Jintian Tang

Pharmaceutical nanotechnology for oral delivery of anticancer drugs

Oral chemotherapy is an important topic in the 21st century medicine, which may radically change the current regimen of chemotherapy and greatly improve the quality of life of the patients. Unfortunately, most anticancer drugs, especially those of high therapeutic efficacy such as paclitaxel and docetaxel, are not orally bioavailable due to the gastrointestinal (GI) drug barrier. The molecular basis of the GI barrier has been found mainly due to the multidrug efflux proteins, i.e. P-type glycoproteins (P-gp), which are rich in the epithelial cell membranes in the GI tract. Medical solution for oral chemotherapy is to apply P-gp inhibitors such as cyclosporine A, which, however, suppress the bodys immune system either, thus causing medical complication. Pharmaceutical nanotechnology, which is to apply and further develop nanotechnology to solve the problems in drug delivery, may provide a better solution and thus change the way we make drug and the way we take drug. This review is focused on the problems encountered in oral chemotherapy and the pharmaceutical nanotechnology solutions such as prodrugs, nanoemulsions, dendrimers, micelles, liposomes, solid lipid nanoparticles and nanoparticles of biodegradable polymers. Proof-of-concept in vitro and in vivo results for oral delivery of anticancer drugs by the various nanocarriers, which can be found so far from the literature, are provided.

Enhancement characteristics of benign and malignant focal peripheral nodules in the peripheral zone of the prostate gland studied using contrast-enhanced transrectal ultrasound

AIM To assess the value of contrast-enhanced grey-scale transrectal ultrasound (CETRUS) in predicting the nature of peripheral zone hypoechoic lesions of the prostate. MATERIALS AND METHODS Ninety-one patients with peripheral zone hypoechoic lesions on ultrasound were evaluated with CETRUS followed by lesion-specific and sextant transrectal ultrasound-guided biopsies. The enhancement patterns of the lesions were observed and graded subjectively using adjacent peripheral zone tissue as the reference. Time to enhancement (AT), time to peak intensity (TTP) and peak intensity (PI) were quantified within each nodule. Ultrasound findings were correlated with biopsy findings. RESULTS Transrectal ultrasound-guided biopsy of the hypoechoic lesions revealed prostate cancer in 44 patients and benign prostatic diseases in 47. The intensity of enhancement within the lesions were graded as no enhancement, increased, equal, or decreased compared with adjacent peripheral zone tissue in two, 30, five and seven in the prostate cancer group and 14, 15, four and 14 in the benign group, respectively. The difference was statistically significant (p<0.05). The peak enhancement intensity was found to be the most optimal discriminatory parameter (area under curve AUC 0.70; 95% CI: 0.58, 0.82). CONCLUSION Malignant hypoechoic nodules in the peripheral zone of the prostate are more likely to enhance early and more intensely on CETRUS. A non-enhanced hypoechoic peripheral zone lesion was more likely to be benign.

Nanomedicine for oral chemotherapy

Oral chemotherapy is one of the most important issues in 21st century medicine. It may radically change the current regimen of chemotherapy, as well as greatly improve the quality of life of patients. In comparison with the current practice of chemotherapy (i.e., intravenous injection or infusion), which causes high peak above the maximum tolerable drug concentration in the plasma and fast excretion of the drug from the circulatory system, oral chemotherapy can maintain a sustained and mild drug concentration in the circulation to achieve a prolonged exposure of cancerous cells to the drug. This will increase the therapeutic efficacy and decrease the side effects. Moreover, oral chemotherapy is an important step to realize the patients’ dream of ‘chemotherapy at home’, which will greatly improve their quality of life and give hope to those with late-stage cancer, who have been too weak to tolerate any treatment in the current clinical regimen. Oral chemotherapy provides at least a palliative treatment to give them hope and extend their life [1]. Unfortunately, most anticancer drugs, especially those with excellent anticancer effects such as taxanes (paclitaxel and docetaxel), are not orally bioavailable (i.e., not absorbable/interactive in the GI tract). For paclitaxel, for example, the initial studies reported that its oral bioavailability was less than 1% [2]. As we know, our body is so perfectly structured that all important organs are protected from external toxins by the so-called physiological drug barriers, such as the blood–brain barrier and the gastrointestinal (GI) barrier. The molecular basis of the various physiological drug barriers had been unknown until the past decade when understanding of the molecular biology has made significant progress. For oral bioavailability of taxanes, which are the number one seller among the various anticancer drugs and had US

Abnormal DNA methylation in peripheral blood mononuclear cells from patients with vitiligo

3.6 billion annual sale in 2006 in

Effect of hyperthermia on the apoptosis and proliferation of CaSki cells

Background  Vitiligo is a skin disorder characterized by the destruction of melanocytes by autoreactive lymphocytes. The genetic and environmental factors that trigger the autoimmune response are poorly understood. However, alterations to epigenetic DNA methylation patterns contribute to many other autoimmune diseases.

Induction Heating of Magnetic Fluids for Hyperthermia Treatment

Hyperthermia is a promising treatment for human cervical cancer. However, little is known about whether and under what conditions heat treatment exerts tumor inhibition effects on cervical cancer, and the molecular mechanisms behind these cellular responses have yet to be elucidated. We employed the human cervical cancer cell line CaSki as a cellular model and examined the effect of cell apoptosis and proliferation under gradient thermal conditions (43, 45 and 47˚C for 40 min). Heat treatment was found to induce CaSki cell apoptosis and necrosis. Cell cycle analysis showed that cells were arrested in S phase upon the application of hyperthermia, and MTT analysis revealed that cell viability was also reduced. Of the thermal conditions, 45˚C exhibited the best induction of apoptosis, while 47˚C induced direct fierce necrosis. This was further demonstrated by examining the expression level of several key apoptosis-related genes: caspase-3, Smac and Survivin. During apoptosis, caspase-3 and Smac levels were up-regulated, whereas anti-apoptotic Survivin was down-regulated, enhancing programmed cell death. Our results reveal that heating at ≥45˚C induced cell apoptosis and necrosis, and inhibited cell proliferation at both the cellular and molecular levels. These findings support the use of hyperthermia in a clinical setting for the treatment of human cervical cancer.

Folic acid-conjugated superparamagnetic iron oxide nanoparticles for tumor-targeting MR imaging.

The induction heating of magnetic fluids for magnetic induction hyperthermia treatments is theoretically analyzed, with regard to the influences by magnetic field parameters, material properties, and demagnetizing field effects in finite-size samples. A monodispersion model of noninteracting superparamagnetic particles, subjected to a magnetic field of the intensity hex < 16 kAm-1 and frequency f < 1 MHz, is used for the analysis. Calculation results show that the induction heating has a quasi-linear dependence on field intensity and a quasi-negative exponential dependence on field frequency. As for the influences by material parameters, respectively, the induction heating has a double-exponential-like dependence on the magnetic core size and a negative dependence on the coating layer thickness of the superparamagnetic particles. Similarly, the heating dependence on the carrier liquid viscosity is also a double-exponential-like relationship. Besides, the induction heating has a linear dependence on the volume fraction of the superparamagnetic particles, and a negative dependence on the demagnetizing factors, which are related to the sample shapes and orientations. Initial experiments are performed for validating the analytical calculation results.

A new prenylated indole diketopiperazine alkaloid from Eurotium cristatum.

Abstract Superparamagnetic iron oxide nanoparticles (SPIONs) have been the subject of extensive research due to their potential biomedical applications. In the present investigation, superparamagnetic FA-PEI-Fe3O4 were successfully prepared and evaluated as a targeted MRI contrast agent. FTIR characteristics, TGA, VSM, and MR imaging confirmed the composition and magnetic properties of the synthesized nanoparticles. TEM showed that FA-PEI-Fe3O4 were spherical in shape and well dispersed. The nanoparticles were superparamagnetic at room temperature with a saturation magnetization value of 67.1 emu/g. The nanoparticles showed higher uptake efficiency due to receptor-mediated endocytosis. Moreover, specificity of FA-PEI-Fe3O4 to target tumor cells was demonstrated by the increased nanoparticle uptake and significant contrast enhancement of KB cells over MCF7 cells. The competitive inhibition of FA-PEI-Fe3O4 by free FA further confirmed the specific interaction of this conjugate with FA receptors. In vivo MR imaging studies showed a decreased signal intensity and enhanced tumor contrast post-injection of FA-PEI-Fe3O4. These results indicate that FA-PEI-Fe3O4 can be used as a promising tumor-targeting agent as well as a T2 negative-contrast agent in MR imaging applications.

Effects of magnetic induction hyperthermia and radiotherapy alone or combined on a murine 4T1 metastatic breast cancer model.

A new prenylated indole diketopiperazine alkaloid, cristatumin F (1), and four known metabolites, echinulin (2), dehydroechinulin (3), neoechinulin A (4) and variecolorin O (5), were isolated from the crude extract of the fungus Eurotium cristatum. The structure of 1 was elucidated primarily by NMR and MS methods. The absolute configuration of 1 was assigned using Marfey’s method applied to its acid hydrolyzate. Cristatumin F (1) showed modest radical scavenging activity against DPPH radicals, and exhibited marginal attenuation of 3T3L1 pre-adipocytes.

Nanothermotherapy by high performance magnetic nanoparticles.

Purpose: The purpose of this study was to explore the effects of MIH and radiotherapy alone or combined on metastatic breast cancer and the underlying mechanisms. Materials and methods: A murine 4T1 metastatic breast cancer model was established and randomly assigned into four treatment groups: C (control), R (radiotherapy), MIH, and MIH + R. Tumour volume, lung metastasis, the expression of Bax and MMP-9, T cell subsets, serum cytokine levels, and mouse survival were evaluated. Results: Group MIH + R showed significantly reduced tumour volume, lung metastasis, improved survival and increased Bax expression compared to group R or MIH (P < 0.05). MMP-9 expression in the primary tumour tissue was significantly increased in group R compared to the other groups (P < 0.05), which could be brought down by combined MIH treatment. Group MIH + R showed significantly higher CD4+ T cell percentage as well as CD4+/CD8+ cell ratio than group R (P < 0.05). Group MIH + R showed significantly higher serum levels of TNF-α, IFN-γ and IL-2 than group R (P < 0.05). Conclusions: MIH not only promotes the tumour-cell killing effect of radiotherapy through Bax-mediated cell death, but also improves cellular immunity in mice under radiotherapy and decreases the potential of radiotherapy to enhance MMP-9 expression, which leads to significant improvement in lung metastasis and overall survival of mice under combined treatment of MIH and R. This study is the first to have explored the effect of combined hyperthermia and radiotherapy on tumour metastasis and the underlying mechanisms. It provides insights into the application of MIH as an adjuvant to radiotherapy for metastatic breast cancer.