Delivery of interferon to intracellular pathways by encapsulation of interferon into multilamellar liposomes is independent of the status of interferon receptors

Killion, Jerald J.; Fishbeck, Randi; Bar‐Eli, Menashe; Chernajovsky, Yuti

doi:10.1016/1043-4666(94)90069-8

Cited by 14 publications

(5 citation statements)

References 27 publications

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“…This approach was found to reduce their toxicity, improve circulation time and antigen specific T-cell responses in comparison to free cytokines ( 126 , 127 ). Incorporation of granulocyte macrophage colony stimulating factor (GM-CSF) and interferon alpha (IFN-α) into nano-carriers exhibited great application in cancer therapy ( 128 , 129 ). Nano-carrier conjugated cytokines also showed great potential in the treatment of infectious diseases.…”

Section: Delivery Of Immune Stimulators Using Nanocarriersmentioning

confidence: 99%

Nanoparticle Vaccines Against Infectious Diseases

2018

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Due to emergence of new variants of pathogenic micro-organisms the treatment and immunization of infectious diseases have become a great challenge in the past few years. In the context of vaccine development remarkable efforts have been made to develop new vaccines and also to improve the efficacy of existing vaccines against specific diseases. To date, some vaccines are developed from protein subunits or killed pathogens, whilst several vaccines are based on live-attenuated organisms, which carry the risk of regaining their pathogenicity under certain immunocompromised conditions. To avoid this, the development of risk-free effective vaccines in conjunction with adequate delivery systems are considered as an imperative need to obtain desired humoral and cell-mediated immunity against infectious diseases. In the last several years, the use of nanoparticle-based vaccines has received a great attention to improve vaccine efficacy, immunization strategies, and targeted delivery to achieve desired immune responses at the cellular level. To improve vaccine efficacy, these nanocarriers should protect the antigens from premature proteolytic degradation, facilitate antigen uptake and processing by antigen presenting cells, control release, and should be safe for human use. Nanocarriers composed of lipids, proteins, metals or polymers have already been used to attain some of these attributes. In this context, several physico-chemical properties of nanoparticles play an important role in the determination of vaccine efficacy. This review article focuses on the applications of nanocarrier-based vaccine formulations and the strategies used for the functionalization of nanoparticles to accomplish efficient delivery of vaccines in order to induce desired host immunity against infectious diseases.

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Section: Delivery Of Immune Stimulators Using Nanocarriersmentioning

confidence: 99%

Nanoparticle Vaccines Against Infectious Diseases

2018

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“…Extracellularly added human IFNγ did not have an effect, since it does not recognize the extracellular domain of the mouse IFNγ receptor complex. Another study involved internalizing human IFNγ into mouse macrophages via a liposomal delivery system, resulting in induction of an antiproliferative effect (Killion et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

The role of IFNγ nuclear localization sequence in intracellular function

Ahmed

Burkhart

Mujtaba

et al. 2003

Journal of Cell Science

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IntroductionThe current view is that interferon γ (IFNγ) activates cells via interaction with the extracellular domain of the receptor complex (reviewed in Stark et al., 1998). This in turn results in the activation of the receptor-associated tyrosine kinases JAK1 and JAK2, leading to phosphorylation and dimerization of the transcription factor STAT1α, which dissociates from the receptor cytoplasmic domain and undergoes nuclear translocation. This current view ascribes no further role to IFNγ or the receptor chains IFNGR1 and IFNGR2 in IFNγ signaling. The above scenario ignores several events associated with IFNγ signaling. First, both IFNγ and one of the receptor chains, IFNGR1, undergo internalization or endocytosis and nuclear translocation Subramaniam et al., 2000). Second, at least three separate studies showed that intracellular IFNγ possessed biological activity that was qualitatively not unlike that of extracellular IFNγ. In one, microinjection of human IFNγ into mouse macrophage cells induced Ia expression (Smith et al., 1990). Extracellularly added human IFNγ did not have an effect, since it does not recognize the extracellular domain of the mouse IFNγ receptor complex. Another study involved internalizing human IFNγ into mouse macrophages via a liposomal delivery system, resulting in induction of an antiproliferative effect (Killion et al., 1994).Finally, intracellular expression of the human IFNγ gene in mouse fibroblasts in a non-secretory form resulted in induction of antiviral activity (Sanceau et al., 1987).Recently, we have determined the structural basis for nuclear translocation of murine IFNγ by identification of a polycationic nuclear localization sequence in its C-terminus (Subramaniam et al., 1999). Further, internalized IFNγ binds to the cytoplasmic domain of the IFNGR1 receptor chain . Immunoprecipitation experiments showed that a cytoplasmic complex of IFNγ-IFNGR1-STAT1α complexed to the nuclear importin α protein, NPI-1, occurs in an NLSdependent fashion . Thus, the internalization of IFNγ and nuclear transport of IFNγ and IFNGR1 appear to be a mechanism for nuclear import of the IFNγ transcription factor STAT1α.In the present study, we have expressed a non-secretable form of human IFNγ and found it to be biologically active. In order to demonstrate that the NLS of IFNγ was key to the intracellular events described above, positively charged amino acids in the NLS were replaced with alanines, such that the NLS sequence 128 KTGKRKR 134 was mutated to 128 ATGAAAA 134 . Non-secreted forms of IFNγ or its NLSmutated version were tested in murine and human cells for their ability to induce IFNγ activity, to activate STAT1α and to carry out nuclear translocation of STAT1α. The data show that

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“…[11][12][13][14][15] The use of liposomes as carriers of cytokines, 16 interleukin-2, 17 interleukin-7, 18 and interferon 19 has been reported, but that of Epo has not been studied in the past.…”

mentioning

confidence: 99%

Oral Administration of Recombinant Human Erythropoietin in Liposomes in Rats: Influence of Lipid Composition and Size of Liposomes on Bioavailability

Maitani

Hazama

Tojo

et al. 1996

Journal of Pharmaceutical Sciences

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Intestinal absorption of recombinant human erythropoietin (Epo) encapsulated in liposomes (Epo/liposomes) was examined by measuring the pharmacological effects of Epo after oral administration in rats. Circulating reticulocyte counts after oral administration of Epo/liposomes showed a profile different from that after intravenous administration. Epo/liposomes 0.1 micron in diameter were absorbed more effectively than those 0.2 micron in diameter. In the 0.1 micron Epo/liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and soybean-derived sterols (SS), cholesterol (Ch), or soybean-derived sterylglucosides (SG), DPPC/SS (in molar ratio 7/2) and DPPC/Ch (7/2) showed higher efficiency in intestinal absorption than DPPC/Ch (7/4) and DPPC/SG (7/2) at a low dose by the sysmex method. Pharmacological availabilities for oral administration of Epo/liposomes were 0.74-31% and 3.3-30% as evaluated by circulating reticulocyte counts and percentage circulating reticulocytes of erythrocytes, respectively, in comparison to those for intravenous administration of the same dose.

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Delivery of interferon to intracellular pathways by encapsulation of interferon into multilamellar liposomes is independent of the status of interferon receptors

Cited by 14 publications

References 27 publications

Nanoparticle Vaccines Against Infectious Diseases

Nanoparticle Vaccines Against Infectious Diseases

The role of IFNγ nuclear localization sequence in intracellular function

Oral Administration of Recombinant Human Erythropoietin in Liposomes in Rats: Influence of Lipid Composition and Size of Liposomes on Bioavailability

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