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Comparation of liposomal formulations of ALA Undecanoyl ester for its use in photodynamic therapy

Paper ID Volume ID Publish Year Pages File Format Full-Text
30353 44471 2009 7 PDF Available
Title
Comparation of liposomal formulations of ALA Undecanoyl ester for its use in photodynamic therapy
Abstract

ALA administration has been used to induce the endogenous photosensitiser Protoporphyrin IX for photodynamic therapy (PDT) of tumours. However, the hydrophilic nature of ALA limits its ability to penetrate through skin restricting the use of ALA-PDT to superficial diseases. Lipophilic derivatives of ALA such as ALA Undecanoyl ester (Und-ALA) were designed to have better diffusing properties. However, Und-ALA, applied topically on the skin over the tumour, induced low porphyrin content. To improve Und-ALA efficacy we tested the efficacy of Und-ALA as porphyrin inducer, delivered in phosphatidylcholine and phosphatidylglycerol (PC–PG) or phosphatidylcholine and phosphatidic acid (PC–PA) liposomal formulations.Entrapment of Und-ALA into PC–PA or PC–PG liposomes resulted in a dramatic impairment of toxicity in the mammary tumour LM3 cells. However, liposomal Und-ALA induced lower intracellular porphyrin content compared to free ALA, although total porphyrins content (intracellular + media) from free Und-ALA resulted equal compared to liposomal Und-ALA, due to induction of porphyrins release induced by the latter.Topical administration of Und-ALA in PC–PG or PC–PA liposomes over the skin of LM3 subcutaneously injected mice, induced equal amount of tumour porphyrins as compared to free Und-ALA.The kinetics of porphyrins synthesis from Und-ALA is similar for free and liposomal formulations both in vivo and in vitro, showing that release of Und-ALA from liposomes is not gradual and suggesting that liposome membranes either fuses or binds to the cell membranes.To sum up, the incorporation of Und-ALA into liposomes of PC–PA or PC–PG composition does not improve the rate of porphyrin synthesis either in vitro or in vivo, due to a massive release of extracellular porphyrins and a poor cytoplasmatic release of the liposome content. The design of new liposome compositions either favouring endocytosis or coated with natural polymers to prevent Und-ALA interaction with cellular membrane are desired to overcome intracellular porphyrin release after long-chained ALA esters treatment.

Keywords
ALA, 5-aminolevulinic acid; FU, fluorescence units; He-ALA, ALA-Hexyl ester; MTT, (3-[45-dimethylthiazol-2-yl]-25-diphenyltetrazoliumbromide); PC, phosphatidylcholine; PA, phosphatidic acid; PG, phosphatidylglycerol; PDT, photodynamic therapy; PpIX, proto
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Comparation of liposomal formulations of ALA Undecanoyl ester for its use in photodynamic therapy
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 96, Issue 2, 3 August 2009, Pages 152–158
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us