Ratiometric Delivery of Mitoxantrone and Berberine Co-encapsulated Liposomes to Improve Antitumor Efficiency and...

Area of Science:

• Nanotechnology in Medicine
• Drug Delivery Systems
• Cancer Therapeutics

Background:

• Combination therapy is crucial for treating malignancies, but optimal drug ratios are essential for synergistic effects.
• Co-encapsulation carriers are vital for coordinated delivery of multiple drugs to tumor cells.

Purpose of the Study:

• To develop a pegylated liposomal formulation co-encapsulating mitoxantrone (MIT) and berberine (BER) at an optimal ratio (MBL).
• To achieve ratiometric loading and delivery of MIT and BER for enhanced synergistic cancer therapy.
• To evaluate the in vivo performance and therapeutic efficacy of the MBL formulation.

Main Methods:

• Development of a co-encapsulated pegylated liposomal formulation (MBL) of mitoxantrone and berberine.
• Characterization of encapsulation efficiency (EE) and drug loading.
• In vivo evaluation in murine 4T1 breast tumor and L1210 ascitic tumor models after intravenous injection.

Main Results:

• MBL demonstrated high EE and drug loading, enabling ratiometric delivery.
• The formulation extended blood circulation and enhanced tumor accumulation of both drugs.
• MBL maintained the desired drug ratio in tumors for 48 hours, significantly inhibiting tumor growth and reducing cardiac toxicity in the 4T1 model.
• MBL prolonged survival in the L1210 ascitic tumor model.

Conclusions:

• Co-encapsulated liposomes offer a promising strategy for synergistic combination therapy in cancer treatment.
• The MBL formulation improves drug delivery, enhances therapeutic efficacy, and reduces toxicity compared to single-drug liposomes.
• This approach holds potential for improving clinical applications against various cancers.