Liposomes as sustained release system for human interferon-γ: biopharmaceutical aspects

Slooten, M. L. van; Boerman, Otto C.; Romøren, Kristine; Kedar, Eli; Crommelin, Daan J.A.; Storm, Gert

doi:10.1016/s1388-1981(00)00174-8

Cited by 68 publications

(39 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast to interleukin-2 and interferon-gamma, which associate to liposomes by simple electrostatic, nontransforming interactions, rh-Epo binds with defined positively charged amino acids, as demonstrated by experiments with carbamylated rh-Epo (Koppenhagen et al, 1998a(Koppenhagen et al, , 1998bKuboi et al, 2000;Van Slooten et al, 2001;Zschörnig et al, 2005). Within these examinations, the positively charged lysines and arginines were neutralized by carbamylation, which results in the deprivation of the membrane-modulating activity of rh-Epo (Arcasoy, 2008;Brines et al, 2004;Leist et al, 2004;Tilbrook and Klinken, 1999;Wang et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

“…However, the electrostatic attraction alone cannot explain the formation of discoid structures, because simple adsorption is insufficient to interrupt membrane structures, as reported for interleukin-2 and interferon-gamma (Koppenhagen et al, 1998b;Van Slooten et al, 2001;Kuboi et al, 2000;Nomura et al, 2001;Sevcsik et al, 2007Sevcsik et al, , 2008Takiguchi et al, 2002). Thus, the effect of the protein structure was examined by applying DTT-treated rh-Epo to EPG-ULVs.…”

Section: Resultsmentioning

confidence: 99%

“…This association is predominantly reversible without the destruction of proteins or membranes (Koppenhagen et al, 1998b;Van Slooten et al, 2001). Membrane transformation is only induced if additional conformational changes of the protein occur and a penetrating sequence is interacting with the membrane.…”

Section: Resultsmentioning

confidence: 99%

“…Multilamellar vesicles (MLVs) were prepared by the classical film rehydration method with various lipid compositions (HSPC, DOTAP, EGP, and EPG LOW ), as shown in Table 1 (Kasi et al, 1984;Perez-Soler et al, 1985;Van Slooten et al, 2001;Walde and Ichikawa 2001). Lipids (8-12 mg/mL) were dissolved in 10-30 mL of chloroform, and the solvent was vacuum evaporated while rotating at 35°C in a water bath.…”

Section: Preparation Of Liposomesmentioning

confidence: 99%

See 3 more Smart Citations

Topological transformation of liposomes by a membrane-affecting domain of recombinant human erythropoietin

Strobach¹,

Kunert²,

Stadlmann³

et al. 2009

Journal of Liposome Research

View full text Add to dashboard Cite

Recombinant human erythropoietin (rh-Epo) is well accepted as a hematopoietic drug, but many other pleiotropic properties are currently under investigation. Rh-Epo-induced receptor-mediated signal transductions are accompanied with membrane dynamic processes, which facilitate the activation of individual pathways. However, its direct effect on membrane dynamics is still unknown. In the present study, we have proven the capability of rh-Epo to associate to and transform artificial lipid membranes. Association studies using neutral, negatively, and positively charged liposomes with the native as well as modified rh-Epo were performed and analyzed by transmission electron microscopy and differential scanning calorimetry. By these studies, we demonstrated that rh-Epo has the capability to transform negatively charged unilamellar vesicles into so-called disc-like micelles. Rh-Epo association to the negatively charged head groups via lysine and arginine initiates this transformation. At physiological temperatures, conformational changes within the rh-Epo structure expose a defined amino-acid sequence, which is able to induce the formation of discoid membrane structures. Enzymatic digestion, analysis, and isolation of related peptides by rp-HPLC and characterization by MS/MS enabled the identification of the membrane-affecting domain of rh-Epo (MAD-E) that represents the exposed helix B of rh-Epo. Finally, association studies performed with these peptides confirmed that the MAD-E is responsible for the formation of disc-like micelles. Since this helix B of rh-Epo has recently been supposed to be involved in the activation of neuroprotective pathways, we believe that the membrane-transforming capacity of rh-Epo participates in the proliferative activity of rh-Epo.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Preparation Of Liposomesmentioning

confidence: 99%

See 2 more Smart Citations

Topological transformation of liposomes by a membrane-affecting domain of recombinant human erythropoietin

Strobach¹,

Kunert²,

Stadlmann³

et al. 2009

Journal of Liposome Research

View full text Add to dashboard Cite

show abstract

“…32 Liposomes have been widely and successfully used as a continuous and controlled-release system for various drugs, including protein drugs and small-molecule drugs (for example, interferon-γ and cisplatin). 13,14 However, the sustained release of liposomes is not satisfactory, since the membrane of liposomes is soft and easily ruptured. 15,16 Further, the cholesterol and phospholipid exchange between liposomes and other membranes could easily occur, resulting in the destabilization of liposomes and drug release from liposomes.…”

mentioning

confidence: 99%

Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth

Guo

Zhu

Liu

et al. 2017

IJN

View full text Add to dashboard Cite

Purpose To reduce the adverse effects and high frequency of administration of propranolol to treat infantile hemangioma, we first utilized propranolol-loaded liposomes-in-microsphere (PLIM) as a novel topical release system to realize sustained release of propranolol. Methods PLIM was developed from encapsulating propranolol-loaded liposomes (PLs) in microspheres made of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) copolymers (PLGA-PEG-PLGA). The release profile of propranolol from PLIM was evaluated, and its biological activity was investigated in vitro using proliferation assays on hemangioma stem cells (HemSCs). Tumor inhibition was studied in nude mice bearing human subcutaneous infantile hemangioma. Results The microspheres were of desired particle size (~77.8 μm) and drug encapsulation efficiency (~23.9%) and achieved sustained drug release for 40 days. PLIM exerted efficient inhibition of the proliferation of HemSCs and significantly reduced the expression of two angiogenesis factors (vascular endothelial growth factor-A [VEGF-A] and basic fibroblast growth factor [bFGF]) in HemSCs. Notably, the therapeutic effect of PLIM in hemangioma was superior to that of propranolol and PL in vivo, as reflected by significantly reduced hemangioma volume, weight, and microvessel density. The mean hemangioma weight of the PLIM-treated group was significantly lower than that of other groups (saline =0.28 g, propranolol =0.21 g, PL =0.13 g, PLIM =0.03 g; PLIM vs saline: P <0.001, PLIM vs propranolol: P <0.001, PLIM vs PL: P <0.001). The mean microvessel density of the PLIM-treated group was significantly lower than that of other groups (saline =40 vessels/mm 2 , propranolol =31 vessels/mm 2 , PL =25 vessels/mm 2 , PLIM =11 vessels/mm 2 ; PLIM vs saline: P <0.001, PLIM vs propranolol: P <0.01, PLIM vs PL: P <0.05). Conclusion Our findings show that PLIM is a very promising approach to locally and efficiently deliver propranolol to the hemangioma site leading to a significant inhibition of infantile hemangioma.

show abstract

Idiotype vaccination for Non-Hodgkin lymphoma

Ossendorf¹,

Cornely

Draube

et al. 2011

Cochrane Database of Systematic Reviews

View full text Add to dashboard Cite

Liposomes as sustained release system for human interferon-γ: biopharmaceutical aspects

Cited by 68 publications

References 21 publications

Topological transformation of liposomes by a membrane-affecting domain of recombinant human erythropoietin

Topological transformation of liposomes by a membrane-affecting domain of recombinant human erythropoietin

Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth

Idiotype vaccination for Non-Hodgkin lymphoma

Contact Info

Product

Resources

About