Relationship between Phase Transition and Drug Release of Doxorubicin-Encapsulated Liposomes with Different Lipid Compositions Using Raman Spectroscopy

Liposomes have a more complex structure than conventional low-molecular-weight pharmaceuticals, so there is concern that quality evaluation items will be diverse and evaluation methods will be complex. Raman spectroscopy has recently attracted attention as a Process Analytical Technology in the pharmaceutical manufacturing, and its application is expected to expand to biopharmaceuticals and other drugs with complex manufacturing in the future. We have demonstrated that the combination of probe-type Raman spectrometer and partial least squares analysis enables real-time quantification of drug inclusion rate and drug release rate from liposomes, and is useful as a new quality assessment method for liposomes. In this study, we evaluated the phase transition of drug-encapsulated liposomes and the accompanying drug release by using Raman spectroscopy. Drug-encapsulated liposomes were prepared by preparing liposomes with different cholesterol (CHOL) ratios. The phase transition and drug release of liposomes were evaluated by using Raman spectroscopy. Raman spectroscopic measurements showed that the peak intensity of the phase transition was large in systems with low CHOL ratios, while it was low in systems with high CHOL ratios. In the drug release test, a decrease in the peak intensity of the drug-derived spectra over time was observed significantly in the low CHOL ratio system compared to the high CHOL ratio system which is supposed to release drug lower due to liquid-ordered phase, suggesting that the drug release property increased in the low CHOL system. Thus, Raman spectroscopy can be used to evaluate the phase transition and the associated drug release properties of liposomes.