BACKGROUND Rosuvastatin (RSV) is a poorly water-soluble drug that has an absolute oral bioavailability of only 20%. The aim of this work was to prepare a positively charged chitosan coated flexible lipid-based vesicles (chitosomes) and compare their characteristics to the corresponding negatively charged flexible liposomal nanoparticles (NPs) in order to develop new RSV nanocarrier systems. METHODS Three formulation factors affecting the development of chitosomes nano-formulation were optimized for their effects on the particles size, entrapment efficiency (EE) and zeta potential. The optimized flexible chitosomes and their corresponding liposomal NPs were characterized for morphology, in vitro release, flexibility and intestinal cell viability. The half maximum inhibitory concentrations (IC50) for both formulations were calculated. RESULTS The drug to lipid molar ratio, edge activator percent and the chitosan concentration were significantly affecting the characteristics of NPs. The optimized chitosomes nano-formulation exhibited larger size, higher EE and greater zeta potential value when compared to the corresponding liposomal NPs. Both formulations showed a spherical shape nanostructure with a marked outer shell for the chitosomes nano-formulation. Chitosomes illustrated an extended drug release profile when compared with the corresponding liposomal NPs and the prepared drug suspension. Flexibility of both vesicles was confirmed with superiority of liposomal NPs over chitosomes. RSV loaded chitosomes nano-formulation exhibited lower IC50 values and higher therapeutic window while liposomal NPs were compatible with the intestinal cells. CONCLUSIONS RSV loaded chitosomes nano-formulation could be considered as a promising nanocarrier system with a marked cytotoxic activity while, RSV loaded liposomal NPs are suitable nanocarrier to improve RSV activity in treatment of cardiovascular disorders.

中文翻译：

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罗苏伐他汀柔性脂质基纳米颗粒的开发：有望改善肠道细胞细胞毒性的纳米载体。

背景技术瑞舒伐他汀（RSV）是水溶性差的药物，其绝对口服生物利用度仅为20％。这项工作的目的是制备带正电荷的壳聚糖包被的基于柔性脂质的囊泡（壳聚糖），并将其特性与相应的带负电荷的柔性脂质体纳米颗粒（NP）进行比较，以开发新的RSV纳米载体系统。方法优化了影响壳聚糖纳米制剂发展的三个制剂因素，这些因素对颗粒大小，包封率（EE）和ζ电位具有影响。优化的柔性壳聚糖及其相应的脂质体NPs的形态，体外释放，柔韧性和肠细胞活力均经过表征。计算两种制剂的最大半数抑制浓度（IC50）。结果药物与脂质的摩尔比，边缘活化剂百分比和壳聚糖浓度均显着影响NPs的特性。与相应的脂质体NPs相比，优化的壳聚糖纳米制剂表现出更大的尺寸，更高的EE和更大的ζ电势值。两种制剂均显示出球形纳米结构，其壳壳纳米制剂具有明显的外壳。与相应的脂质体NP和制备的药物悬浮液相比，壳聚糖显示出延长的药物释放曲线。脂质体NPs比壳聚糖的优越性证实了两个囊泡的柔性。载有RSV的壳聚糖纳米制剂表现出较低的IC50值和较高的治疗窗口，而脂质体NP与肠细胞相容。