Gouveia, VM;
Rizzello, L;
Vidal, B;
Nunes, C;
Poma, A;
Lopez-Vasquez, C;
Scarpa, E;
... Battaglia, G; + view all
(2022)
Targeting Macrophages and Synoviocytes Intracellular Milieu to Augment Anti-Inflammatory Drug Potency.
Advanced Therapeutics
10.1002/adtp.202100167.
(In press).
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Advanced Therapeutics - 2022 - Gouveia - Targeting Macrophages and Synoviocytes Intracellular Milieu to Augment.pdf - Published Version Download (3MB) | Preview |
Abstract
Using a preclinical in vivo model of arthritis and the gold standard disease-modifying anti-rheumatic drug, methotrexate, pH-responsive phosphorylcholine polymersomes, elicit both anti-inflammatory and anti-arthritic therapeutic efficacy, while drastically minimizing off-target toxicity. First, the selective accumulation of polymersomes within synovium of inflamed joints. Second, the polymersomes targeting ability toward activated macrophages and synoviocytes, via scavenger receptors, allow their uptake via endocytosis. And third, the polymersomes pH-responsiveness enables the drug escape from early endosomes and hence its intracellular milieu delivery. On-site augment of methotrexate loaded polymersomes enable the complete abrogation of synovial inflammation and prevent the disease progression and severity. Overall, in vitro and in vivo investigations reveal the potential of polymersomes as a promising nanotherapy for treating arthritic inflammation.
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