PMID- 25687307
OWN - NLM
STAT- MEDLINE
DCOM- 20160309
LR  - 20181202
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 203
DP  - 2015 Apr 10
TI  - Determination of polymeric micelles' structural characteristics, and effect of 
      the characteristics on pharmacokinetic behaviors.
PG  - 77-84
LID - S0168-3659(15)00117-0 [pii]
LID - 10.1016/j.jconrel.2015.02.017 [doi]
AB  - We evaluated structural factors characterizing PEG-b-P(Asp-Bzl) micelles 
      including core size, aggregation number (Nagg), and core surface PEG density by 
      means of small-angle X-ray scattering (SAXS), field flow fractionation with 
      multi-angle light scattering (FFF-MALS) analysis, and DLS. Furthermore, we 
      evaluated the stability of PEG-b-P(Asp-Bzl) micelles by means of GPC. This paper 
      reports the correlation between the evaluated micelles' structural factors and 
      the micelles' behaviors including the micelles' in vivo pharmacokinetic 
      behaviors. One micelle PEG(12)-b-P(Asp-Bzl) (PEG=12,000) exhibited a high core 
      surface density (~0.99 chain/nm(2)). In these circumstances, PEG(12)-b-P(Asp-Bzl) 
      micelles exhibited a highly stretched PEG brush form. However, the evaluated core 
      surface PEG densities could not fully explain the micelles' in vivo 
      pharmacokinetic behaviors. In contrast, GPC will become a strong tool for 
      predicting PEG(12)-b-P(Asp-Bzl) micelles' in vivo behaviors, as well as the 
      micelles' in vitro behaviors. The stability results correlated strongly with the 
      area-under-the-curve (AUC) values of PEG-b-P(Asp-Bzl) micelles' in vivo 
      pharmacokinetics. Finally, we evaluated PEG(12)-b-P(Asp-Bzl) micelles' most 
      effective structural factor for determining the micelles' behaviors, and the 
      micelles' outermost shell surface's PEG density (DOS, PEG) correlated with the 
      micelles' behaviors. We revealed that the evaluated DOS, PEG is the most 
      important factor for understanding PEG(12)-b-P(Asp-Bzl) micelles' behaviors.
CI  - Copyright (c) 2015. Published by Elsevier B.V.
FAU - Shiraishi, Kouichi
AU  - Shiraishi K
AD  - Medical Engineering Laboratory, Research Center for Medical Sciences, The Jikei 
      University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, 
      Japan.
FAU - Sanada, Yusuke
AU  - Sanada Y
AD  - Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1 
      Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
FAU - Mochizuki, Shinichi
AU  - Mochizuki S
AD  - Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1 
      Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
FAU - Kawano, Kumi
AU  - Kawano K
AD  - Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, 
      Tokyo 142-8501, Japan.
FAU - Maitani, Yoshie
AU  - Maitani Y
AD  - Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1 
      Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
FAU - Sakurai, Kazuo
AU  - Sakurai K
AD  - Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1 
      Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan. Electronic address: 
      sakurai@kitakyu-u.ac.jp.
FAU - Yokoyama, Masayuki
AU  - Yokoyama M
AD  - Medical Engineering Laboratory, Research Center for Medical Sciences, The Jikei 
      University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, 
      Japan. Electronic address: masajun2093ryo@jikei.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150214
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Drug Carriers)
RN  - 0 (Micelles)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 7D96IR0PPM (pegaspargase)
RN  - EC 3.5.1.1 (Asparaginase)
SB  - IM
MH  - Animals
MH  - Asparaginase
MH  - Aspartic Acid/chemistry/pharmacokinetics
MH  - Cells, Cultured
MH  - Drug Carriers/*chemistry/*pharmacokinetics
MH  - Esterification
MH  - Macrophages/*metabolism
MH  - Mice, Inbred C57BL
MH  - *Micelles
MH  - Polyethylene Glycols/*chemistry/*pharmacokinetics
MH  - Scattering, Small Angle
MH  - X-Ray Diffraction
OTO - NOTNLM
OT  - Macrophage uptake
OT  - Outermost shell surface PEG density
OT  - Polymeric micelle
OT  - Small-angle X-ray scattering
OT  - Structural characteristics
EDAT- 2015/02/18 06:00
MHDA- 2016/03/10 06:00
CRDT- 2015/02/18 06:00
PHST- 2014/09/01 00:00 [received]
PHST- 2015/02/06 00:00 [revised]
PHST- 2015/02/12 00:00 [accepted]
PHST- 2015/02/18 06:00 [entrez]
PHST- 2015/02/18 06:00 [pubmed]
PHST- 2016/03/10 06:00 [medline]
AID - S0168-3659(15)00117-0 [pii]
AID - 10.1016/j.jconrel.2015.02.017 [doi]
PST - ppublish
SO  - J Control Release. 2015 Apr 10;203:77-84. doi: 10.1016/j.jconrel.2015.02.017. 
      Epub 2015 Feb 14.