Sulfosalicylate mediates improved vinorelbine loading into LUVs and antineoplastic effects

Area of Science:

• Pharmacology
• Drug Delivery
• Oncology

Background:

• Liposomal formulations can improve drug delivery and therapeutic activity.
• Vinorelbine's lipophilic nature poses challenges for conventional liposomal encapsulation.
• Enhanced drug retention in liposomes is crucial for improved efficacy.

Purpose of the Study:

• To develop a stable liposomal vinorelbine formulation with improved drug retention.
• To evaluate the in vitro and in vivo performance of the novel formulation.
• To assess the enhanced antitumor efficacy of liposomal vinorelbine.

Main Methods:

• Utilized ammonium salts of anionic agents to prepare liposomal vinorelbine.
• Employed 5-sulfosalicylate (5ssa) for stable complex formation and vinorelbine stabilization.
• Assessed in vitro drug release, in vivo circulation half-life, and antitumor efficacy in preclinical cancer models.

Main Results:

• 5-sulfosalicylate (5ssa) vesicles exhibited significantly longer in vitro drug release half-life (~12.49 hours) compared to sulfate vesicles (~0.57 hours).
• The 5ssa formulation showed a 2-fold increase in circulation half-life in mice (~13.01 hours).
• Liposomal vinorelbine demonstrated significantly enhanced antitumor efficacy, being at least 4-fold more active than free vinorelbine in preclinical models.

Conclusions:

• 5-sulfosalicylate effectively stabilizes vinorelbine within liposomes, improving drug retention.
• The developed liposomal vinorelbine formulation offers enhanced therapeutic efficacy and prolonged circulation.
• This 5ssa-based liposomal vinorelbine represents a promising strategy for improved cancer treatment.