Targeted pH Sensitive Liposomes

NU 2020-170

INVENTORS

• Leo Gordon*
• Dong-Hyun Kim*
• Shuo Yang
• Wooram Park
• Taehoon Sim

SHORT DESCRIPTION

Liposomal nanoparticles composed of pH-sensitive lipids and apolipoprotein that encapsulate andrographolide for lymphoma treatment.

BACKGROUND

Lymphoma, particularly diffuse large B-cell lymphoma (DLBCL), is the most common aggressive type of non-Hodgkin lymphoma with a 10-year survival rate of only 50%. While combination chemotherapy including CHOP (cytoxan, adriamycin, vincristine, prednisolone) regimens are standard treatments, many patients show no improvement or have diverse side effects. Andrographolide, a natural diterpenoid lactone from Andrographis paniculata, shows anti-inflammatory, anti-cancer, and immune-stimulant effects but suffers from poor water solubility, limiting its bioavailability and clinical application.

ABSTRACT

Northwestern researchers have developed liposomal nanoparticles for treating lymphoma. The nanoparticles comprise a lipid bilayer with pH-sensitive lipids, a apolipoprotein A-I coating, and andrographolide encapsulated within. These nanoparticles are stable at physiological pH 7.4 with minimal drug release, but rapidly release contents in acidic environments due to protonation of imidazole groups. The apolipoprotein coating enables scavenger receptor B-1 (SR-B1)-mediated endocytosis specifically into lymphoma cells, triggering intracellular andrographolide delivery in response to the acidic endosomal compartment.

APPLICATIONS

• B- and T-cell lymphoma treatment - targeted therapy for SR-B1-positive lymphoma cells
• Stroke therapy - treats stroke-related damage by modulating local pH microenvironments
• Delivery platform for applications related to antiviral agents or immune modulation

ADVANTAGES

• pH-triggered selective drug release - stable at physiological pH, but releases >50% of payload in acidic microenvironments, minimizing systemic toxicity
• Solubilization of hydrophobic drugs - encapsulates poorly water soluble andrographolide to overcome bioavailability limitations
• Enhanced cellular uptake via SR-B1 targeting - enables specific binding to receptors overexpressed on lymphoma cells to achieve targeted delivery

IP STATUS

• US patent application US20230372532A1 filed