Preparation and evaluation of camptothecin analogues-loaded lyophilization using Kolliphor® HS 15 as carrier

FLQY2 is a camptothecin derivative modified by FL118 and proved to be good antitumor activity in vitro. However, its poor solubility leads to the low therapeutic efficacy in vivo. Here, the injectable FLQY2 lyophilized powder was prepared with Kolliphor® HS 15 (HS 15), which was called HS 15-FLQY2. The preparation process of HS 15-FLQY2 was optimized by orthogonal design and the lyophilization process was investigated by single factor experiment. Moreover, the formulation was characterized, the pharmacokinetics study and the antitumor activity were carried out in vivo. As the results, HS 15-FLQY2 (1:1500, w/w) containing 5% mannitol as cryoprotectant showed good appearance and 70% entrapment efficiency. HS 15-FLQY2 revealed low particle size (<16 nm), better homogeneity (PDI <0.2) and remained stable for 24 h in water. In addition, the data of the DSC, XRD and FTIR demonstrated that FLQY2 was distributed within micelles. In vivo, the bioavailability of HS 15-FLQY2 (i.p.) was improved significantly compared with oral CD-FLQY2 (a cyclodextrin inclusion complex of FLQY2). In addition, HS 15-FLQY2 demonstrated higher tumor inhibition effect than capecitabine, confirming the possibility of treatment cancer by the delivery of FLQY2.

Fei Wang, Xuyang Li, Xialin Hu, Wenya Zhuang, Jiewei Lai, Wenchao Wang, Xuanrong Sun, Hong Wang, Qingyong Li, Preparation and evaluation of camptothecin analogues-loaded lyophilization using Kolliphor® HS 15 as carrier, Journal of Drug Delivery Science and Technology, 2022, 103898, ISSN 1773-2247,
https://doi.org/10.1016/j.jddst.2022.103898.

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