盐酸小檗碱固体脂质纳米制剂减轻阿霉素诱导的 H9c2 大鼠心肌细胞炎症。
Solid Lipid Nanoformulation of Berberine Attenuates Doxorubicin Triggered Inflammation in H9c2 Rat Cardiomyocytes.
机构信息
Department of Pharmacology, AIIMS, New Delhi, India.
Department of Pathology, AIIMS, New Delhi, India.
出版信息
Comb Chem High Throughput Screen. 2022;25(10):1695-1706. doi: 10.2174/1386207325666220617113744.
AIM
The aim of this study was to evaluate the efficacy of solid lipid nanoparticles of berberine against doxorubicin-induced cardiotoxicity.
BACKGROUND
Berberine (Ber) is cardioprotective, but its oral bioavailability is low, and its effect on chemotherapy-induced cardiotoxicity has not been studied.
OBJECTIVE
Solid lipid nanoparticles (SLNs) of berberine chloride were prepared, characterized and evaluated in vitro against doxorubicin-induced cardiomyocyte injury.
METHODS
Berberine-loaded SLNs (Ber-SLNs) were synthesized using the water-in-oil microemulsion technique with tripalmitin, Tween 80 and poloxamer 407. Ber-SLNs were evaluated for preventive effect against toxicity of doxorubicin in H9c2 cells. The culture was pre-treated (24 h) with Ber (10 μM) and Ber-SLNs (1 and 10 μM), and 1 μM of doxorubicin (Dox) was added for 3 h. The cell viability assay (MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) and LDH (Lactate dehydrogenase)), levels of Creatine kinase-MB (CK-MB), Nitrite, MDA (Malondialdehyde), ROS (Reactive oxygen species) generation, and apoptotic DNA (Deoxyribonucleic acid) content were assessed.
RESULTS
Ber-SLNs had a mean particle size of 13.12±1.188 nm, the zeta potential of -1.05 ± 0.08 mV, poly-dispersity index (PDI) of 0.317 ± 0.05 and entrapment efficiency of 50 ± 4.8%. Cell viability was 81 ± 0.17% for Ber-SLNs (10 μM) and 73.22 ± 0.83% for Ber (10 μM) treated cells in the MTT assay. Percentage cytotoxicity calculated from LDH release was 58.91 ± 0.54% after Dox, 40.3 ± 1.3% with Ber (10 μM) and 40.7 ± 1.3% with Ber-SLNs (1 μM) (p<0.001). Inflammation and oxidative stress markers were lower with Ber and Ber-SLNs. Attenuation of ROS generation and apoptosis of cardiomyocytes were noted on fluorescence microscopy.
CONCLUSION
Ber SLNs effectively prevented doxorubicin-induced inflammation and oxidative stress in rat cardiomyocytes. The results demonstrate that microemulsion is a simple and costeffective technique to prepare Ber-SLNs, and may be considered as a drug delivery vehicle for berberine.
目的
本研究旨在评估盐酸小檗碱固体脂质纳米粒（Ber-SLNs）对阿霉素诱导的心脏毒性的疗效。
背景
小檗碱（Ber）具有心脏保护作用，但口服生物利用度低，其对化疗诱导的心脏毒性的影响尚未得到研究。
目的
采用水包油微乳液技术，以三棕榈酸甘油酯、吐温 80 和泊洛沙姆 407 制备盐酸小檗碱固体脂质纳米粒（Ber-SLNs），并在体外评价其对阿霉素诱导的心肌细胞损伤的防治作用。
方法
Ber-SLNs 采用水包油微乳液技术制备，以三棕榈酸甘油酯、吐温 80 和泊洛沙姆 407 为载体。采用 MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）和 LDH（乳酸脱氢酶）测定法评价 Ber 和 Ber-SLNs（1 和 10 μM）对阿霉素（Dox）毒性的预防作用。将细胞预先处理（24 h），加入 1 μM 的 Dox 3 小时。评估细胞活力测定（MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）和 LDH（乳酸脱氢酶））、肌酸激酶同工酶-MB（CK-MB）水平、硝酸盐、丙二醛（MDA）、活性氧（ROS）生成和凋亡 DNA（脱氧核糖核酸）含量。
结果
Ber-SLNs 的平均粒径为 13.12±1.188 nm，zeta 电位为-1.05±0.08 mV，多分散指数（PDI）为 0.317±0.05，包封效率为 50±4.8%。MTT 测定法中，Ber-SLNs（10 μM）处理的细胞活力为 81±0.17%，Ber（10 μM）处理的细胞活力为 73.22±0.83%。LDH 释放计算的细胞毒性百分比为 Dox 后 58.91±0.54%，Ber（10 μM）为 40.3±1.3%，Ber-SLNs（1 μM）为 40.7±1.3%（p<0.001）。Ber 和 Ber-SLNs 降低了炎症和氧化应激标志物。荧光显微镜观察到 ROS 生成和心肌细胞凋亡减少。
结论
Ber-SLNs 可有效预防阿霉素诱导的大鼠心肌细胞炎症和氧化应激。结果表明，微乳液是一种简单且具有成本效益的制备 Ber-SLNs 的技术，可考虑作为小檗碱的药物输送载体。
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