Conformational Stability of Human Interferon‐Gamma on Association with and Dissociation from Liposomes

Slooten, M. L. van; Visser, Antonie J. W. G.; Hoek, A. van; Storm, Gert; Crommelin, Daan J.A.; Jiskoot, Wim

doi:10.1002/1520-6017(200012)89:12<1605::aid-jps12>3.0.co;2-r

Cited by 17 publications

(4 citation statements)

References 32 publications

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“…However, the double-emulsion preparation method has been shown to cause protein degradation and denaturation [18] . Also, there might exist protein-liposomal bilayer interactions that may affect protein conformation and activity [19,20] . We used three methods to test protein chemical and structural changes after encapsulation.…”

Section: Discussionmentioning

confidence: 99%

“…Both the SDS-PAGE and HPLC analyses showed that the proteins were chemically intact. For protein conformational changes, some studies have used biophysical methods such as circular dichroism and fluorescence spectroscopy to detect the secondary structure or local amino acid environment changes [19] . We adopted a biochemical approach using an ELISA to probe possible 3-dimensional conformational changes.…”

Section: Discussionmentioning

confidence: 99%

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Multivesicular liposome formulations for the sustained delivery of interferon alpha-2b1

Qiu

Wei

Geng

et al. 2005

Acta Pharmacologica Sinica

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Aim: To develop and optimize a sustained release multivesicular liposome (MVL) formulation of interferon (IFN) α-2b. Methods: IFN α-2b MVL were prepared using a typical double-emulsion procedure. The sustained release effects of IFN α-2b MVL were investigated by monitoring the blood IFN α-2b concentration using an enzyme-linked immunosorbent assay test after subcutaneous administration to healthy mice. Results: IFN α-2b was successfully encapsulated in MVL with high efficiency, and the integrity of encapsulated protein was maintained. After subcutaneous injection, the MVL slowly released IFN α-2b into systemic circulation in a sustained manner. The estimated serum half-life of IFN α-2b was approximately 30 h. In addition, varying the size of the MVL preparations could further modify the in vivo release profile. Conclusion: IFN α-2b MVL may be a useful sustained release formulation in the clinical treatment of viral diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Multivesicular liposome formulations for the sustained delivery of interferon alpha-2b1

Qiu

Wei

Geng

et al. 2005

Acta Pharmacologica Sinica

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“…The finding that the effects of liposomal IFN-γ were dependent on its release and binding to extracellular membrane receptors emphasized that encapsulated cytokines must be released by their carrier outside the target cell to be effective [45]. Subsequent studies revealed that IFN-γ is encapsulated in liposomes primarily by electrostatic association with anionic lipids in the membrane and that the addition of cholesterol to the membrane increases liposome stability, which slows cytokine release [46–48]. Liposomal formulations that contained type I interferons and TNF-α have also been developed [49–52], with Eppstein and coworkers showing that anionic, multilamellar liposomes (MLVs) were most effective in encapsulating type I interferons compared with unilamellar and multilamellar liposomes with neutral or cationic surface charge.…”

Section: Characterization and Optimization Of Cytokine-loaded Particle mentioning

confidence: 99%

Particle-Mediated Delivery of Cytokines for Immunotherapy

Christian

Hunter

2012

Immunotherapy

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The ability of cytokines to direct the immune response to vaccination, infection and tumors has motivated their use in therapy to augment or shape immunity. To avoid toxic side effects associated with systemic cytokine administration, several approaches have been developed using particle-encapsulated cytokines to deliver this cargo to specific cell types and tissues. Initial work used cytokine-loaded particles to deliver proinflammatory cytokines to phagocytes to enhance antimicrobial and antitumor responses. These particles have also been used to create a cytokine depot at a local site to supplement prophylactic or antitumor vaccines or injected directly into solid tumors to activate immune cells to eliminate established tumors. Finally, recent advances have revealed that paracrine delivery of cytokines directly to T cells has the potential to enhance T-cell mediated therapies. The studies reviewed here highlight the progress in the last 30 years that has established the potential of particle-mediated cytokine immunotherapy.

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“…109 Of the studies to date, only van Slooten et al have examined IFN-g stability on desorption from the liposomes. 112 They found that the protein retained its secondary and tertiary structure on desorption, but examined a release period of just 30 min; therefore, long-term IFN-g stability in this formulation has yet to be demonstrated. Furthermore, the release period of the IFN-g from this liposomal formulation was relatively rapid, with a large burst of up to 75% of the initially loaded cytokine desorbed within the ®rst 8 h. 109 This release behavior has been noted with other proteins, such as interleukin-7, 113 in which $50% of the initial drug load was detectable in the urine of guinea pigs, and interleukin-2 which was detectable in the plasma for 6 h after administration by sc injection.…”

Section: Dosage Forms: Advantages and Limitationsmentioning

confidence: 99%

Interferon-γ therapy: Evaluation of routes of administration and delivery systems

Younes¹,

Amsden²

2002

J. Pharm. Sci.

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Although different routes and delivery systems have been used to deliver interferon-g (IFN-g) for the treatment of a variety of viral and neoplastic diseases, little has been reported regarding the most ef®cient and least toxic routes and drug delivery modes required to achieve these goals. To have a greater understanding of the best strategies to use to administer this cytokine in an ef®cient, stable, and safe manner, this review details aspects of IFN-g concerning its mechanism of action, physical properties, and pharmacokinetics. One important conclusion that is drawn from this analysis is that a consistent, local concentration of IFN-g is necessary to achieve an optimal therapeutic response. A critical discussion covering the advantages and limitations of the currently used methodologies to deliver IFN-g in such a fashion is presented. ß

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Conformational Stability of Human Interferon‐Gamma on Association with and Dissociation from Liposomes

Cited by 17 publications

References 32 publications

Multivesicular liposome formulations for the sustained delivery of interferon alpha-2b1

Multivesicular liposome formulations for the sustained delivery of interferon alpha-2b1

Particle-Mediated Delivery of Cytokines for Immunotherapy

Interferon-γ therapy: Evaluation of routes of administration and delivery systems

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