TY - JOUR
T1 - Preparation and anticancer activity evaluation of an amorphous drug nanocomposite by simple heat treatment
AU - Zhan, Honglei
AU - Liang, Jun F.
N1 - Publisher Copyright:
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - The solubility of drug molecules is closely related to its bioactivity as it affects the dissolution rate and bioavailability, especially in the case of BCS IV drugs like camptothecin (CPT), a potential broad-spectrum anticancer agent. In this study, we construct a novel boric acid (BA)- coated CPT nanocomposite by means of a simple heattreatment approach, which combines nanoscale size range and amorphous solid state together to improve the overall dissolution rate of CPT. This new CPT formulation showed a rod-like structure with nanoscale size and amorphous solid nature. These BA-coated CPT nanocomposites exhibited a dramatically improved dissolution rate, water dispersion property, and long-term chemical and physical stability. More importantly, the specific reactivity of BA groups to diols in the cell glycocalyx facilitated a rapid crossmembrane translocation of the drug nanocomposite, leading to efficient intracellular drug delivery. When tested on A549 cells and SKBR3 cells, this formulation demonstrated a much higher anticancer activity in comparison with free CPT, naked amorphous CPT nanoparticles, and control CPT nanocrystals. This formulation has great potential for clinical application; it is easy to scale up and be applied on other hydrophobic drugs.
AB - The solubility of drug molecules is closely related to its bioactivity as it affects the dissolution rate and bioavailability, especially in the case of BCS IV drugs like camptothecin (CPT), a potential broad-spectrum anticancer agent. In this study, we construct a novel boric acid (BA)- coated CPT nanocomposite by means of a simple heattreatment approach, which combines nanoscale size range and amorphous solid state together to improve the overall dissolution rate of CPT. This new CPT formulation showed a rod-like structure with nanoscale size and amorphous solid nature. These BA-coated CPT nanocomposites exhibited a dramatically improved dissolution rate, water dispersion property, and long-term chemical and physical stability. More importantly, the specific reactivity of BA groups to diols in the cell glycocalyx facilitated a rapid crossmembrane translocation of the drug nanocomposite, leading to efficient intracellular drug delivery. When tested on A549 cells and SKBR3 cells, this formulation demonstrated a much higher anticancer activity in comparison with free CPT, naked amorphous CPT nanoparticles, and control CPT nanocrystals. This formulation has great potential for clinical application; it is easy to scale up and be applied on other hydrophobic drugs.
KW - Amorphous drug nanocomposite
KW - Boric-acid coating
KW - Camptothecin
KW - Drug delivery
KW - Enhanced dissolution rate
KW - Heat treatment
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U2 - 10.1097/CAD.0000000000000503
DO - 10.1097/CAD.0000000000000503
M3 - Article
C2 - 28368904
AN - SCOPUS:85016964958
SN - 0959-4973
VL - 28
SP - 623
EP - 633
JO - Anti-Cancer Drugs
JF - Anti-Cancer Drugs
IS - 6
ER -