This invention is a proteolipid nanoparticle platform functionalized with apolipoprotein B-100 for localized delivery of therapeutic compounds to atherosclerotic plaques, termed aposomes. Apolipoprotein B-100 is a crucial functional and structural component of low density lipoproteins (LDLs) and therefore plays a critical role in cholesterol transport and atherosclerosis pathophysiology, making it an attractive candidate for targeted drug delivery to atherosclerotic plaques. The aposome platform described herein incorporates plasma derived apolipoprotein B onto the surface of liposomes, allowing them to maintain the key physiological characteristics of LDL while also allowing for the ability to encapsulate drugs or other therapeutic compounds for targeted drug delivery.
Stage of Development
In vitro data: The aposome synthesis protocol has been optimized. Internalization studies and encapsulation efficiency studies revealed that aposomes maintained the key characteristics of native LDL and the encapsulation properties of liposomes.
In vivo data: Atherosclerotic mouse models indicated that aposomes showed a 7-fold increase in plaque accumulation when compared to regular liposomes. Notably, these studies revealed that aposomes accumulated more avidly in small plaques compared to large plaques, providing some evidence that the current platform would be most effective in early stages of atherosclerosis.
Competitive Landscape
The primary pharmacologic treatment strategy for atherosclerosis includes the use of lipid lowering agents and/or anti-inflammatories. Despite the broad availability of these therapies, a large portion of the patient population still presents with complications due to acute thrombotic events. To address the current discrepancies in the efficacy of atherosclerosis treatment and prevention, new solutions need to be formulated for more efficient treatment of this disease. To date, LDL-like particles made for drug delivery have seen limited applications due to significant limitations in manufacturability and scalability. The aposome platform addresses these limitations by utilizing a novel synthesis approach which increases the fabrication time by 72-fold.
Competitive Advantages
• Increased accumulation in atherosclerotic plaques
• Consistent encapsulation efficiency
• Rapid and simple manufacturing and scale-up process
