Carrier activity of sonicated small liposomes containing melphalan to regional lymph nodes of rats

Area of Science:

• Pharmacokinetics
• Drug Delivery Systems
• Nanotechnology

Background:

• Liposomes are widely investigated as drug delivery vehicles.
• Melphalan (MPL) is a chemotherapeutic agent with limited efficacy due to poor biodistribution.
• Optimizing liposome characteristics is crucial for effective drug delivery.

Purpose of the Study:

• To investigate the tissue distribution of melphalan (MPL) encapsulated in liposomes after subcutaneous injection.
• To compare the effects of liposome size and preparation method on drug distribution in rats.

Main Methods:

• Radiolabeled melphalan (14C-MPL) and phosphatidylcholine (3H) were used to track liposome distribution in rats.
• Two types of liposomes were prepared: large, heterogeneous liposomes (brief sonication) and small, uniform liposomes (prolonged sonication, 34 nm mean diameter).
• Tissue distribution and drug concentration were measured over 24 hours post-subcutaneous injection.

Main Results:

• Subcutaneous injection of small, uniform liposomes resulted in high and sustained concentrations of MPL equivalents in regional lymph nodes.
• Large liposomes prepared by brief sonication largely remained at the injection site.
• Lymph node drug concentrations with large liposomes showed only a slight increase above plasma levels.

Conclusions:

• Liposome size critically influences tissue distribution and lymphatic uptake following subcutaneous administration.
• Small, uniformly sized liposomes enhance melphalan delivery to regional lymph nodes, suggesting potential for targeted cancer therapy.
• Prolonged sonication is a viable method for producing small liposomes with improved pharmacokinetic properties.