Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice.
Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice.
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临床前的全身毒性评估壳聚糖 - 固定脂质纳米颗粒封装的阿司匹林和姜黄素与BALB/C小鼠中的游离硫磷酸盐结合使用。
DOI：
10.2147/ijn.s106736
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发表时间：
2016
影响因子：
8
通讯作者：
Prabhu S
中科院分区：
文献类型：
--
作者：
Thakkar A;Chenreddy S;Thio A;Khamas W;Wang J;Prabhu S
我们之前的研究已经确定了封装在固体脂质纳米颗粒 (SLN) 中的阿司匹林和姜黄素 (CUR) 与游离萝卜硫素（ACS 组合）联合使用的化学预防方案可有效预防或延缓胰腺癌的发生和进展，胰腺癌被列为最致命的疾病之一，诊断后生存机会极低。尽管之前已经研究过单个药物和 SLN 的毒性，但当前文献中没有研究评估 ACS 联合方案的潜在毒性，特别是当封装在壳聚糖-SLN (c-SLN) 中时。因此，本研究的目的是调查 BALB/c 小鼠经口灌胃急性（3 天）、亚急性（28 天）和亚慢性（90 天）给药后 ACS c-SLN 联合化学预防方案的潜在毒性作用。给小鼠施用以下方案：盐水、空白c-SLN、低剂量ACS c-SLN (2+4.5+0.16 mg/kg)、中剂量ACS c-SLN (20+45+1.6 mg/kg)和高剂量ACS c-SLN (60+135+4.8 mg/kg)。根据动物存活、体重、血液学、血液化学和器官组织病理学评估潜在毒性。在 3 天、28 天和 90 天的研究期间，没有观察到动物死亡。 ACS c-SLN 治疗不会引起全血细胞计数和血液化学数据的改变。各种器官切片（胰腺、心脏、肝脏、肾脏和大脑）的组织病理学检查显示正常。根据这项研究的结果，在口服 ACS c-SLN 后的急性、亚急性和亚慢性研究中没有发现任何毒性迹象，表明口服给药方案在长期服用预防胰腺癌发作的测试水平上是安全的。
Our previous studies have established the efficacy of chemopreventive regimens of aspirin and curcumin (CUR) encapsulated within solid lipid nanoparticles (SLNs) in combination with free sulforaphane (ACS combination) to prevent or delay the initiation and progression of pancreatic cancer, classified as one of the deadliest diseases with very low chances of survival upon diagnosis. Although toxicity of individual drugs and SLN has been studied previously, there are no studies in current literature that evaluate the potential toxicity of a combined regimen of ACS, especially when encapsulated within chitosan-SLNs (c-SLNs). Hence, objective of the current study was to investigate the potential toxic effects of ACS c-SLN combined chemopreventive regimens following acute (3 days), subacute (28 days), and subchronic (90 days) administrations by oral gavage in BALB/c mice. Mice were administered the following regimens: saline, blank c-SLN, low-dose ACS c-SLN (2+4.5+0.16 mg/kg), medium-dose ACS c-SLN (20+45+1.6 mg/kg), and high-dose ACS c-SLN (60+135+4.8 mg/kg). The potential toxicity was evaluated based on animal survival, body weight, hematology, blood chemistry, and organ histopathology. During 3-day, 28-day, and 90-day study periods, no animal deaths were observed. Treatment with ACS c-SLNs did not cause alteration in complete blood counts and blood chemistry data. Histopathological examination of various organ sections (pancreas, heart, liver, kidney, and brain) appeared normal. Based on the results of this study, no signs of toxicity in acute, subacute, and subchronic studies following oral administration of ACS c-SLNs were found indicating that the oral dosing regimens were safe at the levels tested for long-term administration to prevent the onset of pancreatic cancer.