Abstract
Abdominal aortic aneurysm (AAA) is a life-threatening disease. However, no systemically injectable drug has been approved for AAA treatment due to low bioavailability. Polymeric micelles are nanomedicines that have the potential to improve therapeutic efficacy by selectively delivering drugs into disease sites, and research has mainly focused on cancer treatments. Here, we developed a statin-loaded polymeric micelle to treat AAAs in rat models. The micelle showed medicinal efficacy by preventing aortic aneurysm expansion in a dose-dependent manner. Furthermore, the micelle-injected group showed decreased macrophage infiltration and decreased matrix metalloproteinase-9 activity in cases of AAA.
Highlights
Abdominal aortic aneurysm (AAA) is a common and lethal disease with a possible risk of rupture
We studied the prevention of AAA expansion using an elastase-induced rat experimental AAA model to determine its potential as an injectable nanomedicine for vascular disease-targeted drug delivery
Poly(ethylene glycol)-b-poly(l-lysine) (PEG-PLys) and PEG-PLys(FPBA) were synthesized according to our previous research [20,21], and their characteristics were measured by proton nuclear magnetic resonance (1H-NMR) and gel permeation chromatography (Figures S1–S4)
Summary
Abdominal aortic aneurysm (AAA) is a common and lethal disease with a possible risk of rupture. Polymeric micelles form due to the self-assembly of polymer–drug conjugates (amphiphilic polymers) These are well-known as systemically injectable nanomedicines, comprising a dense biocompatible outer shell and a drug-incorporated core. Some preclinical and clinical studies have shown effective therapeutic outcomes using nanomedicines incorporating cisplatin, DACH-platin, and doxorubicin with reduced toxic side effects of the payloads [11,12,13] These studies have mainly involved cancer therapies, there are few challenges in vascular diseases, especially toward AAA treatment. Some previous reports described that statins are currently one of the candidate drugs with favorable clinical data for reducing AAA growth, mortality, and rupture rates [17], but others claimed less impact for aneurysm growth in humans [18] These trials were done using statin tablet, i.e., oral administration. We studied the prevention of AAA expansion using an elastase-induced rat experimental AAA model to determine its potential as an injectable nanomedicine for vascular disease-targeted drug delivery
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