Lipid nanocarriers for promoting angiogenesis

This invention describes a new way to deliver a protein called transmembrane stem cell factor (tmSCF) using tiny carriers made of lipids (fats). This helps promote the growth of new blood vessels and could treat peripheral vascular disease.

Background

Peripheral vascular disease (PVD) affects a significant portion of the aging population, often leading to critical limb ischemia and amputation. Existing treatments, such as stenting or bypass surgery, are invasive and prone to compli­cations, particularly in cases of diffuse vascular disease. Therapeutic angiogenesis, focusing on stimulating new blood vessel growth, offers a promising alternative.

Current approaches to therapeutic angiogenesis using growth factors like FGF‑2, VEGF, or PDGF-BB have limitations, particularly in patients with com­promised vascular growth. While soluble stem cell factor (SCF) has shown potential, its clinical application is hampered by hyperreactivity responses in some individuals. Additionally, delivering therapeutic agents effectively to ischemic tissues while avoiding systemic side effects remains a challenge.

Technology description

This technology involves the use of lipid vesicles, specifically proteoliposomes or nanodiscs, as carriers for trans­membrane stem cell factor (tmSCF) to promote angiogenesis and treat peripheral vascular disease (PVD). These vesicles, composed of phospholipids like DOPC, DOPE, sphingomyelin, and cholesterol, mimic cell membranes, enhancing tmSCF stability and activity. This delivery system facilitates tmSCF’s interaction with endothelial cells, stimulating their proliferation and tube formation, thereby aiding in the revascularization of ischemic tissues.

The technology is differentiated by its use of tmSCF, a membrane-linked form of stem cell factor, which has not been previously utilized as a therapeutic protein due to production and solubility challenges. Encapsulating tmSCF within lipid vesicles overcomes these limitations and allows for targeted delivery, enhancing its therapeutic efficacy.

This approach offers a less invasive alternative to traditional PVD treatments like stenting or bypass surgery. Furthermore, unlike soluble SCF, the tmSCF lipid carriers do not exhibit hyperreactivity, minimizing potential adverse effects.

Benefits

• Less invasive alternative to traditional treatments for PVD (e.g., stenting or bypass surgery)
• Facilitates the growth of new blood vessels
• Can be encapsulated in biodegradable microcapsules or microbeads for controlled release
• Improves activity in models of endothelial proliferation and tube formation
• Improves revascularization in ischemic tissues
• Does not cause hyperreactivity, unlike soluble SCF

Commercial applications

• Peripheral ischemia
• Stroke treatment
• Diabetic ulcers
• Cell expansion
• Myocardial ischemia

Patent link

https://patents.google.com/patent/US20210145931A1/en?oq=+17%2f047%2c135