Analyzing Liposomal Drug Delivery Systems in Three-Dimensional Cell Culture Models Using MALDI Imaging Mass...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Cancer chemotherapeutics face challenges in reaching all diseased cells.
• Novel drug delivery systems, such as liposomes, are being investigated to improve drug targeting and efficacy.
• Liposomes offer low toxicity, high biocompatibility, and the capacity to transport substantial drug payloads to tumor sites.

Purpose of the Study:

• To evaluate the penetration of doxorubicin-encased liposomes into three-dimensional (3D) cell cultures (spheroids).
• To compare the distribution of liposomal doxorubicin versus free doxorubicin within spheroids.
• To investigate the capability of Matrix-Assisted Laser Desorption/Ionization-Imaging Mass Spectrometry (MALDI-IMS) in analyzing drug penetration and metabolism within 3D models.

Main Methods:

• Liposomes composed of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cholesterol were prepared via extrusion.
• Doxorubicin was encapsulated within the hydrophilic core of the liposomes.
• Spheroids were treated with liposomal doxorubicin, free doxorubicin, or media control, and drug distribution was analyzed over 72 hours using MALDI-IMS and fluorescence microscopy.

Main Results:

• MALDI-IMS successfully visualized the penetration of both free and liposomal doxorubicin throughout the spheroids within 12 hours.
• The study demonstrated that liposomal doxorubicin actively releases its payload within the spheroid.
• MALDI-IMS detected three doxorubicin metabolites, indicating cellular metabolism of the drug during treatment, a capability not offered by fluorescence microscopy.

Conclusions:

• MALDI-IMS is a powerful tool for analyzing the penetration and distribution of liposomal drug carriers in 3D cell cultures.
• This study provides the first report using MALDI-IMS to assess liposomal drug penetration and drug metabolism in a 3D spheroid model.
• The findings highlight the potential of liposomes as effective drug delivery systems for cancer chemotherapy and underscore the utility of advanced imaging techniques in drug development.