Targeting activated macrophages intracellular milieu to augment anti-inflammatory drug potency

We present pH-responsive phosphorylcholine polymersomes ability to target activated macrophages via scavenger receptors, enter them via endocytosis, and escape from early endosomes enabling the intra-cellular drug delivery. Using an arthritis experimental model and the gold standard disease modifying anti-rheumatic drug, methotrexate, we prove that polymersomes augments therapeutic efficacy, while minimizing the off-target effect. First, we demonstrate the selective accumulation of polymersomes within the inflamed synovial tissues and cells, including macrophages. Second, we show the beneficial therapeutic effect of methotrexate loaded polymersomes in preventing both joint inflammation and further damage. Hence, we prove the therapeutic potential of polymersomes in enhancing the complete prevention of arthritis progression, which makes it a promising nanotherapy for arthritis treatment as well as other inflammatory disorders. TeaserWe show that the effective targeting and delivery of drugs to the main inflammation actors, the macrophages, enhances arthritis therapy.