TY - JOUR
T1 - Influence of hydrolysis susceptibility and hydrophobicity of Sn-38 nano-prodrugs on their anticancer activity
AU - Koseki, Yoshitaka
AU - Ikuta, Yoshikazu
AU - Cong, Liman
AU - Takano-Kasuya, Mayumi
AU - Tada, Hiroshi
AU - Watanabe, Mika
AU - Gonda, Kohsuke
AU - Ishida, Takanori
AU - Ohuchi, Noriaki
AU - Tanita, Keita
AU - Taemaitree, Farsai
AU - Dao, Anh Thi Ngoc
AU - Onodera, Tsunenobu
AU - Oikawa, Hidetoshi
AU - Kasai, Hitoshi
PY - 2019
Y1 - 2019
N2 - In the field of drug delivery, controllability of drug release site and duration are among the most important factors to manipulate the drug efficacy and side effects. In this paper, a series of nano-prodrugs (NPs) composed of anticancer agent SN-38 and various substituent groups were synthesized and fabricated. By increasing the hydrophobicity of the prodrug molecule (calculated logP values exceeded ca. 7) through changing the substituent group, the hydrolysis susceptibility of SN-38 NPs in mouse serum was drastically decreased, thus prolonged the blood retention time of the NPs. In light of this knowledge and the dispersion stability in aqueous media, SN-38 NP modified with cholesterol (SN-38-chol NPs) was selected to be the optimal candidate among the screened NPs. The in vivo pharmacological effect of SN-38-chol NP was about 10 times higher than irinotecan, the clinically used solubilized prodrug analog of SN-38. In addition, SN-38-chol NP has low side effects in evaluating intestinal damage. These NPs possess great potential for clinical application and promise to be a next-generation of drug for cancer treatment.
AB - In the field of drug delivery, controllability of drug release site and duration are among the most important factors to manipulate the drug efficacy and side effects. In this paper, a series of nano-prodrugs (NPs) composed of anticancer agent SN-38 and various substituent groups were synthesized and fabricated. By increasing the hydrophobicity of the prodrug molecule (calculated logP values exceeded ca. 7) through changing the substituent group, the hydrolysis susceptibility of SN-38 NPs in mouse serum was drastically decreased, thus prolonged the blood retention time of the NPs. In light of this knowledge and the dispersion stability in aqueous media, SN-38 NP modified with cholesterol (SN-38-chol NPs) was selected to be the optimal candidate among the screened NPs. The in vivo pharmacological effect of SN-38-chol NP was about 10 times higher than irinotecan, the clinically used solubilized prodrug analog of SN-38. In addition, SN-38-chol NP has low side effects in evaluating intestinal damage. These NPs possess great potential for clinical application and promise to be a next-generation of drug for cancer treatment.
KW - Drug delivery
KW - Hydrolysis susceptibility
KW - Nano-prodrugs
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U2 - 10.1246/bcsj.20190088
DO - 10.1246/bcsj.20190088
M3 - Article
AN - SCOPUS:85072204385
VL - 92
SP - 1305
EP - 1313
JO - Bulletin of the Chemical Society of Japan
JF - Bulletin of the Chemical Society of Japan
SN - 0009-2673
IS - 8
ER -