Shear-stress sensitive lenticular vesicles for targeted drug delivery.
Atherosclerosis results in the narrowing of arterial blood vessels and this causes significant changes in the endogenous shear stress between healthy and constricted arteries. Nanocontainers that can release drugs locally with such rheological changes can be very useful. Here, we show that vesicles made from an artificial 1,3-diaminophospholipid are stable under static conditions but release their contents at elevated shear stress. These vesicles have a lenticular morphology, which potentially leads to instabilities along their equator. Using a model cardiovascular system based on polymer tubes and an external pump to represent shear stress in healthy and constricted vessels of the heart, we show that drugs preferentially release from the vesicles in constricted vessels that have high shear stress.
University of Geneva, Department of Organic Chemistry, Quai Ernest-Ansermet 30, 1211 Geneva, Switzerland.
Margaret N
MN
Holme
Illya A
IA
Fedotenko
Daniel
D
Abegg
Jasmin
J
Althaus
Lucille
L
Babel
France
F
Favarger
Renate
R
Reiter
Radu
R
Tanasescu
Pierre-Léonard
PL
Zaffalon
André
A
Ziegler
Bert
B
Müller
Till
T
Saxer
Andreas
A
Zumbuehl
D001158:Arteries / Q000187:drug effects / Q000473:pathology; D002319:Cardiovascular System / Q000187:drug effects*; D016503:Drug Delivery Systems; D004983:Ethanolamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008055:Lipids / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D012212:Rheology; D013314:Stress, Mechanical
C577072:1,3-dipalmitamidopropan-2-yl 2-(trimethylammonio)ethyl phosphate; D004983:Ethanolamines; D008055:Lipids; D010743:Phospholipids; C005448:phosphorylethanolamine