SN-38-cyclodextrin complexation and its influence on the solubility, stability, and in vitro anticancer activity against ovarian cancer. Academic Article uri icon


  • SN-38, an active metabolite of irinotecan, is up to 1,000-fold more potent than irinotecan. But the clinical use of SN-38 is limited by its extreme hydrophobicity and instability at physiological pH. To enhance solubility and stability, SN-38 was complexed with different cyclodextrins (CDs), namely, sodium sulfobutylether -cyclodextrin (SBECD), hydroxypropyl -cyclodextrin, randomly methylated -cyclodextrin, and methyl -cyclodextrin, and their influence on SN-38 solubility, stability, and in vitro cytotoxicity was studied against ovarian cancer cell lines (A2780 and 2008). Phase solubility studies were conducted to understand the pattern of SN-38 solubilization. SN-38-CD complexes were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction analysis (XRPD), and Fourier transform infrared (FTIR). Stability of SN-38-SBECD complex in pH 7.4 phosphate-buffered saline was evaluated and compared against free SN-38. Phase solubility studies revealed that SN-38 solubility increased linearly as a function of CD concentration and the linearity was characteristic of an AP-type system. Aqueous solubility of SN-38 was enhanced by about 30-1,400 times by CD complexation. DSC, XRPD, and FTIR studies confirmed the formation of inclusion complexes, and stability studies revealed that cyclodextrin complexation significantly increased the hydrolytic stability of SN-38 at physiological pH 7.4. Cytotoxicity of SN-38-SBECD complex was significantly higher than SN-38 and irinotecan in both A2780 and 2008 cell lines. Results suggest that SBECD encapsulated SN-38 deep into the cavity forming stable inclusion complex and as a result increased the solubility, stability, and cytotoxicity of SN-38. It may be concluded that preparation of inclusion complexes with SBECD is a suitable approach to overcome the solubility and stability problems of SN-38 for future clinical applications.

published proceedings

  • AAPS PharmSciTech

altmetric score

  • 1.5

author list (cited authors)

  • Vangara, K. K., Ali, H. I., Lu, D., Liu, J. L., Kolluru, S., & Palakurthi, S.

citation count

  • 29

complete list of authors

  • Vangara, Kiran Kumar||Ali, Hamed Ismail||Lu, Dai||Liu, Jingbo Louise||Kolluru, Srikanth||Palakurthi, Srinath

publication date

  • April 2014