Effective accumulation of poly(vinylpyrrolidone-co-vinyl laurate) into the spleen.
To optimize polymer-conjugated drugs as a polymeric drug delivery system, it is essential to design polymeric carriers with tissue-specific targeting capacity. Previously, we showed that polyvinylpyrrolidone (PVP) was the most suitable polymeric carrier for prolonging the blood-residency of drugs, and was one of the best parent polymers to design the polymeric carriers with targeting capacity. In this study, we synthesized some hydrophobic PVP derivatives, poly(vinylpyrrolidone-co-styrene) [poly(VP-co-S)] and poly(vinylpyrrolidone-co-vinyl laurate) [poly(VP-co-VL)], and assessed their biopharmaceutical properties after intravenous administration in mice. The elimination of hydrophobic PVP derivatives from blood was the same as PVP, and the plasma half-lives of poly(VP-co-S) were almost similar to that of poly(VP-co-VL). Poly(VP-co-VL) efficiently accumulated in the spleen, whereas poly(VP-co-S) effectively accumulated in the liver. The level of poly(VP-co-VL) in the spleen was about 20 times higher than PVP and poly(VP-co-S). These hydrophobic PVP derivatives did not show any cytotoxicity against endothelial cells in vitro. Thus, poly(VP-co-VL) may be a useful polymeric carrier for drug delivery to the spleen. This study will provide useful information to design optimal polymeric carriers with targeting capacity to the spleen and liver.
Yoshioka
Yasuo
Y
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tsutsumi
Yasuo
Y
Mukai
Yohei
Y
Shibata
Hiroko
H
Okamoto
Takayuki
T
Kaneda
Yoshihisa
Y
Tsunoda
Shin-ichi
S
Kamada
Haruhiko
H
Koizumi
Keiichi
K
Yamamoto
Yoko
Y
Mu
Yu
Y
Kodaira
Hiroshi
H
Sato-Kamada
Keiko
K
Nakagawa
Shinsaku
S
Mayumi
Tadanori
T
D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005453:Fluorescence; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008422:Materials Testing; D051379:Mice; D008968:Molecular Conformation; D011205:Povidone / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D013154:Spleen / Q000378:metabolism*; D014018:Tissue Distribution
D001672:Biocompatible Materials; D004337:Drug Carriers; D011205:Povidone