Optimization of nimesulide-loaded solid lipid nanoparticles (SLN) by factorial design, release profile and cytotoxicity in human Colon adenocarcinoma cell line
Optimization of nimesulide-loaded solid lipid nanoparticles (SLN) by factorial design, release profile and cytotoxicity in human Colon adenocarcinoma cell line
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DOI：
10.1080/10837450.2018.1549075
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发表时间：
2019-05-28
影响因子：
3.4
通讯作者：
Souto, Eliana B.
中科院分区：
文献类型：
--
作者：
Campos, Joana R.;Fernandes, Ana R.;Souto, Eliana B.
本工作的目的是通过2（2）析因设计开发一种用于装载尼美舒利（NiM）的无毒、长期稳定的固体脂质纳米粒（SLN）制剂。优化的处方由10wt%的山嵛酸甘油酯和2.5wt%的泊洛沙姆188组成。在生产后，NiM-SLN的Z平均值立即为166.1 +/-0.114 nm，多分散指数（PI）为0.171 +/-0051，ζ电位接近中性（-3.10 +/-0.166 mV）。对于在25 ℃下储存15天的NiM-SLN，记录到Z-Ave的轻微增加，而在4 ℃下，颗粒保持尺寸在类似范围内。使用TurbiscanLab（R）监测长期稳定性，显示纳米颗粒的高稳定性，背散射曲线的变化低于10%。NiM-SLN的释药模式为持续释放模式，约为100 mg/kg。30%的药物释放长达24 h。空SLN和NiM-SLN在将Caco-2细胞暴露于最高浓度（100 μ g/mL）长达48小时后是无毒的（细胞活力高于80%）。使用不同的冷冻保护剂冻干NiM-SLN，产生具有5%海藻糖的463.1 +/- 36.63 nm（PI 0.491 +/- 0.027）的颗粒。通过DSC证实了NiM-SLN的固体特征，NiM-SLN的重结晶指数为83%，冻干SLN的重结晶指数为74%。
The aim of this work is development of a nontoxic, long-term stable solid lipid nanoparticles (SLN) formulation for the loading of Nimesulide (NiM) by a 2(2) factorial design. The optimized formulation was composed of 10 wt% of glyceryl behenate and 2.5 wt% of poloxamer 188. Immediately after production, Z-Ave of NiM-SLN was 166.1 +/- 0.114 nm, with a polydispersity index (PI) of 0.171 +/- 0051 and zeta potential nearly neutral (-3.10 +/- 0.166 mV). A slight increase of Z-Ave was recorded for NiM-SLN stored at 25 degrees C for a period of 15 days, whereas at 4 degrees C particles kept size within similar range. Long-term stability was monitored using TurbiscanLab (R), showing a high stability of the nanoparticles with variations in the backscattering profiles below 10%. The release profile of NiM-SLN followed a sustained pattern with ca. 30% of drug released up to 24 h. Empty-SLN and NiM-SLN were nontoxic after exposing Caco-2 cells to the highest concentration (100 mu g/mL) up to 48 hours (cell viability higher than 80%). NiM-SLN were lyophilized using different cryoprotectants, producing particles of 463.1 +/- 36.63 nm (PI 0.491 +/- 0.027) with 5% trehalose. Solid character of NiM-SLN was confirmed by DSC, recording a recrystallization index of 83% for NiM-SLN and of 74% for lyophilized SLN.