TY - JOUR
T1 - Site-directed decapsulation of bolaamphiphilic vesicles with enzymatic cleavable surface groups
AU - Popov, Mary
AU - Grinberg, Sarina
AU - Linder, Charles
AU - Waner, Tal
AU - Levi-Hevroni, Bosmat
AU - Deckelbaum, Richard J.
AU - Heldman, Eliahu
N1 - Funding Information:
This study was supported in the past by the Applied Research Fund for Biotechnology Research of BG Negev Technologies Ltd. , Ben-Gurion University and by a grant from the United States–Israel Binational Science Foundation No. 2003153 .
PY - 2012/6/10
Y1 - 2012/6/10
N2 - Stable nano-sized vesicles with a monolayer encapsulating membrane were prepared from novel bolaamphiphiles with choline ester head groups. The head groups were covalently bound to the alkyl chain of the bolaamphiphiles either via the nitrogen atom of the choline moiety, or via the choline ester's methyl group. Both types of bolaamphiphiles competed with acetylthiocholine for binding to acetylcholine esterase (AChE), yet, only the choline ester head groups bound to the alkyl chain via the nitrogen atom of the choline moiety were hydrolyzed by the enzyme. Likewise, only vesicles composed of bolaamphiphiles with head groups that were hydrolyzed by AChE released their encapsulated material upon exposure to the enzyme. Injection of carboxyfluorescein (CF)-loaded vesicles with cleavable choline ester head groups into mice resulted in the accumulation of CF in tissues that express high AChE activity, including the brain. By comparison, when vesicles with choline ester head groups that are not hydrolyzed by AChE were injected into mice, there was no accumulation of CF in tissues that highly express the enzyme. These results imply that bolaamphiphilic vesicles with surface groups that are substrates to enzymes which are highly expressed in target organs may potentially be used as a drug delivery system with controlled site-directed drug release.
AB - Stable nano-sized vesicles with a monolayer encapsulating membrane were prepared from novel bolaamphiphiles with choline ester head groups. The head groups were covalently bound to the alkyl chain of the bolaamphiphiles either via the nitrogen atom of the choline moiety, or via the choline ester's methyl group. Both types of bolaamphiphiles competed with acetylthiocholine for binding to acetylcholine esterase (AChE), yet, only the choline ester head groups bound to the alkyl chain via the nitrogen atom of the choline moiety were hydrolyzed by the enzyme. Likewise, only vesicles composed of bolaamphiphiles with head groups that were hydrolyzed by AChE released their encapsulated material upon exposure to the enzyme. Injection of carboxyfluorescein (CF)-loaded vesicles with cleavable choline ester head groups into mice resulted in the accumulation of CF in tissues that express high AChE activity, including the brain. By comparison, when vesicles with choline ester head groups that are not hydrolyzed by AChE were injected into mice, there was no accumulation of CF in tissues that highly express the enzyme. These results imply that bolaamphiphilic vesicles with surface groups that are substrates to enzymes which are highly expressed in target organs may potentially be used as a drug delivery system with controlled site-directed drug release.
KW - Acetylcholine
KW - Bolaamphiphiles
KW - Choline esterase
KW - Drug delivery
KW - Vesicles
UR - http://www.scopus.com/inward/record.url?scp=84861711784&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2011.12.022
DO - 10.1016/j.jconrel.2011.12.022
M3 - Article
C2 - 22226780
AN - SCOPUS:84861711784
SN - 0168-3659
VL - 160
SP - 306
EP - 314
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -