Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Marburg, Germany.
Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan.
Int J Nanomedicine. 2021 Feb 11;16:951-976. doi: 10.2147/IJN.S285950. eCollection 2021.
Lipoparticles are the core-shell type lipid-polymer hybrid systems comprising polymeric nanoparticle core enveloped by single or multiple pegylated lipid layers (shell), thereby melding the biomimetic properties of long-circulating vesicles as well as the mechanical advantages of the nanoparticles. The present study was aimed at the development of such an integrated system, combining the photodynamic and chemotherapeutic approaches for the treatment of multidrug-resistant cancers.
For this rationale, two different sized Pirarubicin (THP) loaded poly lactic-co-glycolic acid (PLGA) nanoparticles were prepared by emulsion solvent evaporation technique, whereas liposomes containing Temoporfin (mTHPC) were prepared by lipid film hydration method. Physicochemical and morphological characterizations were done using dynamic light scattering, laser doppler anemometry, atomic force microscopy, and transmission electron microscopy. The quantitative assessment of cell damage was determined using MTT and reactive oxygen species (ROS) assay. The biocompatibility of the nanoformulations was evaluated with serum stability testing, haemocompatibility as well as acute in vivo toxicity using female albino (BALB/c) mice.
The mean hydrodynamic diameter of the formulations was found between 108.80 ± 2.10 to 405.70 ± 10.00 nm with the zeta (ζ) potential ranging from -12.70 ± 1.20 to 5.90 ± 1.10 mV. Based on the physicochemical evaluations, the selected THP nanoparticles were coated with mTHPC liposomes to produce lipid-coated nanoparticles (LCNPs). A significant (p< 0.001) cytotoxicity synergism was evident in LCNPs when irradiated at 652 nm, using an LED device. No incidence of genotoxicity was observed as seen with the comet assay. The LCNPs decreased the generalized in vivo toxicity as compared to the free drugs and was evident from the serum biochemical profile, visceral body index, liver function tests as well as renal function tests. The histopathological examinations of the vital organs revealed no significant evidence of toxicity suggesting the safety and efficacy of our lipid-polymer hybrid system.
脂粒是核壳型脂质-聚合物杂化系统，由聚合物纳米颗粒核包裹一层或多层聚乙二醇化脂质层（壳）组成，从而融合了长循环囊泡的仿生特性和纳米颗粒的机械优势。本研究旨在开发一种综合系统，将光动力和化学治疗方法结合用于治疗多药耐药性癌症。
基于这一原理，通过乳化溶剂蒸发技术制备了两种不同大小的吡柔比星（THP）负载的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒，而含有替莫泊芬（mTHPC）的脂质体则通过脂质膜水化法制备。采用动态光散射、激光多普勒动度计、原子力显微镜和透射电子显微镜对物理化学和形态特征进行了研究。使用 MTT 和活性氧（ROS）测定法对细胞损伤的定量评估。通过血清稳定性试验、血液相容性以及使用雌性白化（BALB/c）小鼠进行急性体内毒性试验来评估纳米制剂的生物相容性。
制剂的平均水动力直径为 108.80 ± 2.10 至 405.70 ± 10.00nm，ζ 电位为-12.70 ± 1.20 至 5.90 ± 1.10mV。基于物理化学评价，选择的 THP 纳米颗粒用 mTHPC 脂质体进行包衣，以产生脂质包覆的纳米颗粒（LCNPs）。当在 652nm 下用 LED 装置照射时，LCNPs 显示出显著的（p<0.001）细胞毒性协同作用。彗星试验未见遗传毒性。与游离药物相比，LCNPs 降低了全身性体内毒性，从血清生化谱、内脏体指数、肝功能试验和肾功能试验中可以看出。重要器官的组织病理学检查未显示出明显的毒性证据，表明该脂质-聚合物杂化系统具有安全性和有效性。
