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Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles
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Relationship between Phase Transition and Drug Release of Doxorubicin-Encapsulated Liposomes with Different Lipid
Ryouya Yamada1, Takumi Sato1, Kazuki Haneishi1
1Department of Molecular Pharmaceutics, Meiji Pharmaceutical University.
Biological & Pharmaceutical Bulletin
|November 3, 2025
Summary
Raman spectroscopy offers a new quality assessment method for liposomes, enabling real-time monitoring of drug inclusion and release rates. This technique effectively evaluates liposome phase transitions and drug release properties, particularly in relation to cholesterol content.
Area of Science:
- Pharmaceutical Sciences
- Analytical Chemistry
- Biotechnology
Background:
- Liposomes, complex drug delivery systems, present challenges in quality evaluation due to their intricate structure.
- Conventional quality control methods for liposomes can be diverse and complex.
- Raman spectroscopy is emerging as a Process Analytical Technology (PAT) for pharmaceutical manufacturing, with potential applications in complex drug formulations.
Purpose of the Study:
- To evaluate the phase transition and drug release properties of drug-encapsulated liposomes using Raman spectroscopy.
- To demonstrate the utility of Raman spectroscopy as a novel quality assessment tool for liposomes.
- To investigate the correlation between cholesterol content, liposome phase transition, and drug release.
Main Methods:
- Preparation of drug-encapsulated liposomes with varying cholesterol (CHOL) ratios.
- Real-time monitoring of liposome phase transitions using probe-type Raman spectroscopy.
- Quantification of drug release rates via analysis of drug-derived spectral changes over time.
- Application of partial least squares analysis for spectral data interpretation.
Main Results:
- Raman spectroscopy revealed distinct peak intensities corresponding to phase transitions, with higher intensity in low CHOL ratio systems.
- Drug release was significantly higher in low CHOL ratio liposomes, indicated by a faster decrease in drug-derived spectral peaks.
- High CHOL ratio systems exhibited lower drug release, consistent with a more ordered liquid phase.
Conclusions:
- Raman spectroscopy is a viable method for assessing liposome phase transitions and associated drug release characteristics.
- The study highlights the potential of Raman spectroscopy as a PAT tool for real-time quality control of liposomal drug products.
- Cholesterol content significantly influences liposome phase behavior and drug release kinetics, which can be effectively monitored by Raman spectroscopy.

