Liposomal itraconazole formulation for the treatment of glioblastoma using inclusion complex with HP-β-CD
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Itraconazole, which has been widely used as an antifungal-agent, is revisited as an anticancer drug but its low solubility still remains a major hurdle.
Inclusion complex was used to enhance the solubility of itraconazole, followed by encapsulating into liposome for glioblastoma.
Itraconazole-inclusion complex was well formed at 1:1, 1:2 and 1:3 molar ratios of itraconazole: hydroxypropyl-β-cyclodextrin (HP-β-CD) as determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR) analyses. Itraconazole-HP-β-CD inclusion complex was then encapsulated in liposome and its size was 120.5 ± 53.1 nm in diameter with 50% encapsulation efficiency. Stem cell-like property, as determined by the population ratio of CD90+/CD133+, was decreased from 3.38 to 1.46% when the U87-MG-TL cells were treated with 100 µM itraconazole/HP-β-CD-loaded liposome. Anti-proliferative effect of itraconazole/HP-β-CD-loaded liposome on U87-MG-TL cells was slightly better than that of free itraconazole (IC50 of 17 µM vs. 26 µM). Moreover, anti-proliferative effect of Itraconazole/HP-β-CD-loaded liposome on U87-MG-TL cells was higher than that of free itraconazole when the cells were co-treated with temozolomide (IC50 of 1.58 mM vs. 2.35 mM).
Therefore, itraconazole/HP-β-CD-loaded liposomal formulation could serve as a promising strategy for targeting the glioblastoma multiforme.
KeywordsItraconazole Inclusion complex Liposome Glioblastoma multiforme Cyclodextrin
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2017R1D1A1B03030849) and the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MEST, No.2011-0030074).
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Conflict of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.