Continuous Release of Interleukin-2 from Liposomal IL-2 (Mixture of Interleukin-2 and Liposomes) After Subcutaneous Administration to Mice

Abstract

Recombinant interleukin-2 (IL-2) was strongly and almost completely adsorbed onto small and hydrophobic liposomes by simple mixing under optimal conditions (liposome: DSPC-DSPG; molar ratio, 10:1; 30-50 nm in size, ratio of IL-2 to liposome: 4.0 JRU/nmol lipid). This liposomal IL-2 displayed better distribution after intravenous administration in mice and improved therapeutic effect against experimental M5076 metastases, as reported previously. In this study, the elimination of IL-2 from the dosing area was investigated when the liposomal IL-2 was administered to mice subcutaneously. The results suggest that the release of IL-2 from this liposome was continuous and almost complete. The mean residence time (MRT) of IL-2 in the dosing area was 11.0 +/- 1.65 hr. This resulted in the 8-fold times enhancement of MRT in the systemic circulation by the presence of liposomes, and IL-2 was detected in the serum for 2 days. Using this liposomal IL-2 is expected to have the potential to decrease the number of injections and enhance the efficacy of IL-2 in immunotherapies and therapies against tumor.

Exploring the Pathogenic Role and Therapeutic Implications of Interleukin 2 in Autoimmune Hepatitis

“…The prospect of highly specific Treg stimulation of long duration advances the prospect of ultra-low-dose IL-2 in autoimmune hepatitis. This prospect has also been improved by the development of a slow release, long acting, liposomal preparation of recombinant IL-2 for consideration in the treatment of neoplastic disease [277]. Similar IL-2 preparations that could be designed to deliver a continuous low dose of recombinant IL-2 in autoimmune disease may be possible.…”

“…The precedents established in animal models and preliminary clinical trials support further investigation of lowdose recombinant IL-2 therapy in autoimmune hepatitis, and investigations that are actively evaluating methods to improve Treg targeting and patient tolerance by engineering molecules of IL-2 that have sustained action and preferred Treg binding [274][275][276]278] or delivery systems that allow slow continuous release [277] strengthen these prospects.…”

Interleukin-2: Evaluation of Routes of Administration and Current Delivery Systems in Cancer Therapy

“…The first category aimed at increasing IL‐2 therapeutic outcome through extending its half‐life. This category includes but not restricted to gene therapy,121, 122 liposomes,123, 124 polymeric microspheres,64, 125 thermo responsive synthetic polymers,126 hydrogels,127 and biodegradable elastomeric devices 128. It is important to state here that the above used references are only representative citations for research work conducted on those IL‐2 delivery systems and do not constitute a comprehensive list of all the work done in that area.…”

Liposome-targeted delivery for highly potent drugs

“…As already mentioned elsewhere passive targeting besides pegylation of liposomal protein and peptide are prevalent and well-worked structures to overcome their instability and short half-life (Deshpande et al 2013, Milla et al 2012 liposomal IL-2 resulted in better distribution, enhanced the duration time in the systemic circulation and improved therapeutic effect against tumor after subcutaneous administration to mice (Kanaoka et al 2003).…”