The Effect of Unintended Facet Arthrodesis on the Treatment Outcome of Dynamic Neutralization System for Lumbar Degenerative Diseases.

Purpose: This study aimed to examine the influence of unintended facet arthrodesis on the therapeutic effectiveness of the dynamic neutralization system (Dynesys). Methods: This retrospective study enrolled consecutive patients who underwent posterior decompression and dynamic stabilization for lumbar spondylosis or spinal stenosis. Follow-up assessments included lumbar radiography, lumbar vertebral computerized tomography (CT), visual analog scale (VAS), and Oswestry disability index (ODI). Patients were classified into the facet fusion and non-fusion groups. The differences in the VAS scores for back pain and leg pain, ODI, intervertebral range of motion (ROM) at the surgical segments, and upper adjacent segments were assessed before and after treatment. Results: A total of 49 patients (29 males and 20 females) aged 31-65 years were enrolled and followed-up for over 40 months. Among the patients, 16 (32.7%) experienced unintended facet arthrodesis and were assigned to the fusion group, whereas the remaining patients were assigned to the non-fusion group. There was a significant increase in the incidence of facet arthrodesis in the surgical segments over time post-surgery (χ2 = 6.2, p < 0.05). The ROM of the surgical and upper adjacent segments, VAS scores for back pain and leg pain, and ODI were all significantly different before and after the operation (p < 0.05), but not between the fusion and non-fusion groups (p > 0.05). Conclusion: Although unintended facet arthrodesis is common after Dynesys procedure, the presence of facet arthrodesis does not significantly affect the efficacy of Dynesys in treating lumbar degenerative diseases.

Ultrasound high-definition microvasculature imaging with novel quantitative biomarkers improves breast cancer detection accuracy.

OBJECTIVES: To overcome the limitations of power Doppler in imaging angiogenesis, we sought to develop and investigate new quantitative biomarkers of a contrast-free ultrasound microvasculature imaging technique for differentiation of benign from malignant pathologies of breast lesion. METHODS: In this prospective study, a new high-definition microvasculature imaging (HDMI) was tested on 521 patients with 527 ultrasound-identified suspicious breast masses indicated for biopsy. Four new morphological features of tumor microvessels, microvessel fractal dimension (mvFD), Murray's deviation (MD), bifurcation angle (BA), and spatial vascularity pattern (SVP) as well as initial biomarkers were extracted and analyzed, and the results correlated with pathology. Multivariable logistic regression analysis was used to study the performance of different prediction models, initial biomarkers, new biomarkers, and combined new and initial biomarkers in differentiating benign from malignant lesions. RESULTS: The new HDMI biomarkers, mvFD, BA, MD, and SVP, were statistically significantly different in malignant and benign lesions, regardless of tumor size. Sensitivity and specificity of the new biomarkers in lesions > 20 mm were 95.6% and 100%, respectively. Combining the new and initial biomarkers together showed an AUC, sensitivity, and specificity of 97% (95% CI: 95-98%), 93.8%, and 89.2%, respectively, for all lesions regardless of mass size. The classification was further improved by adding the Breast Imaging Reporting and Data System (BI-RADS) score to the prediction model, showing an AUC, sensitivity, and specificity of 97% (95% CI: 95-98%), 93.8%, and 89.2%, respectively. CONCLUSION: The addition of new quantitative HDMI biomarkers significantly improved the accuracy in breast lesion characterization when used as a complementary imaging tool to the conventional ultrasound. KEY POINTS: • Novel quantitative biomarkers extracted from tumor microvessel images increase the sensitivity and specificity in discriminating malignant from benign breast masses. • New HDMI biomarkers Murray's deviation, bifurcation angles, microvessel fractal dimension, and spatial vascularity pattern outperformed the initial biomarkers. • The addition of BI-RADS scores based on US descriptors to the multivariable analysis using all biomarkers remarkably increased the sensitivity, specificity, and AUC in all size groups.

Soluble epoxide hydrolase inhibitor can protect the femoral head against tobacco smoke exposure-induced osteonecrosis in spontaneously hypertensive rats.

Exposure to tobacco smoke (TS) has been considered a risk factor for osteonecrosis of the femoral head (ONFH). Soluble epoxide hydrolase inhibitors (sEHIs) have been found to reduce inflammation and oxidative stress in a variety of pathologies. This study was designed to assess the effect of sEHI on the development of ONFH phenotypes induced by TS exposure in spontaneously hypertensive (SH) rats. SH and normotensive Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or TS (80 mg/m3 particulate concentration) 6 h/day, 3 days/week for 8 weeks. During this period, sEHI was delivered through drinking water at a concentration of 6 mg/L. Histology, immunohistochemistry, and micro-CT morphometry were performed for phenotypic evaluation. As results, TS exposure induced significant increases in adipocyte area, bone specific surface (BS/BV), and trabecular separation (Tb.SP), as well as significant decreases in bone mineral density (BMD), percent trabecular area (Tb.Ar), HIF-1a expression, bone volume fraction (BV/TV), trabecular numbers (Tb.N), and trabecular thickness (Tb.Th) in both SH and WKY rats. However, the protective effects of sEHI were mainly observed in TS-exposed SH rats, specifically in the density of osteocytes, BMD, Tb.Ar, HIF-1a expression, BV/TV, BS/BV, Tb.N, and Tb.SP. Our study confirms that TS exposure can induce ONFH especially in SH rats, and suggests that sEHI therapy may protect against TS exposure-induced osteonecrotic changes in the femoral head.

Comparing deep learning-based automatic segmentation of breast masses to expert interobserver variability in ultrasound imaging.

Deep learning is a powerful tool that became practical in 2008, harnessing the power of Graphic Processing Unites, and has developed rapidly in image, video, and natural language processing. There are ongoing developments in the application of deep learning to medical data for a variety of tasks across multiple imaging modalities. The reliability and repeatability of deep learning techniques are of utmost importance if deep learning can be considered a tool for assisting experts, including physicians, radiologists, and sonographers. Owing to the high costs of labeling data, deep learning models are often evaluated against one expert, and it is unknown if any errors fall within a clinically acceptable range. Ultrasound is a commonly used imaging modality for breast cancer screening processes and for visually estimating risk using the Breast Imaging Reporting and Data System score. This process is highly dependent on the skills and experience of the sonographers and radiologists, thereby leading to interobserver variability and interpretation. For these reasons, we propose an interobserver reliability study comparing the performance of a current top-performing deep learning segmentation model against three experts who manually segmented suspicious breast lesions in clinical ultrasound (US) images. We pretrained the model using a US thyroid segmentation dataset with 455 patients and 50,993 images, and trained the model using a US breast segmentation dataset with 733 patients and 29,884 images. We found a mean Fleiss kappa value of 0.78 for the performance of three experts in breast mass segmentation compared to a mean Fleiss kappa value of 0.79 for the performance of experts and the optimized deep learning model.

Quantitative Biomarkers for Cancer Detection Using Contrast-Free Ultrasound High-Definition Microvessel Imaging: Fractal Dimension, Murray's Deviation, Bifurcation Angle & Spatial Vascularity Pattern.

A growing body of evidence indicates that there is a strong correlation between microvascular morphological features and malignant tumors. Therefore, quantification of these features might allow more accurate differentiation of benign and malignant tumors. The main objective of this research project is to improve the quantification of microvascular networks depicted in contrast-free ultrasound microvessel images. To achieve this goal, a new series of quantitative microvessel morphological parameters are introduced for differentiation of breast masses using contrast-free ultrasound-based high-definition microvessel imaging (HDMI). Using HDMI, we quantified and analyzed four new parameters: 1) microvessel fractal dimension (mvFD), a marker of tumor microvascular complexity; 2) Murray's deviation (MD), the diameter mismatch, defined as the deviation from Murray's law; 3) bifurcation angle (BA), abnormally decreased angle; and 4) spatial vascular pattern (SVP), indicating tumor vascular distribution pattern, either intratumoral or peritumoral. The new biomarkers have been tested on 60 patients with breast masses. Validation of the feature's extraction algorithm was performed using a synthetic data set. All the proposed parameters had the power to discriminate the breast lesion malignancy (p < 0.05), displaying BA as the most sensitive test, with a sensitivity of 90.6%, and mvFD as the most specific test, with a specificity of 92%. The results of all four new biomarkers showed an AUC = 0.889, sensitivity of 80% and specificity of 91.4% In conclusion, the added value of the proposed quantitative morphological parameters, as new biomarkers of angiogenesis within breast masses, paves the way for more accurate breast cancer detection with higher specificity.

Identification of cell-free DNA methylation patterns unique to the human left ventricle as a potential indicator of acute cellular rejection.

Increased levels of donor-derived cell-free DNA (dd-cfDNA) in recipient plasma have been associated with rejection after transplantation. DNA sequence differences have been used to distinguish between donor and recipient, but epigenetic differences could also potentially identify dd-cfDNA. This pilot study aimed to identify ventricle-specific differentially methylated regions of DNA (DMRs) that could be detected in cfDNA. We identified 24 ventricle-specific DMRs and chose two for further study, one on chromosome 9 and one on chromosome 12. The specificity of both DMRs for the left ventricle was confirmed using genomic DNA from multiple human tissues. Serial matched samples of myocardium (n = 33) and plasma (n = 24) were collected from stable adult heart transplant recipients undergoing routine endomyocardial biopsy for rejection surveillance. Plasma DMR levels increased with biopsy-proven rejection grade for individual patients. Mean cellular apoptosis in biopsy samples increased significantly with rejection severity (2.4%, 4.4% and 10.0% for ACR 0R, 1R, and 2R, respectively) but did not show a consistent relationship with DMR levels. We identified multiple DNA methylation patterns unique to the human ventricle and conclude that epigenetic differences in cfDNA populations represent a promising alternative strategy for the non-invasive detection of rejection.

Another Whipple's triad? Pericardial, myocardial and valvular disease in an unusual case presentation from a Canadian perspective.

BACKGROUND: Whipple's disease is a clinically relevant multi-system disorder that is often undiagnosed given its elusive nature. We present an atypical case of Whipple's disease involving pan-valvular endocarditis and constrictive pericarditis, requiring cardiac intervention. A literature review was also performed assessing the prevalence of atypical cases of Whipple's disease. CASE PRESENTATION: A previously healthy 56-year-old male presented with a four-year history of congestive heart failure with weight loss and fatigue. Notably, he had absent gastrointestinal symptoms. He went on to develop pan-valvular endocarditis and constrictive pericarditis requiring urgent cardiac surgery. A clinical diagnosis of Whipple's disease was suspected, prompting duodenal biopsy sampling which was unremarkable, Subsequently, Tropheryma whipplei was identified by 16S rDNA PCR on the cardiac valvular tissue. He underwent prolonged antibiotic therapy with recovery of symptoms. CONCLUSIONS: Our study reports the first known case of Whipple's disease involving pan-valvular endocarditis and constrictive pericarditis. A literature review also highlights this presentation of atypical Whipple's with limited gastrointestinal manifestations. Duodenal involvement was limited and the gold standard of biopsy was not contributory. We also highlight the Canadian epidemiology of the disease from 2012 to 2016 with an approximate 4% prevalence rate amongst submitted samples. Routine investigations for Whipple's disease, including duodenal biopsy, in this case may have missed the diagnosis. A high degree of suspicion was critical for diagnosis of unusual manifestations of Whipple's disease.

In Situ SERS Detection of Photocatalytic Degradation of Aminothiophenol on Carbon-Nanotubes/CoPt Hollow Nanoparticles Composite.

The phenol derivatives, as one kind of hormone, are analogous to endocrine disruptors with high carcinogenicity. The photocatalytic technology is an effective approach to mitigate environmental pollution by utilizing solar energy to degrade organic pollutants. In this work, CoPt hollow nanoparticles (NPs) attached to carbon nanotubes (CNTs) are employed to catalytically decompose the p-aminothiophenol (PATP) molecules under light irradiation, which is monitored by using surface-enhanced Raman scattering spectra. The effect of temperature on the catalytic efficacy of CoPt hollow NPs is investigated. Moreover, the use of CNTs coating on CoPt NPs is found to accelerate the photocatalytic degradation rate of PATP molecules, attributed to the enhanced plasmon-exciton coupling interaction of the CoPt/CNTs hybrid configuration.

Acute Decompensated Heart Failure After Initiation of Amiodarone in a Patient With Anderson-Fabry Disease.

A 54-year-old man with the lysosomal storage disorder Anderson-Fabry disease (AFD) and cardiac involvement was placed on amiodarone for treatment of symptomatic paroxysmal atrial fibrillation. Shortly thereafter, he developed symptoms of acute decompensated heart failure, requiring hospital admission. Endomyocardial biopsy demonstrated findings consistent with AFD and possible amiodarone toxicity. Amiodarone was discontinued, and the patient's heart failure resolved with return to baseline status. Amiodarone is known to alter lysosomal pH and enzyme activity, and this case illustrates how it should be used with considerable caution in patients with AFD.

The lncRNA HNF1A-AS1 is a negative prognostic factor and promotes tumorigenesis in osteosarcoma.

Recent studies have revealed that long noncoding RNA HNF1A-antisense 1 (HNF1A-AS1) plays an important role in the development of several human malignancy entities. However, the expression and function of HNF1A-AS1 in the carcinogenesis and development of osteosarcoma remains unknown. In this study, we detected the HNF1A-AS1 levels in human osteosarcoma tissues and cell lines by quantitative real-time polymerase chain reaction (qRT-PCR), and investigated its role in osteosarcoma by using in vitro assays. Our study showed that HNF1A-AS1 expression was significantly up-regulated in human osteosarcoma tissues and cell lines compared with their normal counterparts, and its expression level was positively correlated with the distance metastasis (P = 0.009) and tumour stage (P = 0.019). Moreover, Kaplan-Meier curves with the log-rank test showed that higher expression of HNF1A-AS1 conferred a significantly poorer survival and multivariate Cox proportional hazards analysis revealed that HNF1A-AS1 was an independent risk factor of overall survival. In addition, the expression of HNF1A-AS1 in serum is correlated with patients' status and receiver operating characteristic (ROC) curve analysis demonstrated that HNF1A-AS1 could distinguish patients with osteosarcoma from healthy individuals (the area under curve 0.849, P < 0.001). Furthermore, in vitro knockdown of HNF1A-AS1 by siRNA significantly inhibited cell proliferation and G1 /S transition, and suppressed migration and invasion by reducing the epithelial-mesenchymal transition (EMT) program in osteosarcoma cells. Taken together, our data suggested that HNF1A-AS1 is a novel molecule involved in osteosarcoma progression, which may provide as a potential diagnostic, prognostic biomarker and therapeutic target.

Early Detection of Tibial Cartilage Degradation and Cancellous Bone Loss in an Ovariectomized Rat Model.

This study aimed to investigate degradation of the articular cartilage and loss of the cancellous bone in an ovariectomized (OVX) rat model simulating early human menopausal stage. Fourteen health female Sprague-Dawley rats were randomly divided into two groups (n = 7 per group): an OVX group that underwent bilateral ovariectomy to create an OVX model with low estrogen levels and a sham group in which only the periovarian fatty tissue was exteriorized. All the animals were sacrificed at 3 weeks after ovariectomy. The left tibiae were harvested. The articular cartilage at medial tibial plateau (MTP) and lateral tibial plateau (LTP) was assessed with quantitative high-frequency ultrasound. The cancellous bone was evaluated with micro-CT. The results indicated that, in comparison with the sham rats, the OVX rats exhibited significant alterations in acoustic parameters of the articular cartilage but insignificant changes in microarchitectural parameters of the cancellous bone in early stage of low estrogen levels. The results of this study suggest that cartilage degradation induced by estrogen reduction was detected earlier with quantitative ultrasound than that of the cancellous bone loss in 3 wk OVX rats.

Quantitative Ultrasound Assessment of Cartilage Degeneration in Ovariectomized Rats with Low Estrogen Levels.

The aim of this study was to assess quantitatively the site-specific degeneration of articular cartilage in ovariectomized rats with low estrogen levels using a high-frequency ultrasound system. Fourteen female Sprague-Dawley rats were randomly divided into two groups (n = 7 per group): a sham group in which only the peri-ovarian fatty tissue was exteriorized and an ovariectomized group that underwent bilateral ovariectomy to create a menopause model with low estrogen levels. All animals were sacrificed at the end of the third week after ovariectomy. Hindlimbs were harvested. The articular cartilage from five anatomic sites (i.e., femoral caput [FC], medial femoral condyle [MFC], lateral femoral condyle [LFC], medial tibial plateau [MTP] and lateral tibial plateau [LTP]) was examined with ultrasound. Four parameters were extracted from the ultrasound radiofrequency data: reflection coefficient of the cartilage surface (RC1), reflection coefficient of the cartilage-bone interface (RC2), ultrasound roughness index (URI) and thickness of the cartilage tissue. The results indicated significant (p < 0.05) site dependence for cartilage thickness, URI and RC1 in the sham group. The 3-wk post-menopause ovariectomized rats exhibited significant increases (p < 0.05) in the URI at the LFC, MTP and LTP; significant decreases (p < 0.05) in RC1 at the FC, LFC and MTP; and significant decreases (p < 0.05) in cartilage thickness at the MFC, LFC, MTP and LTP. These results of this study suggest that post-menopausal estrogen reduction induces morphologic and acoustic alterations in the articular cartilage of the hip and knee joints in ovariectomized rats.

Atypical squamous cells in the urine revealing endometrioid adenocarcinoma of the endometrium with squamous cell differentiation: a case report.

Urine cytology is mainly used to detect urothelial carcinoma (UC), especially for high-grade lesions including urothelial carcinoma in situ. Benign squamous cells are often seen in the urine specimens of women, they are either exfoliated from the trigone area of the bladder, the urethra, or the cervicovaginal region. However, abnormal squamous cells in the urine raise concerns of abnormalities of the urinary tract and cervicovaginal area which range from squamous metaplasia of the urothelium, a cervicovaginal squamous intraepithelial lesion, condyloma acuminatum of the bladder, UC with squamous differentiation, and squamous cell carcinoma. We present here a unique case of atypical squamous cells (ASCs) in the urine subsequently leading to the diagnosis of endometrioid adenocarcinoma of the endometrium with squamous differentiation. The presence of ASCs in voided urine is a rare finding that may indicate an underlying malignancy. Careful evaluation of squamous cells in the urine is an important part of our daily cytopathology practice.

Magnetic nanoparticles with a pH-sheddable layer for antitumor drug delivery.

A dually responsive nanocarrier with a multilayer core-shell architecture was prepared based on Fe3O4@SiO2 nanoparticles successively coated with poly(benzyl L-aspartate) (PBLA) and poly(ethylene glycol) (PEG) for the purpose of tumor specific drug delivery applications. In this system, PEG chains are connected to the surface via pH-sensitive benzoic-imine bonds and serve as a pH-sheddable hydrophilic corona. Meanwhile, the PBLA segments serve as a hydrophobic middle layer used to load the drugs via hydrophobic interactions. The Fe3O4@SiO2 nanoparticle functions as a superparamagnetic core used to direct the drug loaded nanocarrier to the target pathological site. The obtained materials were characterized with FT-IR, (1)H NMR, dynamic light scattering, zeta-potential, TEM, TGA, and hysteresis loop analysis. An anticancer drug doxorubicin (DOX) was selected as the model drug loaded into the nanocarrier, which was relatively stable under physiological conditions due to its neutral hydrophilic shell, and could quickly release the drug in response to increased acidity via shedding of the PEG shells through cleavage of the intermediate benzoic-imine bonds. Meanwhile, the neutral shell shedding would reveal a positively charged nanoparticle surface that is readily taken up by tumor cells. These pH- and magnetic-responsive nanoparticles showed significant potential for use in the targeted intracellular delivery of hydrophobic chemotherapeutics in cancer therapy.

Controlled release of protein from biodegradable multi-sensitive injectable poly(ether-urethane) hydrogel.

The synthesis and characterization of multi-sensitive polymers for use as injectable hydrogels for controlled protein/drug delivery is reported. A series of biodegradable multi-sensitive poly(ether-urethane)s were prepared through a simple one-pot condensation of poly(ethylene glycol), 2,2'-dithiodiethanol, N-methyldiethanolamine, and hexamethylene diisocyanate. The sol-gel phase transition behaviors of the obtained copolymers were investigated. Experimental results showed that the aqueous medium comprising the multi-segment copolymers underwent a sol-to-gel phase transition with increasing temperature and pH. At a certain concentration, the copolymer solution could immediately change to a gel under physiological conditions (37 °C and pH 7.4), indicating their suitability as in situ injectable hydrogels in vivo. Insulin was used as a model protein drug for evaluation of the injectable hydrogels as a site-specific drug delivery system. The controlled release of insulin from the hydrogel devices was demonstrated by degradation of the copolymer, which is modulated via the 2,2'-dithiodiethanol content in the poly(ether-urethane)s. These hydrogels having multi-responsive properties may prove to be promising candidates for injectable and controllable protein drug delivery devices.

An injectable and biodegradable hydrogel based on poly(α,ß-aspartic acid) derivatives for localized drug delivery.

An injectable hydrogel via hydrazone cross-linking was prepared under mild conditions without addition of cross-linker or catalyst. Hydrazine and aldehyde modified poly(aspartic acid)s were used as two gel precursors. Both of them are water-soluble and biodegradable polymers with a protein-like structure, and obtained by aminolysis reaction of polysuccinimide. The latter can be prepared by thermal polycondensation of aspartic acid. Hydrogels were prepared in PBS solution and characterized by different methods including gel content and swelling, Fourier transformed-infrared spectroscopy, and in vitro degradation experiment. A scanning electron microscope viewed the interior morphology of the obtained hydrogels, which showed porous three-dimensional structures. Different porous sizes were present, which could be well controlled by the degree of aldehyde substitution in precursor poly(aspartic acid) derivatives. The doxorubicin-loaded hydrogels were prepared and showed a pH-sensitive release profile. The release rate can be accelerated by decreasing the environmental pH from a physiological to a weak acidic condition. Moreover, the cell adhesion and growth behaviors on the hydrogel were studied and the polymeric hydrogel showed good biocompatibility.

Synthesis, characterization and controlled drug release from temperature-responsive poly(ether-urethane) particles based on PEG-diisocyanates and aliphatic diols.

A series of linear amphiphilic poly(ether-urethane)s with alternative hydrophilic/hydrophobic segments based on PEG-diisocyanates and aliphatic diols is developed. The molecular structures of the copolymers were confirmed with nuclear magnetic resonance, Fourier transform infrared spectra and gel permeation chromatography. Nanoparticles prepared by self-assembly of the resulting copolymers show sharp temperature-responsive phase transition. The phase transition temperature could be easily modulated by the length of hydrophilic or hydrophobic segments of the polymer. The mechanism of the temperature-responsive behaviour is discussed. In the presence of these obtained poly(ether-urethane)s, doxorubicin (DOX) could be dispersed into aqueous solution. The ratio of DOX release from polymeric particles increased sharply above the phase transition temperature, while the release was suppressed below the phase transition temperature. A controlled drug release can be achieved by changing the environmental temperature. The easy-prepared polymeric nanoparticles, with features of biocompatibility, biodegradability and tail-made temperature responsiveness, are a kind of promising carriers for temperature-controllable drug release.

Layer-by-layer assembled polyaspartamide nanocapsules for pH-responsive protein delivery.

Biodegradable shell cross-linked nanocapsules were prepared via layer-by-layer assembly of PADH (tertiary amine and hydrazide grafted polyaspartamide) and PACA (carboxyl and aldehyde grafted polyaspartamide) on silica spheres. Both of the polyaspartamide derivatives are water-soluble and biodegradable polymers with a protein-like structure, and obtained by aminolysis reaction of polysuccinimide. The latter is prepared by thermal polycondensation of aspartic acid. Dynamic light scattering and zeta potential measurements were used to analyze the layer-by-layer assembly process. Bovine serum albumin (BSA), as a model protein, was entrapped in the nanocapsules via electrostatic adsorption. Nanocapsules encapsulating BSA were prepared via layer-by-layer assembly on protein-entrapping amino-functionalized silica spheres, hydrazone cross-linking and silica core removal. The BSA release profiles exhibited a pH-dependent behavior. BSA release rate increased significantly as the ambient pH dropped from the physiological pH to acidic. Cell viability study suggests that the obtained polymeric nanocapsules have good biocompatibility. These kinds of novel composite nanocapsules may offer a promising delivery system for proteins.

Layer-by-layer supramolecular assemblies based on linear and star-shaped poly(glycerol methacrylate)s for doxorubicin delivery.

Hollow microcapsules, composed of pH responsive polyelectrolytes via a layer-by-layer (LBL) adsorption technique, were prepared. Linear or star-shaped poly(glycerol metha crylate)s (PGOHMAs) modified with 1,4-butanediamine and 1,2-ethanediamine (EDA) were synthesized and used as polycations. Poly(acrylic acid) was employed as polyanion and SiO2 (about 170 nm) as template. After LBL absorption, SiO2 cores were removed by HF treatment. The particle size and zeta potential were measured by dynamic light scattering, showing that the diameter of star-shaped amino-PGOHMA was larger than linear counterpart. The LBL assembly and core-etching process were evidenced by scanning electron microscope, transmission electron microscope, and energy dispersive spectrometer. The cytotoxicity experiments on human umbilical vein endothelial cells were carried out to evaluate the toxicity of LBL assembly. The star-shaped and EDA-modified PGOHMA exhibited better cell viability. The microcapsules were then used to load an anticancer drug, doxorubicin hydrochloride. High loading capacity (about 42%) and entrapment efficiency (84%) were obtained for star-shaped polymer-based microcapsules. The cumulative release rate was evaluated in vitro, showing faster release at an acidic condition compared to neutral pH. Confocal laser scanning microscopy evidenced the successful cellular uptake of DOX-loaded microparticles.

Temperature- and pH-responsive nanoparticles of biocompatible polyurethanes for doxorubicin delivery.

A series of temperature- and pH-responsive polyurethanes based on hexamethylene diisocyanate (HDI) and 4,4'-diphenylmethane diisocyanate (MDI) were synthesized by a coupling reaction with bis-1,4-(hydroxyethyl) piperazine (HEP), N-methyldiethanolamine (MDEA) and N-butyldiethanolamine (BDEA), respectively. The chemical structure, molecular weight, thermal property and crystallization properties were characterized by Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) spectroscopy. The resulting polyurethanes were then used to prepare nanoparticles either by direct dispersion method or dialysis method. Their pH and temperature responsibilities were evaluated by optical transmittance and size measurement in aqueous media. Interestingly, HDI-based and MDI-based polyurethanes exhibited different pH and temperature responsive properties. Nanoparticles based on HDI-HEP and HDI-MDEA were temperature-responsive, while MDI-based biomaterials were not. All of them showed pH-sensitive behavior. The possible responsive mechanism was investigated by (1)H NMR spectroscopy. The cytotoxicity of the polyurethanes was evaluated using methylthiazoletetrazolium (MTT) assay in vitro. It was shown that the HDI-based polyurethanes were non-toxic, and could be applied to doxorubicin (DOX) encapsulation. The experimental results indicated that DOX could be efficiently encapsulated into polyurethane nanoparticles and uptaken by Huh-7 cells. The loaded DOX molecules could be released from the drug-loaded polyurethane nanoparticles upon pH and temperature changes, responsively.