Liposomes for phospholipase A2 triggered siRNA release: preparation and in vitro test
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Liposomes for phospholipase A2 triggered siRNA release: preparation and in vitro test. / Foged, Camilla; Nielsen, Hanne Mørck; Frøkjær, Sven.
I: Internation Journal of Pharmaceutics, Bind 331, Nr. 2, 2007, s. 160-166.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Liposomes for phospholipase A2 triggered siRNA release: preparation and in vitro test
AU - Foged, Camilla
AU - Nielsen, Hanne Mørck
AU - Frøkjær, Sven
PY - 2007
Y1 - 2007
N2 - Small interfering RNA (siRNA) is potent and highly specific for gene silencing. However, for therapeutic applications, delivery systems are required to protect siRNA from degradation, to enhance cellular uptake and for site-specific delivery. We used a double emulsion technique to encapsulate siRNA into stealth liposomes (SL) to increase entrapment efficiency compared to passive encapsulation. SL are designed for localized, active release of siRNA by secretory phosholipase A2 (sPLA2). sPLA2 acts as a site-specific enzymatic trigger that actively degrades the liposomal carrier in inflamed tissue releasing entrapped drug. Relatively good encapsulation efficiencies compared to passive encapsulation were demonstrated (7–9%) and SL size was appropriate for i.v. administration (60–90 nm). siRNA targeting enhanced green fluorescent protein (EGFP) entrapped in SL did not silence gene expression of HeLa-cells stably expressing EGFP. However, preliminary flow cytometry and confocal microscopy data showed that the SL siRNA formulation increased uptake of siRNA into vesicular compartments of HeLa-cells in a concentration-dependent manner that could be augmented by exogenuos sPLA2. We hypothesize that the SL can be used to target siRNA to inflammed tissue for silencing of cytokine expression in rheumatoid arthritis.
AB - Small interfering RNA (siRNA) is potent and highly specific for gene silencing. However, for therapeutic applications, delivery systems are required to protect siRNA from degradation, to enhance cellular uptake and for site-specific delivery. We used a double emulsion technique to encapsulate siRNA into stealth liposomes (SL) to increase entrapment efficiency compared to passive encapsulation. SL are designed for localized, active release of siRNA by secretory phosholipase A2 (sPLA2). sPLA2 acts as a site-specific enzymatic trigger that actively degrades the liposomal carrier in inflamed tissue releasing entrapped drug. Relatively good encapsulation efficiencies compared to passive encapsulation were demonstrated (7–9%) and SL size was appropriate for i.v. administration (60–90 nm). siRNA targeting enhanced green fluorescent protein (EGFP) entrapped in SL did not silence gene expression of HeLa-cells stably expressing EGFP. However, preliminary flow cytometry and confocal microscopy data showed that the SL siRNA formulation increased uptake of siRNA into vesicular compartments of HeLa-cells in a concentration-dependent manner that could be augmented by exogenuos sPLA2. We hypothesize that the SL can be used to target siRNA to inflammed tissue for silencing of cytokine expression in rheumatoid arthritis.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1016/j.ijpharm.2006.11.010
DO - 10.1016/j.ijpharm.2006.11.010
M3 - Journal article
VL - 331
SP - 160
EP - 166
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 2
ER -
ID: 2340647