Int J Med Sci 2016; 13(7):483-489. doi:10.7150/ijms.15411 This issue

Research Paper

A Formulation Study of 5-Aminolevulinic Encapsulated in DPPC Liposomes in Melanoma Treatment

Ming-Wei Lin1, Yaw-Bin Huang1, 2, Chun-Lin Chen1,3, Pao-Chu Wu2, Chien-Ying Chou2, Ping-Ching Wu4,5,6✉, Shih-Ya Hung7, 8,✉

1. Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 80756, Taiwan
2. School of Pharmacy, Kaohsiung Medical University, Kaohsiung 80756, Taiwan
3. Department of Biological Science, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
4. Department of Biomedical Engineering, National Cheng Kung University, Tainan, 701, Taiwan
5. Institute of Oral Medicine and Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University Tainan 701, Taiwan
6. Medical Device Innovation Center, Taiwan Innovation Center of Medical Devices and Technology, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 701, Taiwan
7. Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
8. Division of Colorectal Surgery, China Medical University Hospital, Taichung 40447, Taiwan

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Lin MW, Huang YB, Chen CL, Wu PC, Chou CY, Wu PC, Hung SY. A Formulation Study of 5-Aminolevulinic Encapsulated in DPPC Liposomes in Melanoma Treatment. Int J Med Sci 2016; 13(7):483-489. doi:10.7150/ijms.15411. Available from

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Photodynamic therapy (PDT) is a widely used technique for epithelial skin cancer treatment. 5-aminolevulinic acid (5-ALA) is a drug currently used for PDT and is a hydrophilic molecule at its physiological pH, and this limits its capacity to cross the stratum corneum of skin. Since skin penetration is a key factor in the efficacy of topical 5-ALA-mediated PDT, numerous strategies have been proposed to improve skin penetration. Yet this problem is still ongoing. The results of a previous study showed a low rate of 5-ALA encapsulated in liposomes (5.7%) that were 400 nm in size. In the present study, we used 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes as vehicles and tested their delivery efficacy of 5-ALA-medicated PDT both in vitro and in vivo. Our data shows that 5-ALA encapsulated in 0.1 or 0.5% DPPC liposomes (5-ALA/DPPC) had a better encapsulated rate (15~16%) and were smaller in size (84~89 nm). We found the 5-ALA/DPPC formulation reduced cell viability, mitochondria membrane potential, and enhanced intracellular ROS accumulation as compared to 5-ALA alone in melanoma cells. Furthermore, the 5-ALA/DPPC formulation also had better skin penetration ability as compared to the 5-ALA in our ex vivo data by assaying 5-ALA converted into protoporphyrin IX (PpIX) in the skin of the mice that were experimented on. In melanoma xenograft models, 5-ALA/DPPC enhanced PpIX accumulation only in tumor tissue but not normal skin. In conclusion, we found DPPC liposomes to be good carriers for 5-ALA delivery and believe that they may prove useful in 5-ALA-mediated PDT in the future.

Keywords: 5-aminolevulinic acid, DPPC liposomes, melanoma, photodynamic therapy, skin cancer