title: A Formulation Study of 5-Aminolevulinic Encapsulated in DPPC Liposomes in Melanoma Treatment.
abstract: 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.
authors.affiliation: 1. Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.affiliation: 1. Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 80756, Taiwan; 2. School of Pharmacy, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
authors.forename: Yaw-Bin
authors.initials: YB
authors.lastname: Huang
authors.affiliation: 1. Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 80756, Taiwan; 3. Department of Biological Science, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Chen
authors.affiliation: 2. School of Pharmacy, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
authors.forename: Pao-Chu
authors.initials: PC
authors.lastname: Wu
authors.affiliation: 2. School of Pharmacy, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
authors.forename: Chien-Ying
authors.initials: CY
authors.lastname: Chou
authors.affiliation: 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.
authors.forename: Ping-Ching
authors.initials: PC
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Shih-Ya
authors.initials: SY
authors.lastname: Hung
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D000622:Aminolevulinic Acid / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism
chemical_list: D008081:Liposomes; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D015060:1,2-Dipalmitoylphosphatidylcholine; C081581:colfosceril palmitate; D000622:Aminolevulinic Acid
keywords: 5-aminolevulinic acid; DPPC liposomes; melanoma; photodynamic therapy; skin cancer