ArticleJournal of controlled release : official journal of the Controlled Release Society2013
PEGylation of interferon α2 improves lymphatic exposure after subcutaneous and intravenous administration and improves antitumour efficacy against lymphatic breast cancer metastases.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Population Pharmacokinetic Model of Pegbing in Healthy Subjects and Chronic Hepatitis B Patients.CPT: pharmacometrics & systems pharmacology · 2025Trial
- Classification system proposed to guide the design, development, regulatory approval, and scaling of long acting, small- and macro-molecule parenteral products (CS-BLAP).Journal of pharmaceutical sciences · 2026Review
- Leveraging Lymphatic System Targeting in Systemic Lupus Erythematosus for Improved Clinical Outcomes.Pharmacological reviews · 2024Review
- Using Graph-Based Signatures to Guide Rational Antibody Engineering.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Type of anesthesia for cancer resection surgery: No differential impact on cancer recurrence in mouse models of breast cancer.PloS one · 2023Article
- Investigating the stabilisation of IFN-α2a by replica exchange molecular dynamics simulation.Journal of molecular modeling · 2022Article
- Disrupting circadian rhythms promotes cancer-induced inflammation in mice.Brain, behavior, & immunity - health · 2022Article
- Near-infrared upconversion multimodal nanoparticles for targeted radionuclide therapy of breast cancer lymphatic metastases.Frontiers in immunology · 2022Article
- Fibroblast Growth Factor 2 Conjugated with Monomethyl Auristatin E Inhibits Tumor Growth in a Mouse Model.Biomacromolecules · 2021Article
- Spontaneous regression of micro-metastases following primary tumor excision: a critical role for primary tumor secretome.BMC biology · 2020Article
- Cetuximab Exhibits Sex Differences in Lymphatic Exposure after Intravenous Administration in Rats in the Absence of Differences in Plasma Exposure.Pharmaceutical research · 2020Article
- Understanding Inter-Individual Variability in Monoclonal Antibody Disposition.Antibodies (Basel, Switzerland) · 2019Review
- Probing the subcutaneous absorption of a PEGylated FUD peptide nanomedicine via in vivo fluorescence imaging.Nano convergence · 2019Article
- Lymphatic Transport and Lymph Node Location of Microspheres Subcutaneously Injected in the Vicinity of Tumors in a Rabbit Model of Breast Cancer.Pharmaceutical research · 2018Article
- Article
- Addition of 20-kDa PEG to Insulin Lispro Alters Absorption and Decreases Clearance in Animals.Pharmaceutical research · 2016Article
- The lymphatic system and pancreatic cancer.Cancer letters · 2016Review
- Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination.Nature communications · 2016Article
- β2-adrenoceptor signaling regulates invadopodia formation to enhance tumor cell invasion.Breast cancer research : BCR · 2015Article
- From sewer to saviour - targeting the lymphatic system to promote drug exposure and activity.Nature reviews. Drug discovery · 2015Review
Corrections and comments
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Authors and funding
7 authors.
Funding
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, 19kDa) and PEGylated interferon α2b (IFN-PEG12, 31kDa) or α2a (IFN-PEG40, 60kDa) 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 SC or IV administration (≤1%). In contrast, IFN-PEG12 was efficiently absorbed from the SC injection site (Fabs 82%) and approximately 20% and 8% of the injected dose was recovered in thoracic lymph over 30h after SC or IV administration respectively. IFN-PEG40, however, was incompletely absorbed from the SC injection site (Fabs 23%) and showed similar lymphatic access after SC administration to IFN-PEG12 (21%). The recovery of IFN-PEG40 in thoracic lymph after IV administration, however, was significantly greater (29%) when compared to IV IFN-PEG12. The anti-tumour efficacy of interferon against axillary metastases of a highly lymph-metastatic variant of human breast MDA-MB-231 carcinoma was significantly increased by SC administration of lymph-targeted IFN-PEG12 when compared to the administration of IFN on the ipsilateral side to the axillary metastasis. Optimal PEGylation may therefore represent a viable approach to improving the lymphatic disposition and efficacy of therapeutic proteins against lymphatic diseases.
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