Taghizadeh Elnaz, Khamesipour Ali, Khoee Sepideh, Jaafari Mahmoud Reza, Hosseini Seyed Abdollah
Department of Chemistry, Alborz Campus, University of Tehran, Tehran, Iran.
Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2021 Fall;20(4):289-299. doi: 10.22037/ijpr.2021.115034.15162.
Amphotericin B (AMB) is a macrolide polyene antibiotic presenting potent anti-cutaneous activity. Nonetheless, its low water solubility, side effects, and toxicity have limited its therapeutic efficiency. The present study aimed to improve the solubility of AmB in oil-in-water using chitosan and determine its cytotoxicity on macrophages, as well as Leishmania major promastigote and amastigote. Olive oil, span 80, tween 80, AmB, and DMSO were employed as excipients, and nanoemulsions (NEs) were prepared by sonicator bath at 37 °C for 1 h at the highest power and stirred overnight with pH 5.5. Thereafter, chitosan was added to the NE and stirred overnight to obtain chitosan nanoemulsion (CNE). The CNE was optimized and investigated for different parameters, such as droplet size, zeta potential, morphology, drug content, drug release, and cytotoxicity. Droplet size and zeta potential for CNE with AmB were obtained at 13.33 ± 1.3 nm, 30.90 ± 1.9 mV, respectively. Encapsulation efficiency and drug loading of the final CNE were reported as 100% and 0.64%, respectively. The results of in-vitro cytotoxicity revealed that CNE did not cause any cytotoxicity in macrophages. The CNE not only reduced drug toxicity for the macrophage but also had a suitable inhibition effect on the parasite. The CNE with AmB exerted an inhibitory effect on promastigote/ amastigote phase. Furthermore, CNE with AmB represented a promising approach for leishmaniasis treatment. Therefore, the obtained outcomes of the IC proposed that the application of CNE can cause no toxicity and guarantees better quality drug release.
两性霉素B(AMB)是一种大环内酯类多烯抗生素,具有强大的抗皮肤活性。然而,其低水溶性、副作用和毒性限制了其治疗效果。本研究旨在利用壳聚糖提高AMB在水包油体系中的溶解度,并确定其对巨噬细胞、杜氏利什曼原虫前鞭毛体和无鞭毛体的细胞毒性。使用橄榄油、司盘80、吐温80、AMB和二甲基亚砜作为辅料,通过超声浴在37℃下以最大功率处理1小时制备纳米乳剂(NEs),并在pH 5.5条件下搅拌过夜。之后,将壳聚糖加入到纳米乳剂中并搅拌过夜,以获得壳聚糖纳米乳剂(CNE)。对CNE进行了优化,并研究了其不同参数,如粒径、zeta电位、形态、药物含量、药物释放和细胞毒性。含AMB的CNE的粒径和zeta电位分别为13.33±1.3纳米、30.90±1.9毫伏。最终CNE的包封率和载药量分别报告为100%和0.64%。体外细胞毒性结果显示,CNE对巨噬细胞没有引起任何细胞毒性。CNE不仅降低了对巨噬细胞的药物毒性,而且对寄生虫有适当的抑制作用。含AMB的CNE对前鞭毛体/无鞭毛体阶段具有抑制作用。此外,含AMB的CNE是治疗利什曼病的一种有前景的方法。因此,IC的所得结果表明,CNE的应用不会产生毒性,并保证了更好的药物释放质量。