PMID- 25540904
OWN - NLM
STAT- MEDLINE
DCOM- 20151123
LR  - 20181202
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 201
DP  - 2015 Mar 10
TI  - Mechanistic profiling of the siRNA delivery dynamics of lipid-polymer hybrid 
      nanoparticles.
PG  - 22-31
LID - S0168-3659(14)00823-2 [pii]
LID - 10.1016/j.jconrel.2014.12.026 [doi]
AB  - Understanding the delivery dynamics of nucleic acid nanocarriers is fundamental 
      to improve their design for therapeutic applications. We investigated the carrier 
      structure-function relationship of lipid-polymer hybrid nanoparticles (LPNs) 
      consisting of poly(DL-lactic-co-glycolic acid) (PLGA) nanocarriers modified with 
      the cationic lipid dioleoyltrimethyl-ammoniumpropane (DOTAP). A library of 
      siRNA-loaded LPNs was prepared by systematically varying the 
      nitrogen-to-phosphate (N/P) ratio. Atomic force microscopy (AFM) and 
      cryo-transmission electron microscopy (cryo-TEM) combined with small angle X-ray 
      scattering (SAXS) and confocal laser scanning microscopy (CLSM) studies suggested 
      that the siRNA-loaded LPNs are characterized by a core-shell structure consisting 
      of a PLGA matrix core coated with lamellar DOTAP structures with siRNA localized 
      both in the core and in the shell. Release studies in buffer and serum-containing 
      medium combined with in vitro gene silencing and quantification of intracellular 
      siRNA suggested that this self-assembling core-shell structure influences the 
      siRNA release kinetics and the delivery dynamics. A main delivery mechanism 
      appears to be mediated via the release of transfection-competent siRNA-DOTAP 
      lipoplexes from the LPNs. Based on these results, we suggest a model for the 
      nanostructural characteristics of the LPNs, in which the siRNA is organized in 
      lamellar superficial assemblies and/or as complexes entrapped in the polymeric 
      matrix.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Colombo, Stefano
AU  - Colombo S
AD  - Department of Pharmacy, Faculty of Health and Medical Sciences, University of 
      Copenhagen, Universitetsparken 2, 2100 Copenhagen O, Denmark.
FAU - Cun, Dongmei
AU  - Cun D
AD  - Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 
      Shenyang, Wenhua Road 103, 110016, China. Electronic address: cundongmei@163.com.
FAU - Remaut, Katrien
AU  - Remaut K
AD  - Biophotonic Imaging Group, Lab of General Biochemistry and Physical Pharmacy, 
      Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
FAU - Bunker, Matt
AU  - Bunker M
AD  - Molecular Profiles Ltd, 8 Orchard Place, Nottingham Business Park, Nottingham NG8 
      6PX, UK.
FAU - Zhang, Jianxin
AU  - Zhang J
AD  - Molecular Profiles Ltd, 8 Orchard Place, Nottingham Business Park, Nottingham NG8 
      6PX, UK.
FAU - Martin-Bertelsen, Birte
AU  - Martin-Bertelsen B
AD  - Department of Pharmacy, Faculty of Health and Medical Sciences, University of 
      Copenhagen, Universitetsparken 2, 2100 Copenhagen O, Denmark.
FAU - Yaghmur, Anan
AU  - Yaghmur A
AD  - Department of Pharmacy, Faculty of Health and Medical Sciences, University of 
      Copenhagen, Universitetsparken 2, 2100 Copenhagen O, Denmark.
FAU - Braeckmans, Kevin
AU  - Braeckmans K
AD  - Biophotonic Imaging Group, Lab of General Biochemistry and Physical Pharmacy, 
      Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium; Centre for Nano- and 
      Biophotonics, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
FAU - Nielsen, Hanne M
AU  - Nielsen HM
AD  - Department of Pharmacy, Faculty of Health and Medical Sciences, University of 
      Copenhagen, Universitetsparken 2, 2100 Copenhagen O, Denmark. Electronic address: 
      hanne.morck@sund.ku.dk.
FAU - Foged, Camilla
AU  - Foged C
AD  - Department of Pharmacy, Faculty of Health and Medical Sciences, University of 
      Copenhagen, Universitetsparken 2, 2100 Copenhagen O, Denmark.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141223
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Fatty Acids, Monounsaturated)
RN  - 0 (Quaternary Ammonium Compounds)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - MR86K0XRQP (1,2-dioleoyloxy-3-(trimethylammonium)propane)
SB  - IM
MH  - Cell Line, Tumor
MH  - Fatty Acids, Monounsaturated/chemistry
MH  - Green Fluorescent Proteins/genetics
MH  - Humans
MH  - Lactic Acid/chemistry
MH  - Nanoparticles/*administration & dosage/chemistry
MH  - Polyglycolic Acid/chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Quaternary Ammonium Compounds/chemistry
MH  - RNA, Small Interfering/*administration & dosage/chemistry
OTO - NOTNLM
OT  - DOTAP
OT  - Drug delivery
OT  - Nanomedicine
OT  - PLGA
OT  - Sustained release
OT  - siRNA
EDAT- 2014/12/30 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/12/27 06:00
PHST- 2014/10/31 00:00 [received]
PHST- 2014/12/19 00:00 [revised]
PHST- 2014/12/20 00:00 [accepted]
PHST- 2014/12/27 06:00 [entrez]
PHST- 2014/12/30 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S0168-3659(14)00823-2 [pii]
AID - 10.1016/j.jconrel.2014.12.026 [doi]
PST - ppublish
SO  - J Control Release. 2015 Mar 10;201:22-31. doi: 10.1016/j.jconrel.2014.12.026. 
      Epub 2014 Dec 23.