Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Nanotechnology

Background:

• 3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is a potent anti-proliferative analog of curcumin.
• Poor aqueous solubility of EF24 limits its parenteral formulation and therapeutic efficacy.
• Development of effective drug delivery systems is crucial for enhancing the bioavailability and activity of poorly soluble drugs like EF24.

Purpose of the Study:

• To develop and characterize a novel liposome formulation of EF24 using a

Main Methods:

• EF24 was complexed with hydroxypropyl-β-cyclodextrin (HPβCD) to enhance its aqueous solubility.
• Liposomes encapsulating the EF24-HPβCD inclusion complex were prepared using dehydration-rehydration and extrusion techniques.
• Liposome size was optimized using freeze-thaw cycles and extrusion.
• Co-encapsulation of glutathione enabled labeling with Technetium-99m (Tc-99m) for imaging.
• Anti-proliferative activity was assessed in H441 and PC-3 cancer cell lines.
• Pharmacokinetics and biodistribution of Tc-99m-labeled EF24 liposomes were evaluated in rats.

Main Results:

• The EF24-HPβCD inclusion complex significantly increased EF24 aqueous solubility from 1.64 to 13.8 mg/mL.
• Liposomes with an average size of 177 ± 6.5 nm were successfully prepared with high encapsulation efficiency.
• Liposomal EF24 exhibited superior anti-proliferative activity compared to free EF24 at 10 microM in vitro.
• Tc-99m-labeled EF24 liposomes showed biphasic clearance from rat blood with a long terminal half-life.
• Biodistribution studies indicated significant uptake of the liposomes in the liver and spleen.

Conclusions:

• The "drug-in-CD-in liposome" approach is a feasible and effective strategy for formulating parenteral preparations of EF24.
• Liposomal EF24 demonstrates enhanced anti-proliferative efficacy and offers potential for targeted delivery and imaging.
• This formulation strategy holds promise for improving the therapeutic outcomes of EF24 in cancer treatment.