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Abstract

Prolonged presence of mIFNgamma at the site of antigen presentation is crucial for the generation of systemic immune responses in the B16 melanoma model. These studies show that liposomal encapsulation of cytokines is an attractive strategy for paracrine cytokine delivery in tumor vaccine development.

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

“…9 Due to electrostatic shielding of the negatively charged membrane, the positively charged protein is desorbed (>85%) from the liposome surface. The hIFN␥-containing medium was collected after ultracentrifugation and used for further study.…”

“…8 To improve its adjuvant activity, IFN␥ is encapsulated in liposomes to prevent rapid degradation and clearance after administration. 4,[8][9][10] The residence time of liposomal recombinant human IFN␥ (hIFN␥) at the site of injection in mice can be prolonged up to 7 days (i.e., a 19-fold increase compared with free hIFN␥) by modifying the location of the protein on the liposomal bilayer or the bilayer rigidity. 9 From a pharmaceutical and therapeutic point of view, it is evidently important to maintain the integrity of the protein during association with and after release from the liposomes.…”

“…4,[8][9][10] The residence time of liposomal recombinant human IFN␥ (hIFN␥) at the site of injection in mice can be prolonged up to 7 days (i.e., a 19-fold increase compared with free hIFN␥) by modifying the location of the protein on the liposomal bilayer or the bilayer rigidity. 9 From a pharmaceutical and therapeutic point of view, it is evidently important to maintain the integrity of the protein during association with and after release from the liposomes. 11 The interaction between the liposomal membrane and the protein should not lead to permanent conformational changes and subsequent unwanted biological effects, such as loss of activity or enhanced toxicity.…”

“…This interaction is primarily electrostatic in nature. 9 However, the protein can be partially embedded in the lipid bilayer, depending on the lipid composition of the bilayer and the presence of hydrophobic regions in the protein. 12,13 Both hydrophobic and electrostatic forces play an important role in the interaction between proteins and surfaces.…”

“…In contrast, interaction with neutral or positively charged liposomal membranes is much lower (5-20%). 9 In this paper, we study the conformational stability of hIFN␥ interacting with and after desorption from liposomal bilayers. We use hIFN␥ association with and dissociation from empty liposomes as a model for hIFN␥-containing liposomes prepared via the film hydration method.…”