Lipoprotein-mimicking biovectorized systems for methotrexate delivery

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Drug Delivery Systems

Background:

• Lipid nanoparticles (LNPs) are crucial for drug delivery.
• Developing biomimetic systems enhances in vivo performance.
• Methotrexate delivery faces challenges in targeting and controlled release.

Purpose of the Study:

• To develop and characterize novel lipoprotein-mimicking biovectorized systems (LMBVs) for methotrexate delivery.
• To optimize LMBV composition and preparation for enhanced drug delivery.
• To evaluate the in vivo behavior and therapeutic potential of LMBVs.

Main Methods:

• LMBVs were prepared using a microemulsion congealing technique.
• Palmitoylpolyethylene glycol 4000 (p-PEG 4000) was anchored as an apoprotein analogue.
• Formulations were characterized for size, zeta potential, entrapment, anchoring efficiency, release kinetics, pharmacokinetics, and tissue distribution.

Main Results:

• LMBVs exhibited a size of 70-76 nm with low polydispersity (0.09-0.18).
• Zeta potential changed from -63.2 to -19.3 after p-PEG 4000 coating.
• Drug entrapment efficiency ranged from 22.6% to 30.2%, with 74.0% anchoring efficiency.
• Zero-order drug release was observed, with enhanced circulation half-life and prolonged tissue accumulation.

Conclusions:

• LMBVs, biomimetic of lipoproteins, demonstrate promising characteristics for drug delivery.
• The p-PEG 4000 coating enhances in vivo behavior, similar to natural lipoproteins.
• LMBVs offer potential for targeted delivery and controlled systemic release of methotrexate for cancer therapy.