TY - JOUR
T1 - Solubilization of poorly water-soluble compounds using amphiphilic phospholipid polymers with different molecular architectures
AU - Mu, Mingwei
AU - Konno, Tomohiro
AU - Inoue, Yuuki
AU - Ishihara, Kazuhiko
N1 - Funding Information:
The authors thank Dr. Kyoko Fukazawa, the University of Tokyo for her valuable research comments. Part of this research was supported by a Grant-in-Aid for Scientific Research on Innovative Areas “Nanomedicine Molecular Science” (No. 2306) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and in part by a Grant-in-Aid for Scientific Research (B) (17H02097) from the Japan Society for the Promotion of Science (JSPS).
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - To achieve stable and effective solubilization of poorly water-soluble bioactive compounds, water-soluble and amphiphilic polymers composed of hydrophilic 2-methacryloyloxyethyl phosphorylcholine (MPC) units and hydrophobic n-butyl methacrylate (BMA) units were prepared. MPC polymers having different molecular architectures, such as random-type monomer unit sequences and block-type sequences, formed polymer aggregates when they were dissolved in aqueous media. The structure of the random-type polymer aggregate was loose and flexible. On the other hand, the block-type polymer formed polymeric micelles, which were composed of very stable hydrophobic poly(BMA) cores and hydrophilic poly(MPC) shells. The solubilization of a poorly water-soluble bioactive compound, paclitaxel (PTX), in the polymer aggregates was observed, however, solubilizing efficiency and stability were strongly depended on the polymer architecture; in other words, PTX stayed in the poly(BMA) core of the polymer micelle formed by the block-type polymer even when plasma protein was present in the aqueous medium. On the other hand, when the random-type polymer was used, PTX was transferred from the polymer aggregate to the protein. We conclude that water-soluble and amphiphilic MPC polymers are good candidates as solubilizers for poorly water-soluble bioactive compounds.
AB - To achieve stable and effective solubilization of poorly water-soluble bioactive compounds, water-soluble and amphiphilic polymers composed of hydrophilic 2-methacryloyloxyethyl phosphorylcholine (MPC) units and hydrophobic n-butyl methacrylate (BMA) units were prepared. MPC polymers having different molecular architectures, such as random-type monomer unit sequences and block-type sequences, formed polymer aggregates when they were dissolved in aqueous media. The structure of the random-type polymer aggregate was loose and flexible. On the other hand, the block-type polymer formed polymeric micelles, which were composed of very stable hydrophobic poly(BMA) cores and hydrophilic poly(MPC) shells. The solubilization of a poorly water-soluble bioactive compound, paclitaxel (PTX), in the polymer aggregates was observed, however, solubilizing efficiency and stability were strongly depended on the polymer architecture; in other words, PTX stayed in the poly(BMA) core of the polymer micelle formed by the block-type polymer even when plasma protein was present in the aqueous medium. On the other hand, when the random-type polymer was used, PTX was transferred from the polymer aggregate to the protein. We conclude that water-soluble and amphiphilic MPC polymers are good candidates as solubilizers for poorly water-soluble bioactive compounds.
KW - MPC polymer
KW - Paclitaxel
KW - Polymer aggregate
KW - Polymeric micelle
KW - Solubilization
KW - Water-soluble amphiphilic polymer
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U2 - 10.1016/j.colsurfb.2017.06.040
DO - 10.1016/j.colsurfb.2017.06.040
M3 - Article
C2 - 28700969
AN - SCOPUS:85022019887
SN - 0927-7765
VL - 158
SP - 249
EP - 256
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
ER -