Younis Mona K, Khalil Islam A, Younis Nancy S, Fakhr Eldeen Rasha R, Abdelnaby Rana M, Aldeeb Reem A, Taha Amal A, Hassan Doaa H
Department of Pharmaceutics, College of Pharmaceutical Science and Drug Manufacturing, Misr University for Science and Technology, 6th of October City 12566, Egypt.
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Biomedicines. 2023 Sep 14;11(9):2531. doi: 10.3390/biomedicines11092531.
Aceclofenac (ACF) is a widely used non-steroidal anti-inflammatory drug (NSAID) known for its effectiveness in treating pain and inflammation. Recent studies have demonstrated that ACF possesses antiproliferative properties, inhibiting the growth of cancer cells in various cancer cell lines. Citronellol, a monoterpenoid alcohol found in essential oils, exhibits antioxidant properties and activities such as inhibiting cell growth and acetylcholinesterase inhibition. In this study, the objective was to formulate and evaluate an aceclofenac/citronellol oil nanoemulsion for its antiproliferative effects on melanoma. The optimal concentrations of citronellol oil, Tween 80, and Transcutol HP were determined using a pseudoternary phase diagram. The formulated nanoemulsions were characterized for droplet size, zeta potential, thermophysical stability, and in vitro release. The selected formula (F1) consisted of citronellol oil (1 gm%), Tween 80 (4 gm%), and Transcutol HP (1 gm%). F1 exhibited a spherical appearance with high drug content, small droplet size, and acceptable negative zeta potential. The amorphous state of the drug in the nanoemulsion was confirmed by Differential Scanning Calorimetry, while FTIR analysis indicated its homogenous solubility. The nanoemulsion showed significant antiproliferative activity, with a lower IC50 value compared to aceclofenac or citronellol alone. Flow cytometric analysis revealed cell cycle arrest and increased apoptosis induced by the nanoemulsion. In silico studies provided insights into the molecular mechanism underlying the observed antitumor activity. In conclusion, the developed aceclofenac/citronellol oil nanoemulsion exhibited potent cytotoxicity and pro-apoptotic effects, suggesting its potential as a repurposed antiproliferative agent for melanoma treatment. In a future plan, further animal model research for validation is suggested.
醋氯芬酸（ACF）是一种广泛使用的非甾体抗炎药（NSAID），以其治疗疼痛和炎症的有效性而闻名。最近的研究表明，ACF具有抗增殖特性，可抑制多种癌细胞系中癌细胞的生长。香茅醇是一种存在于香精油中的单萜醇，具有抗氧化特性以及抑制细胞生长和乙酰胆碱酯酶抑制等活性。在本研究中，目的是制备并评估醋氯芬酸/香茅醇油纳米乳剂对黑色素瘤的抗增殖作用。使用伪三元相图确定香茅醇油、吐温80和二乙二醇单乙基醚（Transcutol HP）的最佳浓度。对制备的纳米乳剂进行粒径、zeta电位、热物理稳定性和体外释放特性的表征。所选配方（F1）由香茅醇油（1克/百分比）、吐温80（4克/百分比）和二乙二醇单乙基醚（1克/百分比）组成。F1呈现球形外观，药物含量高，粒径小，zeta电位为可接受的负值。通过差示扫描量热法证实纳米乳剂中药物的无定形状态，而傅里叶变换红外光谱（FTIR）分析表明其具有均匀的溶解性。该纳米乳剂显示出显著的抗增殖活性，与单独使用醋氯芬酸或香茅醇相比，其半数抑制浓度（IC50）值更低。流式细胞术分析显示纳米乳剂诱导细胞周期停滞并增加细胞凋亡。计算机模拟研究提供了对观察到的抗肿瘤活性潜在分子机制的见解。总之，所开发的醋氯芬酸/香茅醇油纳米乳剂表现出强大的细胞毒性和促凋亡作用，表明其作为用于黑色素瘤治疗的重新利用的抗增殖剂的潜力。在未来计划中，建议进一步开展动物模型研究以进行验证。
