Mohammadi Misagh, Karimi Mehrnaz, Raofie Farhad
Department of Analytical Chemistry and Pollutants, Shahid Beheshti University, Tehran, 1983969411, Iran.
Discov Nano. 2024 Sep 5;19(1):141. doi: 10.1186/s11671-024-04071-z.
A semi-synthetic camptothecin derivative known as irinotecan hydrochloride is frequently used to treat colorectal cancer, including colorectal adenocarcinoma and lung cancers involving small cells. Irinotecan has a very short half-life; therefore, continuous infusions are required to keep the drug's blood levels at therapeutic levels, which could produce cumulative toxicities. Effective delivery techniques, including liposomes, have been developed to address these shortcomings. In this study, a continuous supercritical fluid approach dubbed Expansion Supercritical Fluid into an aqueous solution, in which the pressure decreases rapidly but remains over the critical pressure, is proposed to manufacture polyethylene glycolylated (PEGylated) liposomes carrying irinotecan hydrochloride. To accomplish this, PEGylated liposomes were created using a Box-Behnken design, and the operating parameters (flow rate, temperature, and pressure drop) were optimized. Encapsulation efficiency, mean size, and prepared liposome count were 94.6%, 55 nm, and 758 under ideal circumstances. Additionally, the stability of the PEGylated liposome was investigated during 8 weeks, and also PEGylated liposome-loaded irinotecan release profile was compared to conventional liposomes and free irinotecan, and a constant drug release was seen after the first burst release from liposomes.
一种名为盐酸伊立替康的半合成喜树碱衍生物常用于治疗结直肠癌，包括结直肠腺癌和小细胞肺癌。伊立替康的半衰期非常短；因此，需要持续输注以将药物的血药浓度维持在治疗水平，这可能会产生累积毒性。为了解决这些缺点，已经开发了包括脂质体在内的有效递送技术。在本研究中，提出了一种名为“超临界流体膨胀进入水溶液”的连续超临界流体方法，其中压力迅速降低但仍高于临界压力，用于制备载有盐酸伊立替康的聚乙二醇化（PEG化）脂质体。为此，采用Box-Behnken设计制备了PEG化脂质体，并对操作参数（流速、温度和压降）进行了优化。在理想情况下，包封率、平均粒径和制备的脂质体数量分别为94.6%、55 nm和758。此外，还研究了PEG化脂质体在8周内的稳定性，并将载有PEG化脂质体的伊立替康释放曲线与传统脂质体和游离伊立替康进行了比较，脂质体首次突释后可见药物持续释放。
