Liposome—complement interactions in rat serum: implications for liposome survival studies

Devine, Dana V.; Wong, Kenneth; Serrano, Katherine; Chonn, Arcadio; Cullis, Pieter R.

doi:10.1016/0005-2736(94)90231-3

Cited by 227 publications

(128 citation statements)

References 21 publications

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“…Thus, it is likely that the acute clinical adverse reactions observed in this work were consequence of the action of anaphylatoxins (C3a and C5a) released after activation of the complement cascade by the lipid vesicles. There is extensive literature on complement system activation by liposomes (Devine et al 1994, Liu et al 1995, Szebeni 2005. Natural antibodies against phospholipids and cholesterol are present in all animal species (Wassef et al 1989) and the binding of these proteins to lipids of liposomes would allow the activation of complement through the classic route (Liu et al 1995).…”

Section: Discussionmentioning

confidence: 99%

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Complement activation-related pseudoallergy in dogs following intravenous administration of a liposomal formulation of meglumine antimoniate

et al. 2013

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Pesq. Vet. Bras. 33(8):1016Bras. 33(8): -1020Bras. 33(8): , agosto 2013Bras. 33(8): 1016 RESUMO.-[Pseudoalergia relacionada à ativação do complemento em cães após administração intravenosa de uma formulação lipossomal de antimoniato de meglumina.] O crescente uso das nanotecnologias nas terapias avançadas tem permitido a observação de reações adversas específicas relacionadas às nanoestruturas. A toxicidade de uma nova formulação lipossomal de antimoniato de meglumina após dose única foi avaliada em cães com leishmaniose visceral. The increasing use of nanotechnologies in advanced therapies has allowed the observation of specific adverse reactions related to nanostructures. The toxicity of a novel liposome formulation of meglumine antimoniate in dogs with visceral leishmaniasis after single dose has been investigated. Groups of 12 animals received by the intravenous route a single dose of liposomal meglumine antimoniate (group I [GI], 6.5 mg Sb/kg), empty liposomes (GII) or isotonic saline (GIII). Evaluation of hematological and biochemical parameters showed no significant changes 4 days after administration. No undesired effects were registered in the GIII. However, adverse reactions were observed in 67.7% of dogs from both groups that received liposomal formulations. The side effects began moments after bolus administration and disappeared during the first 15 minutes after treatment. Prostation, sialorrhea and defecation were the most frequent clinical signs, registered in 33.3% and 41.6 % of animals from the groups GI and GII, respectively. Tachypnea, mydriasis, miosis, vomiting and cyanosis were also registered in both groups. The adverse reactions observed in this study were attributed to the activation of the complement system by lipid vesicles in a phenomenon known as Complement Activation-Related Pseudoallergy (CARPA). The influence of the physical-chemical characteristics of liposomal formulation in the triggering of CARPA is discussed.

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Section: Discussionmentioning

confidence: 99%

“…Although the activation of complement appears to be an intrinsic property of lipid bilayers formed by cholesterol and electrically charged phospholipids (Devine et al 1994), laboratory changes associated of systems carriers of drugs can be observed in the absence of clinical effects (Valladares et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Complement activation-related pseudoallergy in dogs following intravenous administration of a liposomal formulation of meglumine antimoniate

et al. 2013

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“…Both leukocytes and phagocytic cells of the reticuloendothelial system bind liposomes in a process that is at least in part complement dependent and influenced by the membrane lipid composition. 12,13,29 Complement-mediated uptake is greater for charged than for neutral liposomes. 13,29 Our results indicate that anionic lipid microbubbles similarly attach to activated leukocytes in a complement-dependent fashion.…”

Section: Mediators Of Microbubble/leukocyte Interactionsmentioning

confidence: 99%

“…12,13,29 Complement-mediated uptake is greater for charged than for neutral liposomes. 13,29 Our results indicate that anionic lipid microbubbles similarly attach to activated leukocytes in a complement-dependent fashion. The enhanced binding of lipid microbubbles when leukocytes were activated with PMA is consistent with known inducible surface expression of complement receptors.…”

Section: Mediators Of Microbubble/leukocyte Interactionsmentioning

confidence: 99%

Microbubble Persistence in the Microcirculation During Ischemia/Reperfusion and Inflammation Is Caused by Integrin- and Complement-Mediated Adherence to Activated Leukocytes

et al. 2000

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Background-Albumin microbubbles that are used for contrast echocardiography persist within the myocardial microcirculation after ischemia/reperfusion (I-R). The mechanism responsible for this phenomenon is unknown. Methods and Results-Intravital microscopy of the microcirculation of exteriorized cremaster muscle was performed in 12 wild-type mice during intravenous injections of fluorescein-labeled microbubbles composed of albumin, anionic lipids, or cationic lipids. Injections were performed at baseline and after 30 to 90 minutes of I-R in 8 mice and 2 hours after intrascrotal tumor necrosis factor-␣ (TNF-␣) in 4 mice. Microbubble adherence at baseline was uncommon (Ͻ2/50 high-power fields). After I-R, adherence increased (PϽ0.05) to 9Ϯ5 and 5Ϯ4 per 50 high-power fields for albumin and anionic lipid microbubbles, respectively, due to their attachment to leukocytes adherent to the venular endothelium. TNF-␣ produced even greater microbubble binding, regardless of the microbubble shell composition. The degree of microbubble attachment correlated (rϭ0.84 to 0.91) with the number of adhered leukocytes. Flow cytometry revealed that microbubbles preferentially attached to activated leukocytes. Albumin microbubble attachment was inhibited by blocking the leukocyte ␤ 2 -integrin Mac-1, whereas lipid microbubble binding was inhibited when incubations were performed in complement-depleted or heat-inactivated serum rather than control serum. Conclusions-Microvascular attachment of albumin and lipid microbubbles in the setting of I-R and TNF-␣-induced inflammation is due to their ␤ 2 -integrin-and complement-mediated binding to activated leukocytes adherent to the venular wall. Thus, microbubble persistence on contrast ultrasonography may be useful for the detection and monitoring of leukocyte adhesion in inflammatory diseases. (Circulation. 2000;101:668-675.)

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“…The RES clears larger sized nanoparticles by means of Kupffer cells and macrophages [85]. Nanoparticles larger than 100 nm are reported to activate the classical complement pathway and macrophage internalization, both in a size dependent manner, with larger particles being recognized and cleared the fastest; however, the exact nanoparticle formulation as well as the surface charge also affects the rate of the mononuclear phagocyte clearance [99], [100]. Therefore, nanoparticles larger than 10 nm but smaller than 100 nm are considered to be in the ideal size range to evade both renal and RES clearance mechanisms long enough to benefit from EPR enhanced delivery.…”

Section: The Men Clearance Mechanismmentioning

confidence: 99%

Targeted and Controlled Anticancer Drug Delivery and Release with Magnetoelectric Nanoparticles

Rodzinski¹

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Liposome—complement interactions in rat serum: implications for liposome survival studies

Cited by 227 publications

References 21 publications

Complement activation-related pseudoallergy in dogs following intravenous administration of a liposomal formulation of meglumine antimoniate

Complement activation-related pseudoallergy in dogs following intravenous administration of a liposomal formulation of meglumine antimoniate

Microbubble Persistence in the Microcirculation During Ischemia/Reperfusion and Inflammation Is Caused by Integrin- and Complement-Mediated Adherence to Activated Leukocytes

Targeted and Controlled Anticancer Drug Delivery and Release with Magnetoelectric Nanoparticles

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