China
Africa
Explore chapters and articles related to this topic
Nanomedicine(s) under the Microscope *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Cancer is a major focus for development of new drugs with ∼16,000 of the ∼40,000 clinical trials listed in 2009 dedicated to this topic (reviewed in Ref. [201]). Currently ∼70 cancer clinical trials are ongoing involving nanomedicines [202], many being follow-on indications and/or combinations of first-generation products. Technologies include liposomes [203–205], polymer conjugates [176, 177, 206] and block copolymer micelles [207–210], nanoparticles (e.g., Abraxane [211]), and nanosized crystals (e.g., 2-methoxyestradiol (2ME2) Nano-Crystal dispersion [212]). The goals have been improved formulation, tumor targeting by local administration [213, 214], passive targeting using the enhanced permeability and retention (EPR) effect [215] (e.g., Doxil [216], Opaxio [49]) or receptor-mediated targeting (e.g., Mylotarg [217, 218], HPMA copolymer-doxorubicin-galactose FCE28069 [132], Trastuzumab-DM1 [117]). Certain products also seek to promote cytosolic delivery (e.g., cyclodextrin polymer-based nanoparticle [219]) and overcome drug resistance and reduce chemotherapy side effects [185], as well as improve patient convenience (e.g., Neulasta [220]).
Environmental Toxins and Chronic Illness
Published in Aruna Bakhru, Nutrition and Integrative Medicine, 2018
One phase II methylation enzyme, in particular, has received much attention in the research and clinical communities because of its involvement in metabolism of estrogen metabolites that may promote breast cancer formation. During phase I metabolism estradiol (E2) is metabolized to the strongly procarcinogenic compound 4-hydroxy-estradiol (4-OH-E2) (Zhu, 2003). Fortunately, the adverse impact on health of this metabolite is greatly minimized by the phase II methylation enzyme catechol-O-methyltransferase (COMT), which converts 4-OH-E2 to the relatively inert O-methylated metabolite 4-methoxyestradiol (4-MeO-E2) (Zhu, 2003). However, the anticarcinogenic properties of COMT do not end here. COMT also converts 2-hydroxyestradiol (2-OH-E2) to 2-methoxyestradiol (2-MeO-E2) (Zhu, 2003). 2-MeO-E2 is associated with reduced cancer formation in several ways. First, it has little or no estrogen receptor-binding activity. Next, it may actually prevent cancer formation due to its antiproliferative, cytotoxic, and apoptotic actions (Zhu, 2002).
Nondegradable Intraocular Sustained-Release Drug Delivery Devices
Published in Glenn J. Jaffe, Paul Ashton, P. Andrew Pearson, Intraocular Drug Delivery, 2006
Mark T. Cahill, Glenn J. Jaffe
While a number of animal models of diabetic macular edema exist, sustained delivery of steroids using a nondegradable device has not been tested in an animal model (14,15). Other nondegradable sustained-release drugs that have been investigated in vitro but not in animal models, include methotrexate and trimetrexate to treat intraocular lymphoma, and disease 2-methoxyestradiol to treat choroidal neovascularization (16–18).
Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells
Published in Drug Delivery, 2022
Zuhier A. Awan, Shareefa A. AlGhamdi, Nabil A. Alhakamy, Solomon Z. Okbazghi, Mohamed A. Alfaleh, Shaimaa M. Badr-Eldin, Hibah M. Aldawsari, Mohammed A. S. Abourehab, Hani Z. Asfour, Shadi A. Zakai, Mohammad W. Alrabia, Aya A. Negm, Mohamed A. El-Moselhy, Sara S. Sharkawi, Waleed Y. Rizg
2-Methoxyestradiol (2ME, Figure 1(A)) is a naturally occurring metabolite of estrogen, with anti-proliferative and anti-angiogenic properties, which can help arrest the growth and potentially destroy cancer cells. 2ME shows zero estrogenic efficacy (Lee et al., 2008; Tevaarwerk et al., 2009). Its anti-cancer property stems from its ability to initiate apoptosis by inhibiting hypoxia-inducible factor 1 and activating p53 (Pillai et al., 2017). Certain studies have observed that 2ME binds to tubulin, thereby stopping mitosis by forming microtubule (Lakhani et al., 2003). A report deemed 2ME effective in fighting prostate cancer, although the plasma concentration of 2ME does not sustain for long (Sweeney et al., 2005). It was noted that a significantly high dose was required in human beings when administered orally; however, nano-2ME formulation shows enhanced pharmacokinetic properties in animal test subjects (Wang et al., 2011; Alhakamy et al., 2021).
Co-administration of paclitaxel and 2-methoxyestradiol using folate-conjugated human serum albumin nanoparticles for improving drug resistance and antitumor efficacy
Published in Pharmaceutical Development and Technology, 2021
Xinyang Liu, Taoqian Zhao, Yue Xu, Pengchao Huo, Xia Xu, Zhenzhong Zhang, Qingfeng Tian, Nan Zhang
Multidrug resistance (MDR) is another important issue for the failure of PTX to treat various types of cancers (Holohan et al. 2013; Iyer et al. 2013). The cancer patients are very sensitive to chemotherapeutic agent in the early stage, but resistance may occur in the later period of chemotherapy. MDR is often caused by the overexpression of active efflux transporters which export the anticancer drugs out of the cancer cells, and then reduces the intracellular concentration of drugs. The active efflux transporters includes DNA methyltransferase1 (DNMT1), P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-related protein 1 (MRP1) (Aller et al. 2009). Currently, many reports indicated the combination of a chemotherapeutic drug and chemosensitizer could improve the drug efficiency for the cancers drug resistance by inhibiting the drug efflux by P-gp (Chen et al. 2017; Zou et al. 2017), such as doxorubicin and curcumin (Wang et al. 2015), PTX and curcumin (Ganta and Amiji 2009), and PTX and quercetin (Kang et al. 2017). 2-methoxyestradiol (2-ME), a natural metabolite of estradiol (Hamel et al. 1996), could effectively overcome drug resistance in tumor cells. The co-administration of 2-ME with PTX has the better anticancer effect than PTX alone (Chauhan et al. 2002). Previous study showed the better effects of tumor inhibition by the combination of PTX and 2-ME (Han et al. 2005).
PEG-PCL modification and intestinal sustained-release of solid lipid nanoparticles for improving oral bioavailability of 2-methoxyestradiol
Published in Journal of Liposome Research, 2019
YaBing Xing, Xin Liu, Xiao Li, Fang Ding, JunYa Zhang, XinHong Guo
2-Methoxyestradiol (2-ME) has various biological effects including anti-inflammatory, anti-tumour, and anti-angiogenic effects. Because of its good tolerability and minimal toxic effects, the development of its oral formulations received more and more attention in the world all along (Dingli et al.2002, Sidor et al.2005). However clinical application of 2-ME through the oral route was hindered due to its poor aqueous solubility, obvious liver first pass effect, intestinal absorption saturation, and quick elimination (Ireson et al.2004, Sweeney et al.2005, Guo et al.2009). At present, its oral formulations such as tablets, capsule, and nanocrystal suspension (Panzem5® NCD) have been confirmed to be ineffective for all kinds of tumour therapy in Phase I and Phase II clinical trials (James et al.2007, Rajkumar et al.2007). Hence, a new formulation system that improves its oral bioavailability and prolongs its retention time in the body is required. However, there are few reports in this field (Cao 2014, Guo et al.2017).