Journal article
PEGylation of interferon α2 improves lymphatic exposure after subcutaneous and intravenous administration and improves antitumour efficacy against lymphatic breast cancer metastases
LM Kaminskas, DB Ascher, VM McLeod, MJ Herold, CP Le, EK Sloan, CJH Porter
Journal of Controlled Release | Published : 2013
Abstract
The efficacy of protein-based therapeutics with indications in the treatment of lymphatic diseases is expected to be improved by enhancing lymphatic disposition. This study was therefore aimed at examining whether PEGylation can usefully be applied to improve the lymphatic uptake of interferon α2 and whether this ultimately translates into improved therapeutic efficacy against lymph-resident cancer. The lymphatic pharmacokinetics of interferon α2b (IFN, 19 kDa) and PEGylated interferon α2b (IFN-PEG12, 31 kDa) or α2a (IFN-PEG40, 60 kDa) was examined in thoracic lymph duct cannulated rats. IFN was poorly absorbed from the SC injection site (Fabs 36%) and showed little uptake into lymph after S..
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Awarded by National Institutes of Health
Funding Acknowledgements
The authors would like to acknowledge funding support by the Samuel Nissen Charitable Foundation (managed by Perpetual Trustees, Australia). LMK was supported by an NHMRC Career Development fellowship. EKS is supported by a National Breast Cancer Foundation fellowship, NIH CA160890 and NHMRC 1008865. This work was supported in part by infrastructure funding from the Victorian Government Operational Infrastructure Support Scheme to St Vincent's Institute.