Repositioning of Anti-parasitic Drugs in Cyclodextrin Inclusion Complexes for Treatment of Triple-Negative Breast Cancer

Abstract

This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com". Abstract.Drug repositioning refers to the identification of new therapeutic indications for drugs already approved. Albendazole and ricobendazole have been used as anti-parasitic drugs for many years; their therapeutic action is based on the inhibition of microtubule formation. Therefore, the study of their properties as antitumor compounds and the design of an appropriate formulation for cancer therapy is an interesting issue to investigate. The selected compounds are poorly soluble in water, and consequently, they have low and erratic bioavailability. In order to improve their biopharmaceutics properties, several formulations employing cyclodextrin inclusion complexes were developed. To carefully evaluate the in vitro and in vivo antitumor activity of these drugs and their complexes, several studies were performed on a breast cancer cell line (4T1) and BALB/c mice. In vitro studies showed that albendazole presented improved antitumor activity compared with ricobendazole. Furthermore, albendazole:citrate-β-cyclodextrin complex decreased significantly 4T1 cell growth both in in vitro and in vivo experiments. Thus, new formulations for anti-parasitic drugs could help to reposition them for new therapeutic indications, offering safer and more effective treatments by using a well-known drug.

The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs

“…Supplementary Table 1 ( 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 ) summarizes the antitumorigenicity of benzimidazole anthelmintics on cancer cell lines. Benzimidazole anthelmintics inhibit the progression of cancer through a variety of mechanisms.…”

“…We summarized the antitumorigenicity of benzimidazole anthelmintics in animal tumor models ( Supplementary Table 2 ) ( 4 8 11 12 13 14 15 16 17 20 27 28 29 30 34 35 36 37 39 45 47 51 52 54 55 56 57 61 63 64 65 66 69 70 71 74 75 76 78 79 80 92 93 94 ). Benzimidazole anthelmintics have been shown to inhibit the tumor growth in animals, which have been well-tolerated without significant side effects during the experimental period.…”

An Approach to Enhance Dissolution Rate of Tamoxifen Citrate

“…Previous efforts to increase the solubility of TC have included the use of 0.5% w/v sodium lauryl sulfate alongside phosphate-buffered saline (PBS, pH 7.4) [7]. Furthermore, additional studies have demonstrated the use of hydroxyl propyl- β -cyclodextrin to improve the solubility of tamoxifen base, as well as TC, hydroxyl propyl- β -cyclodextrin [8, 9]. Here, we present a study on an optimization protocol aimed at improving the solubility and dissolution of TC.…”

Solid Polymeric Nanoparticles of Albendazole: Synthesis, Physico-Chemical Characterization and Biological Activity

“…Albendazole is a benzimidazole anthelminthic agent whose mechanism of action related to microtubule inhibition led to its reposition for extensive research as an antitumor agent [10]. The notable anti-proliferative activity of ABZ against several tumor cell lines was highlighted by numerous researches in the field [28]. ABZ has microtubule disrupting properties [29], inhibits angiogenesis by targeting the vascular endothelial growth factor (VEGF) expression [30] and is a potent inducer of apoptosis [4].…”