TY - JOUR
T1 - Enhanced anticancer activity of drug nanoparticles formulated with β-cyclodextrin
AU - Zhan, Honglei
AU - Jagtiani, Tina
AU - Liang, Jun F.
N1 - Publisher Copyright:
© 2017 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016/12/6
Y1 - 2016/12/6
N2 - Camptothecin (CPT) is a potent chemotherapeutic agent that shows a broad spectrum of anticancer activities. However, it is clinically inactive because of poor aqueous solubility, rapid aqueous hydrolysis, and unexpected side effects. Three strategies have extensively been adopted to improve its dissolution rate including reduction of drug particle size to a nanoscale, use of an amorphous state, and the formation of inclusion compounds. In our study, we combined these three strategies together by constructing CPT nanoparticles by creating an inclusion complex with β-cyclodextrin (BCD). This new CPT formulation showed a rod-like structure of nanoscaled size and with semiamorphous or amorphous CPT. These BCD-CPT nanoparticles showed improved dissolution rate, stability, dispersion, and cellular uptake. When tested on cancer cells, BCD-CPT nanoparticles showed a much higher anticancer activity (IC50=14-28 μmol/l) in comparison with free CPT (IC50>500 μmol/l) and CPT nanocrystals (IC50>200 μmol/l). In addition, BCD-CPT nanoparticles can be physically mixed with CPT nanocrystals, leading to CPT formulations with tailored drug-release profiles to achieve customized therapeutics and flexible treatments in clinics.
AB - Camptothecin (CPT) is a potent chemotherapeutic agent that shows a broad spectrum of anticancer activities. However, it is clinically inactive because of poor aqueous solubility, rapid aqueous hydrolysis, and unexpected side effects. Three strategies have extensively been adopted to improve its dissolution rate including reduction of drug particle size to a nanoscale, use of an amorphous state, and the formation of inclusion compounds. In our study, we combined these three strategies together by constructing CPT nanoparticles by creating an inclusion complex with β-cyclodextrin (BCD). This new CPT formulation showed a rod-like structure of nanoscaled size and with semiamorphous or amorphous CPT. These BCD-CPT nanoparticles showed improved dissolution rate, stability, dispersion, and cellular uptake. When tested on cancer cells, BCD-CPT nanoparticles showed a much higher anticancer activity (IC50=14-28 μmol/l) in comparison with free CPT (IC50>500 μmol/l) and CPT nanocrystals (IC50>200 μmol/l). In addition, BCD-CPT nanoparticles can be physically mixed with CPT nanocrystals, leading to CPT formulations with tailored drug-release profiles to achieve customized therapeutics and flexible treatments in clinics.
KW - amorphous drug nanoparticles
KW - camptothecin
KW - drug delivery
KW - enhanced dissolution rate
KW - host-guest inclusion
KW - β-cyclodextrin
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U2 - 10.1097/CAD.0000000000000458
DO - 10.1097/CAD.0000000000000458
M3 - Article
C2 - 27926611
AN - SCOPUS:85002339069
SN - 0959-4973
VL - 28
SP - 271
EP - 280
JO - Anti-Cancer Drugs
JF - Anti-Cancer Drugs
IS - 3
ER -