Highly efficient immunoliposomes prepared with a method which is compatible with various lipid compositions

Holmberg, Eric G.; Maruyama, Kazuo; Litzinger, David C.; Wright, Stephen E.; Davis, M.A.F.; Kabalka, George W.; Kennel, Stephen J.; Huang, Leaf

doi:10.1016/0006-291x(89)92740-x

Cited by 62 publications

(14 citation statements)

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“…This convenient model has allowed us to investigate the effect on target binding of some physical parameters of liposomes such as antibody/lipid ratio, liposome size, and injection dose (8). Under optimal conditions, it was found that up to 60% of the injected immunoliposomes were bound to the lung target; the uptake of immunoliposomes by liver and spleen, the major reticuloendothelial system (RES), was only about 12% (9).…”

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confidence: 99%

“…This lipophilic radiolabel is not transferred to the serum components from liposomes (K.M. and L.H., unpublished data), and it is not rapidly metabolized in vivo (9). The synthesis of N-glutaryl phosphatidylethanolamine (NGPE) has been described (18).…”

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confidence: 99%

“…Since gp112 is located exclusively and abundantly on the lumenal surface of the pulmonary capillary vessel wall (6, 7), i.v. injected immunoliposomes gain direct access and bind efficiently to the lung target (5,8,9). This convenient model has allowed us to investigate the effect on target binding of some physical parameters of liposomes such as antibody/lipid ratio, liposome size, and injection dose (8).…”

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confidence: 99%

“…Highly efficient target binding and a relatively low level of RES uptake of the immunoliposomes described above seemingly violate this rule. Furthermore labeled DTPA-SA ("1In-DTPA-SA) was prepared as described (9). Briefly, 1 1.l of 111InCl3 (carrier-free, New England Nuclear) and 600 Al of 1 mM DTPA-SA, which was dissolved in hot (-650C) ethanol with brief sonication, were mixed to form the 1In-DTPA-SA complex.…”

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Lipid composition is important for highly efficient target binding and retention of immunoliposomes.

Maruyama

Kennel

Huang

1990

Proc. Natl. Acad. Sci. U.S.A.

154

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By taking advantage of a monoclonal IgG antibody, 34A, which is highly specific to pulmonary endothelial cells, we have prepared liposomes containing various amounts of antibody molecules (immunoliposomes). These immunoliposomes accumulate specifically in the lung when injected i.v. Two lipid compositions were used: phosphatidylcholine/cholesterol/phosphatidylserine (PS), 10:5:1 (mol/mol), a composition that allows liposomes to be readily taken up by the reticuloendothelial system (RES) (liver and spleen), and phosphatidylcholine/cholesterol/ganglioside GM,, 10:5:1 (mol/mol), a composition that allows liposomes to avoid or delay the RES uptake (the so-called stealth liposomes). Although an increase in the number of antibody molecules per liposome was accompanied by an increased level of lung binding of the immunoliposomes, differences due to the lipid composition were more profound. For example, stealth immunoliposomes containing an antibody/lipid ratio = 1:37 (wt/wt) accumulated in lung to a level of 60% of the injected dose, whereas PS-containing immunoliposomes with a higher antibody/lipid ratio (1:8) only accumulated 50% of the injected dose in the lung. Conjugation of antibody to the stealth liposome did not increase the rate of liposome uptake by liver; this rate was approximately 10-fold lower than that of the PS-containing liposomes without antibody. Stealth Immunoliposomes with high antibody content also showed long retention in the lung. The th of lung residence for the stealth immunoliposomes with an antibody/lipid ratio = 1:11 (wt/wt) was =24 hr. The fact that stealth immunoliposomes showed a longer retention time in the lung than the PS-containing immunoliposomes of similar antibody content suggests that macrophages may play a role in the removal of the bound immunoliposomes from the pulmonary endothelium. Alternatively, dissociated stealth immunoliposomes may reenter the circulation and rebind to the lung target, causing an apparent slow overall dissociation rate. These results can be understood on the basis of two competing kinetic processes: lung binding whose rate is directly proportional to the antibody content of the immunoliposomes and uptake by RES whose rate is significantly reduced in the case of the stealth liposomes. Even for a modest level of antibody content, the half-life for target binding of immunoliposomes was significantly horter than the half-life of liver uptake of the liposomes, resulting in a favorable target binding. Significant immunoliposome binding to the lung is not due to the fact that tail vein-injected liposomes flow through the lung capillary bed before they encounter the liver, because portal vein-injected immunoliposomes showed the same rate and extent of target binding as the tail vein-injected ones.

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Lipid composition is important for highly efficient target binding and retention of immunoliposomes.

Maruyama

Kennel

Huang

1990

Proc. Natl. Acad. Sci. U.S.A.

154

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“…Liposomes were prepared by the detergent-dialysis method, 21,22 originally developed for the reconstitution of membrane proteins, using the detergent OG. The protein was first conjugated to NGPE in the presence of detergent.…”

Section: Preparation Of Liposomesmentioning

confidence: 99%

Reconstitution of adhesive properties of human platelets in liposomes carrying both recombinant glycoproteins Ia/IIa and Ibα under flow conditions: specific synergy of receptor–ligand interactions

Nishiya

Kainoh

Murata

et al. 2002

Blood

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Liposomes carrying both recombinant glycoprotein Ia/IIa (rGPIa/IIa) and Ib␣ (rGPIb␣) (rGPIa/IIa-Ib␣-liposomes) instantaneously and irreversibly adhered to the collagen surface in the presence of soluble von Willebrand factor (VWF) at high shear rates, in marked contrast with translocation of liposomes carrying rGPIb␣ alone on the VWF surface. In the absence of soluble VWF, the adhesion of rGPIa/IIa-Ib␣-liposomes to the collagen surface decreased with increasing shear rates, similar to liposomes carrying rGPIa/ IIa alone. While adhesion of liposomes with exofacial rGPIa/IIa and rGPIb␣ densities of 2.17 ؋ 10 3 and 1.00 ؋ 10 4 molecules per particle, respectively, was efficient at high shear rates, reduction in rGPIb␣ density to 5.27 ؋ 10 3 molecules per particle resulted in decreased adhesion even in the presence of soluble VWF. A 50% reduction in the exofacial rGPIa/IIa density resulted in a marked decrease in the adhesive ability of the liposomes at all shear rates tested. The inhibitory effect of antibody against GPIb␣ (GUR83-35) on liposome adhesion was greater at higher shear rates. Further, the anti-GPIa antibody (Gi9) inhibited liposome adhesion more than GUR83-35 at all shear rates tested. These results suggest that the rGPIa/IIa-collagen interaction dominates the adhesion of rGPIa/IIa-Ib␣-liposomes to the collagen surface at low shear rates, while the rGPIa/IIa-collagen and rGPIb␣-VWF interaction complements each other, and they synergistically provide the needed functional integration required for liposome adhesion at high shear rates. This study thus has confirmed for the first time the proposed mechanisms of platelet adhesion to the collagen surface under flow conditions using the liposome system. IntroductionThe basic and important platelet functions for primary hemostasis are adhesion and aggregation, and this can be easily understood from the observations that patients with congenital platelet membrane defects such as Bernard-Soulier syndrome or Glanzmann thrombasthenia are deficient in platelet adhesion or aggregation and have severe bleeding tendencies. The contribution of specific platelet receptors or adhesive proteins to platelet adhesion and aggregation onto immobilized collagen under flow conditions is usually studied with monoclonal antibodies or inhibitors specific to particular platelet receptors or adhesive proteins or, also, with blood from patients with congenital bleeding disorders deficient in specific receptors or adhesive proteins. These analyses indicate that initial platelet adhesion depends on the interaction of glycoprotein (GP) Ib/IX/V complexes on platelets with von Willebrand factor (VWF) adsorbed on the collagen surface. This is a rapid but low-affinity interaction, suggesting that it serves to tether platelets, flowing at high speed in the bloodstream, to the collagen surface. [1][2][3][4] The collagen receptors of the tethered platelets then bind strongly with the collagen surface, activating platelets to form aggregates. This was supported by observations that platelets ...

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Immunoliposomes for Specific Drug Delivery

Calin¹

2012

Antibody‐Mediated Drug Delivery Systems

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Highly efficient immunoliposomes prepared with a method which is compatible with various lipid compositions

Cited by 62 publications

References 10 publications

Lipid composition is important for highly efficient target binding and retention of immunoliposomes.

Lipid composition is important for highly efficient target binding and retention of immunoliposomes.

Reconstitution of adhesive properties of human platelets in liposomes carrying both recombinant glycoproteins Ia/IIa and Ibα under flow conditions: specific synergy of receptor–ligand interactions

Immunoliposomes for Specific Drug Delivery

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