■目前,肝细胞癌(HCC)的常规治疗对肿瘤组织的选择性不足,导致多药耐药和药物毒性。尽管索拉非尼(SOR)是批准用于HCC临床治疗的标准一线全身疗法,其不良的水溶性和快速清除导致低的吸收效率并严重限制其用于局部治疗。
■这里,我们介绍了生物可降解聚合物聚(D,D,通过乳液-溶剂蒸发过程负载有SOR(PS)的L-丙交酯-共-乙交酯)(PLGA)颗粒。对颗粒进行仔细表征,专注于颗粒大小,表面电荷,形态学,载药量,封装效率,体外稳定性,药物释放行为并在HepG2细胞上进行了测试。此外,PLGA颗粒已经耦合在集成在微流体装置中的侧发射光纤(seOF)上,用于光触发的局部释放。
■PS的尺寸为248nm,可调的表面电荷和均匀的球形没有聚集。PS显示89.7%的包封效率和负载SOR的PLGA制剂之间的最高药物负载(8.9%)。用含有7.5µMSOR的PS处理HepG2细胞,它们的活力被抑制到40%,孵育48、129和168小时后的30%和17%,分别。
■高PS稳定性,它们的持续释放曲线和快速的细胞摄取证实了对HepG2的增强的细胞毒性作用。随着开发生物医学工具以控制药物的时空释放的前景,我们成功地证明了seOF光触发载体局部释放的潜力。我们的原型系统为集成微流体的新设备铺平了道路,光纤,和先进的载体能够提供微创局部癌症治疗。
UNASSIGNED: Currently, conventional treatments of hepatocellular carcinoma (HCC) are not selective enough for tumor tissue and lead to multidrug resistance and drug toxicity. Although sorafenib (SOR) is the standard first-line systemic therapy approved for the clinical treatment of HCC, its poor aqueous solubility and rapid clearance result in low absorption efficiency and severely limit its use for local treatment.
UNASSIGNED: Herein, we present the synthesis of biodegradable polymeric Poly (D, L-Lactide-co-glycolide) (PLGA) particles loaded with SOR (PS) by emulsion-solvent evaporation process. The particles are carefully characterized focusing on particle size, surface charge, morphology, drug loading content, encapsulation efficiency, in vitro stability, drug release behaviour and tested on HepG2 cells. Additionally, PLGA particles have been coupled on side emitting optical fibers (seOF) integrated in a microfluidic device for light-triggered local release.
UNASSIGNED: PS have a size of 248 nm, tunable surface charge and a uniform and spherical shape without aggregation. PS shows encapsulation efficiency of 89.7% and the highest drug loading (8.9%) between the SOR-loaded PLGA formulations. Treating HepG2 cells with PS containing SOR at 7.5 µM their viability is dampened to 40%, 30% and 17% after 48, 129 and 168 hours of incubation, respectively.
UNASSIGNED: The high PS stability, their sustained release profile and the rapid cellular uptake corroborate the enhanced cytotoxicity effect on HepG2. With the prospect of developing biomedical tools to control the spatial and temporal release of drugs, we successfully demonstrated the potentiality of seOF for light-triggered local release of the carriers. Our prototypical system paves the way to new devices integrating microfluidics, optical fibers, and advanced carriers capable to deliver minimally invasive locoregional cancer treatments.