The DOI matches its Crossref record; 38 of the 39 references it cites were found in a registry or an index.
5-Aminolevulinic acid and its derivatives: physical chemical properties and protoporphyrin IX formation in cultured cells
Open accessAbstract
Protoporphyrin IX (PpIX) is used as a fluorescence marker and photosensitizing agent in photodynamic therapy (PDT). A temporary increase of PpIX in tissues can be obtained by administration of 5-aminolevulinic acid (ALA). Lipophilicity is one of the key parameters defining the bioavailability of a topically applied drug. In the present work, octanol-water partition coefficients of ALA and several of its esters have been determined to obtain a parameter related to their lipophilicity. The influence of parameters such as lipophilicity, concentration, time, and pH value on PpIX formation induced by ALA and its esters is then investigated in human cell lines originating from the lung and bladder. ALA esters are found to be more lipophilic than the free acid. The optimal concentration (c(opt), precursor concentration at which maximal PpIX accumulation is observed) is then measured for each precursor. Long-chained ALA esters are found to decrease the c(opt) value by up to two orders of magnitude as compared to ALA. The reduction of PpIX formation observed at higher concentrations than c(opt) is correlated to reduced cell viability as determined by measuring the mitochondrial activity. Under optimal conditions, the PpIX formation rate induced by the longer-chained esters is higher than that of ALA or the shorter-chained esters. A biphasic pH dependence on PpIX generation is observed for ALA and its derivatives. Maximal PpIX formation is measured under physiological conditions (pH 7.0-7.6), indicating that further enhancement of intracellular PpIX content may be achieved by adjusting the pharmaceutical formulation of ALA or its derivatives to these pH levels.
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“Since topically applied ALA has slow and limited tissue penetration due to its hydrophilicity, hexaminolevulinate (HAL) with increased lipophilicity was developed to overcome these limitations [59].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [59]
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Metadata
- Authors
- Uehlinger, P., Zellweger, M., Wagnières, G., Juillerat-Jeanneret, L., van den Bergh, H., & Lange, N.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Venue
- Journal of Photochemistry and Photobiology B: Biology
- Publisher
- Elsevier BV
- Published
- 2000-01
- Volume
- 54
- Issue
- 1
- Pages
- 72-80
- ISSN
- 1011-1344 (ISSN-L)
- OpenAlex
- W1996290414
- Cited by
- 221
- References
- 39
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 2 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 5 · 2015: 4 · 2014: 7 · 2013: 7 · 2012: 11
- FWCI
- 12.40
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Locations
- Journal of Photochemistry and Photobiology B Biology (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Photodynamic Therapy Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Physical Sciences › Materials Science › Materials Chemistry › Porphyrin and Phthalocyanine Chemistry
- Keywords
- 5-aminolevulinic acid, protoporphyrin IX, photodynamic therapy, photosensitizers, lipophilicity, octanol-water partition coefficient, pH dependence, cell viability, lung cancer cell lines, bladder cancer cell lines, mitochondrial activity
- MeSH terms
- Aminolevulinic Acid, Urinary Bladder Neoplasms, Bronchi, Cell Line, Humans, Hydrogen-Ion Concentration, Kinetics, Lung Neoplasms, Protoporphyrins, Structure-Activity Relationship, Tumor Cells, Cultured, Photosensitizing Agents, Respiratory Mucosa
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