PMID- 29097141
OWN - NLM
STAT- MEDLINE
DCOM- 20180830
LR  - 20181202
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 535
IP  - 1-2
DP  - 2018 Jan 15
TI  - Self-assembled nanocomplex of PEGylated protamine and heparin-suramin conjugate 
      for accumulation at the tumor site.
PG  - 38-46
LID - S0378-5173(17)31035-9 [pii]
LID - 10.1016/j.ijpharm.2017.10.055 [doi]
AB  - Heparin-like sulfated polysaccharides are potential drug candidates owing to 
      their ability to interact with angiogenic factors and inhibit angiogenesis, tumor 
      growth, and metastasis. This study aimed to improve the delivery of heparin-like 
      anticancer polysaccharides for accumulation at the tumor site. We designed a 
      nanocarrier system using protamine attached to polyethylene glycol (PEG) and 
      evaluated the stability, tumor targeting, and tumor growth inhibition of the 
      nanocarrier loaded with heparin derivatives. When mixed with various polyanionic 
      heparin derivatives, the polycationic PEG-protamine formed stable self-assembled 
      nanocomplexes via ionic interactions, with flexible PEG chains located on the 
      outside. Among the complexes, a nanocomplex loaded with a low-molecular-weight 
      heparin-suramin conjugate (LHsura) had the most suitable average size (101.9nm) 
      for the enhanced permeability and retention effect and allowed accumulation of 
      LHsura at the tumor site for up to 48h. In a tumor-bearing mouse model, the 
      PEG-protamine and LHsura nanocomplex (10mg/kg/3days, intravenously), which could 
      be extravasated through the tumor vasculature, significantly inhibited tumor 
      growth, more than LHsura alone did. Overall, the self-assembled nanocomplexation 
      of PEG-protamine and LHsura helped control the release and extravasation of 
      LHsura, which resulted in an antitumor effect on the target tumor cells.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Park, Jooho
AU  - Park J
AD  - Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul 
      National University, Seoul, 151-742, Republic of Korea; Center for Theragnosis, 
      Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 
      136-791, Republic of Korea.
FAU - Hwang, Seung Rim
AU  - Hwang SR
AD  - College of Pharmacy, Chosun University, Gwangju, 501-759, Republic of Korea; 
      Department of Biomedical Sciences, Graduate School, Chosun University, Gwangju, 
      501-759, Republic of Korea.
FAU - Choi, Jeong Uk
AU  - Choi JU
AD  - Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul 
      National University, Seoul, 151-742, Republic of Korea.
FAU - Alam, Farzana
AU  - Alam F
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University 
      Health Sciences Center, Amarillo, TX, 79106, USA.
FAU - Byun, Youngro
AU  - Byun Y
AD  - Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul 
      National University, Seoul, 151-742, Republic of Korea; Department of Molecular 
      Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science 
      and Technology, College of Pharmacy, Seoul National University, 1 Gwanak-ro, 
      Gwanak-gu, Seoul, 151-742, Republic of Korea. Electronic address: 
      yrbyun@snu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20171031
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Drug Carriers)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Nanoconjugates)
RN  - 0 (Protamines)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 6032D45BEM (Suramin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage
MH  - Cell Line, Tumor
MH  - Drug Carriers/chemical synthesis/*chemistry/pharmacokinetics
MH  - Heparin, Low-Molecular-Weight/*chemistry/pharmacokinetics
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Molecular Docking Simulation
MH  - Nanoconjugates/*chemistry
MH  - Neoplasms, Experimental/*metabolism
MH  - Particle Size
MH  - Polyethylene Glycols/chemistry
MH  - Protamines/*chemistry/pharmacokinetics
MH  - Suramin/*chemistry/pharmacokinetics
MH  - Surface Properties
MH  - Tissue Distribution
OTO - NOTNLM
OT  - Heparin
OT  - Polyethylene glycol
OT  - Protamine
OT  - Self-assembled nanocomplex
OT  - Suramin
OT  - Tumor targeting
EDAT- 2017/11/04 06:00
MHDA- 2018/08/31 06:00
CRDT- 2017/11/04 06:00
PHST- 2017/06/28 00:00 [received]
PHST- 2017/10/24 00:00 [revised]
PHST- 2017/10/29 00:00 [accepted]
PHST- 2017/11/04 06:00 [pubmed]
PHST- 2018/08/31 06:00 [medline]
PHST- 2017/11/04 06:00 [entrez]
AID - S0378-5173(17)31035-9 [pii]
AID - 10.1016/j.ijpharm.2017.10.055 [doi]
PST - ppublish
SO  - Int J Pharm. 2018 Jan 15;535(1-2):38-46. doi: 10.1016/j.ijpharm.2017.10.055. Epub 
      2017 Oct 31.