTX-NCS-gel has the following advantages: it is more convenient to administer, avoids strong allergic responses, and has fewer side effects on the liver and spleen. This hydrogel has the potential to serve as a powerful auxiliary medication to prevent postoperative local tumour recurrence.

Dasatinib self-assembled nanoparticles decorated with hyaluronic acid for targeted treatment of tumors to overcome multidrug resistance.

Multidrug resistance (MDR) and lack of targeting specificity are the main reasons why traditional drug therapies fail and produce toxic side effects in cancer chemotherapy. In order to increase targeting specificity and maximize therapeutic efficacy, new intelligent drug delivery systems are needed. In this study, we prepared the hyaluronic acid (HA) conjugated dasatinib (DAS) and D-α-tocopherol acid polyethylene glycolsuccinate (TPGS) copolymer nanoparticles (THD-NPs). The water solubility of the hydrophobic drug DAS was improved by chemically linking with HA. HA can bind to the over-expressed CD44 protein of tumor cells to increase targeting specificity, TPGS can inhibit the activity of P-glycoprotein (P-gp), and increase the intracellular accumulation of drugs. The prepared drug-loaded nanoparticle has a particle size of 82.23 ± 1.07 nm with good in vitro stability. Our in vitro studies showed that THD-NPs can be released more rapidly in a weakly acidic environment (pH = 5.5) than in a normal physiological environment (pH = 7.4), which can realize the selective release of nanoparticles in tumor cells. Compared to free drugs, THD-NPs showed more efficient cellular uptake, effectively increased the cytotoxic effect of DAS on nasopharyngeal carcinoma HNE1 cells drug resistance HNE1/DDP cells and increased the accumulation of drugs in HNE1/DDP cells, which may be due to the inhibitory effect of TPGS on the efflux function of P-gp. In vivo experiments showed that THD-NPs can effectively inhibit tumor growth without obvious side effects. In conclusion, the targeted and pH-sensitive nanosystem, we designed has great potential to overcome drug resistance and increase therapeutic effects in cancer treatment.

A multi-functional polymeric carrier for simultaneous positron emission tomography imaging and combination therapy.

Multifunctional nanoplatforms offering simultaneous imaging and therapeutic functions have been recognized as a highly promising strategy for personalized nanomedicine. In this work, we synthesized a farnesylthiosalicylate (FTS, a nontoxic Ras antagonist) based triblock copolymer POEG-b-PVBA-b-PFTS (POVF) composed of a poly(oligo(ethylene glycol) methacrylate) (POEG) hydrophilic block, a poly(FTS) hydrophobic block, and a poly(4-vinylbenzyl azide) (PVBA) middle block. The POVF polymer itself was active in inhibiting the tumor growth in vitro and in vivo. Besides, it could serve as a carrier to effectively encapsulate paclitaxel (PTX) to form stable PTX/POVF mixed micelles with a diameter around 100 nm. Meanwhile, POVF polymer provides the active azide group for incorporating a positron emission tomography (PET) imaging modality via a facile strategy based on metal-free click chemistry. This nanocarrier system could not only be used for co-delivery of PTX and FTS, but also for PET imaging guided drug delivery. In the 4T1.2 tumor bearing mice, PET imaging showed rapid uptake and slow clearance of radiolabeled PTX/POVF nanomicelles in the tumor tissues. In addition, the FTS-based multi-functional nanocarrier was able to inhibit tumor growth effectively, and the co-delivery of PTX by the carrier further improved the therapeutic effect. STATEMENT OF SIGNIFICANCE: Due to the intrinsic heterogeneity of cancer and variability in individual patient response, personalized nanomedicine based on multi-functional carriers that integrate the functionalities of combination therapy and imaging guidance is highly demanded. Here we developed a multi-functional nanocarrier based on triblock copolymer POEG-b-PVBA-b-PFTS (POVF), which could not only be used for co-delivery of anticancer drugs PTX and Ras inhibitor FTS, but also for PET imaging guided drug delivery. The POVF carrier itself was active in inhibiting the tumor growth in vitro and in vivo. Besides, it was effective in formulating PTX with high drug loading capacity, which further enhanced the tumor inhibition effect. Meanwhile, we developed a simple and universal approach to incorporate a PET radioisotope (Zr-89 and Cu-64) into the azide-containing PTX/POVF micelles via metal-free click chemistry in aqueous solution. The radiolabeled PTX/POVF micelles exhibited excellent serum stability, rapid tumor uptake and slow clearance, which validated the feasibility of the PET image-guided delivery of PTX/POVF micelles.