Surface modification of liposomes for selective cell targeting in cardiovascular drug delivery.
Cardiovascular disease processes such as atherosclerosis, restenosis, and inflammation are typically localized to discrete regions of the vasculature, affording great opportunity for targeted pharmacological treatment. Liposomes are potentially advantageous targeted drug carriers for such intravascular applications. To facilitate their use as drug delivery vehicles, we have considered three components of liposome design: (i) identification of candidate cell surface receptors for targeting; (ii) identification of ligands that maintain binding specificity and affinity; and (iii) prevention of rapid nonspecific clearance of liposomes into the reticuloendothelial organs. In this report, we describe our work in developing liposomal surface modifications that address both targeting and clearance. An arginine-glycine-aspartic acid (RGD) containing peptide was used as a model ligand to target liposomes to the integrin GPIIb-IIIa on activated platelets. Additionally, oligodextran surfactants incorporated into liposomes provided insight into the effect of vesicle perturbations on liposome clearance, and the importance of molecular geometry in designing oligosaccharide surface modifications. Together these studies demonstrate the feasibility of using peptides to guide liposomes to desired receptors, and illustrate the influence of vesicle stability on liposome interactions in vivo. Furthermore, they underscore the importance of simultaneously considering both targeting specificity and vesicle longevity in the design of effective targeted drug delivery systems.
Lestini
Brian J
BJ
Department of Biomedical Engineering, Case Western Reserve University, Wickenden Building, 10900 Eluclid Avenue, Cleveland, OH 44106, USA.
Sagnella
Sharon M
SM
Xu
Zhong
Z
Shive
Matthew S
MS
Richter
Nancy J
NJ
Jayaseharan
Johnsamuel
J
Case
Aubrey J
AJ
Kottke-Marchant
Kandice
K
Anderson
James M
JM
Marchant
Roger E
RE
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D003911:Dextrans / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005260:Female; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000008:administration & dosage*; D009844:Oligosaccharides / Q000008:administration & dosage*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000008:administration & dosage
D003911:Dextrans; D008081:Liposomes; D009842:Oligopeptides; D009844:Oligosaccharides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C047981:arginyl-glycyl-aspartic acid