In vitro anticancer evaluation of micelles containing N-(4-(2-((4-methoxybenzyl)amino)ethyl)phenyl)heptanamide, an analo
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Online ISSN 1976-3786 Print ISSN 0253-6269
RESEARCH ARTICLE
In vitro anticancer evaluation of micelles containing N‑(4‑(2‑((4‑methoxybenzyl)amino)ethyl)phenyl)heptanamide, an analogue of fingolimod Moon Sup Yoon1 · Yu Jin Lee1 · Chun‑Woong Park1 · Jin Tae Hong1 · Dong Jae Baek2 · Dae Hwan Shin1
Received: 26 July 2020 / Accepted: 21 October 2020 / Published online: 27 October 2020 © The Pharmaceutical Society of Korea 2020
Abstract Fingolimod has been evaluated for use as an anticancer agent. However, many steps are required to synthesize fingolimod because of its intricate structure. A fingolimod analogue, N-(4-(2-((4-methoxybenzyl)amino)ethyl) phenyl)heptanamide (MPH), also has anti-cancer effects and is easier to synthesize but is poorly soluble in water. To compensate for its poor water solubility, MPH-loaded polymeric micelles were prepared by thin film hydration method using various polymers and the physicochemical properties of the MPH-loaded micelles such as particle size, drug-loading (DL, %), and encapsulation efficiency (EE, %) were evaluated. A storage stability test was conducted to select the final formulation and the release profile of the MPH-loaded micelles was confirmed by in vitro release assay. MPHloaded mPEG-b-PLA micelles were selected for further testing based on their stability and physicochemical properties; they were stable for stable for 14 days at 4 °C and 25 °C and for 7 days at 37 °C. They showed anti-cancer efficacy against both A549 and U87 cancer cells. Encapsulation of MPH in polymeric micelles did not decrease the in vitro cytotoxicity of MPH. The findings of this study lay the groundwork for future formulations that enable the effective and stable delivery of poorly water-soluble agents. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12272-020-01276-5) contains supplementary material, which is available to authorized users. * Dae Hwan Shin [email protected] 1
College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1‑ro, Osong‑eup, Heungdeok‑gu, Cheongju 28160, Republic of Korea
2
College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, Republic of Korea
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Vol:.(1234567890)
Keywords MPH · Micelle · Physicochemical characterization · Drug release · Anti-cancer efficacy
Introduction Fingolimod (FTY720), which is synthesized based on the structure of myriocin, is the first FDA-approved oral treatment for multiple sclerosis; it has structural and biological properties similar to those of sphingosine, one of the cell signaling lipids that control cellular processes such as cell death and survival (Pitson 2011; Oaks et al. 2013). Fingolimod can induce apoptosis in peripheral lymphocytes; based on these observations, studies were conducted to determine whether fingolimod acted as an apoptosis-inducing anticancer agent (Tonelli et al. 2010). These studies confirmed that fingolimod has various cancer-inhibiting effects that are derived from its potent protein p
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