Department of Chemical & Biological Engineering, Gachon University, Sungnam 13120, Republic of Korea.
Department of Bionanotechnology, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Gyeonggi-Do 461-701, Republic of Korea.
Eur J Pharm Biopharm. 2019 Sep;142:518-530. doi: 10.1016/j.ejpb.2019.07.024. Epub 2019 Jul 28.
Despite substantial advancements in divergent drug delivery systems (DDS), there is still room for novel and innovative nanoparticle-mediated drug delivery methodologies such as core/shell liposomes to deliver drugs in a kinetically controlled manner into the active site without any side effects. Herein, ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl) bis (2-methoxy-4,1-phenylene) diacetate acetyl curcumin (AC)-loaded poly(lactic-co-glycolic acid) (PLGA) core/shell liposome nanoparticles (ACPCSLNPs) were prepared using an electron spray method under an applied electric field, which facilitated the uniform formation of nano-sized liposome nanoparticles (LNPs). Then, kinetically controlled and sustained drug release profiles were investigated using the as-prepared ACPCSLNPs. Moreover, the inner polymeric core could not only induce the generation of electrostatic interactions between the polymer and drug molecules but could also affect the prominent repulsions between the polar head groups of lipids and the nonpolar drug molecules. As a result, the sustained maximum release of the drug molecules (48.5%) into the system was observed over a long period (4 days). Furthermore, cell cytotoxicity studies were conducted in a human cervical cancer cell line (HeLa) and a healthy human dermal fibroblast cell line (HDFa) by employing all AC loaded LNPs along with free drugs. Multicolor cell imaging was also observed in HeLa cells using ACPCSLNPs. Notably, more curcumin was released from the ACPCSLNPs than AC due to the presence of polar group attractions and polar-polar interactions between the lipid head groups and curcumin since curcumin is more soluble than AC in aqueous medium. In addition, the predictions of the release kinetic patterns were also investigated thoroughly using the exponential-based Korsmeyer-Peppas (K-P) and Higuchi models for drug-loaded LNPs and PLGA NPs, respectively.
尽管在药物传递系统(DDS)方面取得了重大进展,但仍有空间采用新型创新的纳米颗粒介导的药物传递方法,例如核/壳脂质体,以无任何副作用的方式将药物以动力学控制的方式递送到活性部位。在此,采用电子喷雾法在施加电场的情况下制备了(1E,6E)-3,5-二氧代庚-1,6-二烯-1,7-二基)双(2-甲氧基-4,1-亚苯基)二乙酸乙酰姜黄素(AC)负载的聚(乳酸-共-羟基乙酸)(PLGA)核/壳脂质体纳米粒(ACPCSLNPs),这有利于纳米尺寸脂质体纳米粒(LNPs)的均匀形成。然后,使用所制备的 ACPCSLNPs 研究了动力学控制和持续的药物释放曲线。此外,内部聚合物核不仅可以诱导聚合物和药物分子之间产生静电相互作用,还可以影响脂质的极性头基与非极性药物分子之间的明显排斥力。结果,观察到药物分子(48.5%)在系统中以较长时间(4 天)持续最大释放。此外,通过使用所有负载 AC 的 LNPs 以及游离药物,在人宫颈癌细胞系(HeLa)和健康人真皮成纤维细胞系(HDFa)中进行了细胞细胞毒性研究。还使用 ACPCSLNPs 在 HeLa 细胞中观察到多色细胞成像。值得注意的是,由于脂质头部基团与姜黄素之间存在极性基团吸引力和极性-极性相互作用,并且由于姜黄素在水性介质中比 AC 更具溶解性,因此从 ACPCSLNPs 中释放出的姜黄素比 AC 更多。此外,还分别使用基于指数的 Korsmeyer-Peppas(K-P)和 Higuchi 模型对载药 LNPs 和 PLGA NPs 的释放动力学模式进行了深入预测。