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Controlled Release of Hormones by Pellet Implants
Published in Emmanuel Opara, Controlled Drug Delivery Systems, 2020
Any molecule that is capable of binding to androgen receptors (AR) and brings about the biological effect is termed as androgen. These compounds exhibit varying degrees of affinity towards AR, and the biological effects could be either positive or negative. Depending on the biological effect, the compound could be referred to as androgen or anti-androgen, or as androgen-receptor modulator (ARM). The use of androgen in laboratory animals or free-living field animals has been in practice in order to (i) test the preclinical therapeutic potentials or toxicity of androgens; (ii) study the influence of androgens on the behavioral changes or morphological change in the experimental animals (Hau 2007, Fusani 2008, Handelsman, Conway, and Boylan 1990, Jockenhovel et al. 1996, Kelleher, Conway, and Handelsman 2001, Kelleher et al. 2004, Quispe et al. 2015). Some of the available ARMs as S.C. sustained-release pellets are listed in Table 6.2:
Microwave-Assisted Synthesis and Functionalization of Six-Membered Oxygen Heterocycles
Published in Banik Bimal Krishna, Bandyopadhyay Debasish, Advances in Microwave Chemistry, 2018
Neha Batra, Rahul Panwar, Ramendra Pratap, Mahendra Nath
Chromenes are benzopyran analogs which form after the fusion of a benzene ring with a six-membered pyran ring. They exist in two isomeric forms such as 2H-chromenes (2H-1-benzopyrans) and 4H-chromenes (4H-1-benzopyrans). Among the chromenes, coumarins (2H-chromen-2-one) have received considerable attention due to their diverse pharmacological profiles such as anticoagulant [98], anticancer [99], anti-HIV [100], antitumor [101], anti-inflammatory [102], anti-Alzheimer′s [103], antileukemic [104], antibacterial [105], antimalarial [106], antitubercular [107], platelet antiaggregator [108], antioxidant [109], anti-HCV [110], hypoglycaemic [111], antifungal [112], and antifilarial agents [113]. The antitumor effect of coumarins is associated with the metabolite 7-hydroxycoumarin [114]. Coumarins are also associated with strong coronary vasodilating effects [115]. The structures of some of the biologically relevant coumarins are presented in Figure 9.2. LG120746 acts as progesterone receptor modulator [116], acolbifene used as estrogen receptor modulator [117], cannabinol exhibited affinity towards the CB1 and CB2 [118, 119] whereas moracin D has demonstrated fungicidal effect [120]. Besides these, coumarins are also used in cosmetics [121] and agrochemicals [122]. They are useful as dyes [123], sensors, and probes due to significant fluorescent properties [124]. Therefore, a large number of synthetic methods have been developed from time to time to construct these molecules for a variety of applications (Figure 5.2).
Tuning of Ruthenium – DMSO Complexes for Search of New Anticancer Agents
Published in Ajay Kumar Mishra, Lallan Mishra, Ruthenium Chemistry, 2018
NAMI-A is very well-studied ruthenium DMSO complex in clinical trials. It has also undergone phase I clinical trials and it was well tolerated in patients; reversible blister formation is the dose-limiting toxicity (Rademaker-Lakhai et al., 2004; Sava et al., 2002). NAMI-A coordinated with nucleic acids and directly affected the DNA of cancerous cells (Sava, 2004). It is documented that NAMI-A seems to be independent of direct cytotoxic effects but showed inhibitory effects in various types of primary tumors or metastases (Sava, 1999). Among Ru (III) complexes, NAMI-A is a leading compound that has the cooperative effects of anti-angiogenic and anti-invasive properties on tumor cells and blood vessels involving the inhibition of the processes of tumor invasiveness. The scavenging properties of NAMI-A influenced the NO produced by the endothelial cells probably control the angiogenesis in chick allantoic membrane (embryonic membrane) and the eye cornea model in rabbit (Vacca et al., 2002; Morbidelli et al., 2003). The molecular investigation showed that it blocks extracellular mitogen-activated protein kinase/mitogen and activates phosphokinase/extracellular signal-regulated kinase pathway in endothelial cells. This is probably due to the suppression of a membrane PKC (protein kinase C), leading to the arrest of c-myc transcription, capspase-3 activation, and apoptosis (Sanna, 2002). In view of anti-invasive effects, NAMI-A also reduces the spontaneous invasion of matrigel (gelatinous protein mixture) by tumor cells in a dose-dependent reduction of gelatinase release by the same cells and activation of adhesion molecules such as beta-integrins (Sava, 2004). According to further pharmacological studies, NAMI-A is also capable of changing cell shape or reduce metastases growth by combining to CD44 (cell membrane receptor modulator: cell surface glycoprotein involved in cell/cell and cell/matrix interactions) and tumor infiltrating lymphocyte recruitment (Pacor, 2004).
Alginate-coated chitosan nanoparticles for pH-dependent release of tamoxifen citrate
Published in Journal of Experimental Nanoscience, 2022
Muhammad Khurram Waqas, Shees Safdar, Manal Buabeid, Akram Ashames, Muhammad Akhtar, Ghulam Murtaza
Tamoxifen is a selective oestrogen receptor modulator (SERM) that is used to treat breast cancer for more than 20 years but it has some limitations due to its serious side effects and low solubility in the water [17]. The anti-estrogenic activity of the tamoxifen depends on location of the tissue and the concentration of the dose [18]. Tamoxifen shows good bioavailability upon oral administration and inhibit binding of oestradiol with the oestrogen receptor as a result oestrogen response is prevented [19]. Oral delivery of tamoxifen is achieved by using its tablets or solution at a dose of 10 mg twice a day [20]; however, it leads to extensive metabolism of tamoxifen in liver [21]. The oral bioavailability of tamoxifen could be enhanced by using its encapsulated formulations, such as microparticles and nanoparticles using suitable polymers. Few studies have already been conducted for the preparation of nanospheres using polyethylene glycol, nanoparticles using poly(-caprolactone), and poly lactide-co-glycolide microspheres. Moreover, chitosan features could also be improved by joining it with other polymers, such as alginate and hyaluronic acid [22].
Dendrimer as a promising nanocarrier for the delivery of doxorubicin as an anticancer therapeutics
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Vanshikha Singh, Prashant Kesharwani
Recently Li et al. developed a pH sensitive dual targeting nanocarrier (G4–DOX–PEG–Tf–TAM) with macromolecule transferrin peptide conjugated onto the exterior surface and drug tamoxifen (TAM) on the interior region of a G4 PAMAM dendrimers for targeting drug delivery to glioma cells. Transferrin (Tf) and TAM were linked to increase specificity and for accumulating the drug at targeted site. Transferrin is an endogenic cellular transport ligand which is extensively studied for targeting brain tumors since Tf receptor are widely expressed on brain capillary endothelial cells. Tamoxifen, an estrogen receptor modulator on the other hand is utilized for enhancing drug penetration into BBB by inhibiting multi-drug resistant proteins like breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), and MRP4 (ABCC4), which are expressed largely over glioma cells are responsible for suppressing the drug transportation across BBB. Altogether, the nanostructure was designed such that, it had seven DOX molecules of drug bonded via hydrazine bond, Tf and PEG (30 PEG1000 and PEG2000 chains) bound on the outer surface for specific targeting and increasing biocompatibility of DOX and 29 TAM molecules enclosed in the inner region serving as multi-drug resistant inhibitors. Different tests carried out for examining the properties of this conjugated dendrimer revealed that G4–DOX–PEG–Tf–TAM showed pH triggered release of drug, along with improved specificity and higher penetration rates (across BBB) as studied using BBB model and active aggregation of drug in the avascular C6 glioma spheroids thereby inducing cell death and tumor reduction. Collectively, this research suggests a potential use of dual-targeting nanocarrier (G4–DOX–PEG–Tf–TAM) for treating brain tumors more effectively [95].
Overview of biological mechanisms of human carcinogens
Published in Journal of Toxicology and Environmental Health, Part B, 2019
Nicholas Birkett, Mustafa Al-Zoughool, Michael Bird, Robert A. Baan, Jan Zielinski, Daniel Krewski
There is supporting evidence for a non-genotoxic pathway for tamoxifen-induced carcinogenesis in humans. Tamoxifen is a selective estrogen-receptor modulator. In the endometrial endothelium, this drug acts as an agonist, stimulating cellular proliferation. Evidence suggests that the genes targeted by tamoxifen activation of the estrogen receptor differ from those stimulated by estrogen itself. This mechanism may be responsible for the differential action of tamoxifen in distinct tissues, and may contribute to carcinogenicity.