Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India; Faculty of Pharmacy, Lincoln University College, Petaling Jaya, Selangor, Kuala Lumpur, 47301, Malaysia.
Regul Toxicol Pharmacol. 2017 Dec;91:179-189. doi: 10.1016/j.yrtph.2017.10.023. Epub 2017 Nov 6.
Oral paclitaxel (PTXL) formulations freed from cremophor EL (CrEL) is always in utmost demand by the cancerous patients due to toxicities associated with the currently marketed formulation. In our previous investigation [Int. J. Pharm. 2014; 460:131], we have developed an oral oil based nanocarrier for the lipophilic drug, PTXL to target bioavailability issue and patient compliance. Here, we report in vivo antitumor activity and 28-day sub-chronic toxicity of the developed PTXL nanoemulsion. It was observed that the apoptotic potential of oral PTXL nanoemulsion significantly inhibited the growth of solid tumor (59.2 ± 7.17%; p < 0.001) without causing any explicit toxicity. The 6.5 mg/kg and 3 mg/kg oral PTXL nanoemulsion dose did not cause any notable alteration in haematological, biochemical/structural characteristics during 28-day sub-chronic toxicity studies in the experimental mice. Whereas, the toxicity of 12.8 mg/kg body weight dose showed decrease in RBC, haemoglobin and neutrophil counts. In contrast, marketed PTXL (Taxol) was found to be comparatively more toxic to the experimental animals. Taxol treatment resulted glomerulonephritis in histopathological examination, which could be correlated with increased level of creatinine and associated nephrotoxicity. This investigations conclude that the developed oral nanoemulsion presents a viable therapeutics bio-system to step towards clinical application as well as substitute CrEL based PTXL formulations.
由于与目前市售制剂相关的毒性，癌症患者一直非常需要不含 Cremophor EL（CrEL）的口服紫杉醇（PTXL）制剂。在我们之前的研究中[Int. J. Pharm. 2014; 460:131]，我们已经开发了一种用于脂溶性药物 PTXL 的口服油基纳米载体，以解决生物利用度问题和患者顺应性。在这里，我们报告了所开发的 PTXL 纳米乳剂的体内抗肿瘤活性和 28 天亚慢性毒性。结果表明，口服 PTXL 纳米乳剂的凋亡潜力显著抑制了实体瘤的生长（59.2 ± 7.17%；p < 0.001），而没有引起任何明显的毒性。在实验小鼠的 28 天亚慢性毒性研究中，6.5mg/kg 和 3mg/kg 的口服 PTXL 纳米乳剂剂量未引起血液学、生化/结构特征的任何明显改变。然而，12.8mg/kg 体重剂量的毒性表现为红细胞、血红蛋白和中性粒细胞计数减少。相比之下，市售的 PTXL（紫杉醇）被发现对实验动物的毒性更大。紫杉醇治疗导致组织病理学检查中的肾小球肾炎，这可能与肌酐水平升高和相关的肾毒性有关。这些研究得出的结论是，所开发的口服纳米乳剂为临床应用提供了一种可行的治疗生物系统，也可以替代基于 CrEL 的 PTXL 制剂。
