TY - JOUR
T1 - A Deep Eutectic Solvent-Based Approach to Intravenous Formulation
AU - Kim, Jayoung
AU - Shi, Yujie
AU - Kwon, Christopher J.
AU - Gao, Yongsheng
AU - Mitragotri, Samir
N1 - Funding Information:
This work was supported by John A. Paulson School of Engineering at Harvard University. The authors acknowledge the Bauer Core Facility at Harvard University (flow cytometry) and the Wyss Institute (HPLC, TEM) for the support with instruments.
Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2021/9/22
Y1 - 2021/9/22
N2 - Clinically viable formulations of hydrophobic drugs, for example, chemotherapeutics, require strategies to promote sufficient drug solubilization. However, such strategies often involve the use of organic solvents that pose a significant risk in generating toxic, unstable products. Using verteporfin as a drug, a deep eutectic solvent (DES)-based approach to solvate drugs in a simple one-step process is reported. Lipoidal DES composed of choline and oleate is used to successfully solvate verteporfin, resulting in stable sub-100 nm nanocomplexes. The nanocomplexes successfully demonstrate efficient cellular uptake as well as retention, tumor spheroid penetration, and tumor accumulation in vivo. Systemic administration of the formulation significantly inhibits the primary tumor growth and its lung metastasis in the orthotopic 4T1 murine breast tumor model. Collectively, biocompatible DES shows great potential as a novel material for intravenous formulation of chemotherapeutics.
AB - Clinically viable formulations of hydrophobic drugs, for example, chemotherapeutics, require strategies to promote sufficient drug solubilization. However, such strategies often involve the use of organic solvents that pose a significant risk in generating toxic, unstable products. Using verteporfin as a drug, a deep eutectic solvent (DES)-based approach to solvate drugs in a simple one-step process is reported. Lipoidal DES composed of choline and oleate is used to successfully solvate verteporfin, resulting in stable sub-100 nm nanocomplexes. The nanocomplexes successfully demonstrate efficient cellular uptake as well as retention, tumor spheroid penetration, and tumor accumulation in vivo. Systemic administration of the formulation significantly inhibits the primary tumor growth and its lung metastasis in the orthotopic 4T1 murine breast tumor model. Collectively, biocompatible DES shows great potential as a novel material for intravenous formulation of chemotherapeutics.
KW - cellular uptake
KW - chemotherapy
KW - deep eutectic solvents
KW - nanocomplexes
KW - tumor penetration
UR - http://www.scopus.com/inward/record.url?scp=85111868065&partnerID=8YFLogxK
U2 - 10.1002/adhm.202100585
DO - 10.1002/adhm.202100585
M3 - Article
C2 - 34351085
AN - SCOPUS:85111868065
SN - 2192-2640
VL - 10
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 18
M1 - 2100585
ER -