Influence of application and formulation factors on the penetration of hypericin in normal mouse skin and UV induced skin tumors

Boiy, Annelies; Roelandts, Rik; Witte, Peter de

doi:10.1016/j.jphotobiol.2007.10.001

Cited by 9 publications

(3 citation statements)

References 25 publications

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“…One of the challenges in the topical administration of photosensitizer is the barrier posed by stratum corneum. Recent studies by Boiy et al 31, 32 investigated the penetration of the photosensitizer hypericin into mouse skin using different vehicles, and reported significant, vehicle‐dependent differences in penetration depths. Based on our own initial findings and their results, we evaluated PDT efficacy in vivo following the topical administration of 50 µl of 0.3 mg ml −1 TMP‐1363 in two vehicles: glycerol/water (2:3) and ethanol/glycerol/water (2:2:1), each applied once for 30 minutes.…”

Section: Resultsmentioning

confidence: 99%

Effective photosensitization and selectivity In Vivo of Candida Albicans by meso‐tetra (N‐methyl‐4‐pyridyl) porphine tetra tosylate

et al. 2011

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Background and Objective The fungus Candida albicans commonly causes mucosal and cutaneous infections in patients with impaired immunity. We investigated the effectiveness of the photosensitizer meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP-1363) in the photodynamic treatment (PDT) of C. albicans infection in vitro and its selectivity in an animal model. Materials and Methods The efficacy of TMP-1363 in PDT of C. albicans in vitro was compared to that of methylene blue (MB) using a colony forming unit (CFU) assay. In vivo infection in the mouse was established by inoculation of C. albicans yeast in the intradermal space of the ear pinna. Two days post-infection, 0.3 mg mL−1 TMP-1363 was administered topically. Thirty minutes after TMP-1363 application, the ears were irradiated at 514 nm using a fluence of 90 J cm−2 delivered at an irradiance of 50 mW cm−2. The ears were excised 2 hours post-irradiation, homogenized and the organism burden was determined by a CFU assay. In vivo wide field and confocal fluorescence imaging assessed the localization of the photosensitizer in relationship to C. albicans. Results Photosensitization with TMP-1363 resulted in a greater than three-log increase in killing of C. albicans in vitro compared to MB. In vivo fluorescence imaging demonstrated a high degree of selective labeling of C. albicans by TMP-1363. PDT of infection using TMP-1363 resulted in a significant reduction in CFU/ear relative to untreated controls. Infected ears subjected to PDT displayed complete healing over time with no observable damage to the pinna. Conclusion Our in vitro and in vivo findings support TMP-1363-mediated PDT as a viable therapeutic approach for the photodynamic treatment of candidiasis.

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Section: Resultsmentioning

confidence: 99%

Effective photosensitization and selectivity In Vivo of Candida Albicans by meso‐tetra (N‐methyl‐4‐pyridyl) porphine tetra tosylate

et al. 2011

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“…Orth et al 10 also reported heterogeneous intratumor distribution of MB following multiple injections of an aqueous vehicle in larger tumor volumes. Methylene blue is water soluble, thus the improved intratumor distribution with the EtOH‐Cremophor injection may be a result of the solvent drag phenomenon, discussed recently by Boiy et al 22 in the context of topical formulations for hypericin. We note also that the injection of 500 µg/ml MB in the Cremophor vehicle resulted in statistically significant EMT6 tumor growth delay relative to untreated controls (Fig.…”

Section: Discussionmentioning

confidence: 98%

Factors influencing tumor response to photodynamic therapy sensitized by intratumor administration of methylene blue

Baran

Giesselman

et al. 2010

Lasers Surg Med

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“…Although potentially promising from its properties (high tumour selectivity and efficiency) and proved in experiments with mice (3)(4)(5), only a few clinical data concerning the treatment of (pre)cancerous lesions of the skin exist. Hypericin was applied successfully on human skin carcinomas BCC (basal cell carcinoma) and SCC (squamous cell carcinoma) (6,7), but an extract of Hypericum perforatum, used in a clinical pilot study on actinic keratoses, BCC and Bowen's disease, showed only partial success (8).…”

Section: Introductionmentioning

confidence: 99%

Time-resolved gene expression profiling of human squamous cell carcinoma cells during the apoptosis process induced by photodynamic treatment with hypericin

Verwanger¹

2009

Int J Oncol

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Abstract. Hypericin is used as a powerful naturally occurring photosensitizer in photodynamic therapy (PDT). Activated by visible light, it kills tumour cells and tissues via generation of reactive oxygen species (ROS). Depending on the protocol, apoptotic cell death can be achieved very effectively by hypericin-PDT. To analyze the fundamental molecular mechanisms leading to apoptosis induced by photodamage especially with regard to human skin cancer cells, we studied the alteration of the gene expression pattern in the human squamous cell carcinoma cell line A-431 at 1.5, 3, 5 and 8 h after hypericin-PDT by cDNA-macroarray technique. Radioactively labelled samples were hybridized onto macroarray filters containing PCR products of 9738 ESTs of the Incyte Human UniGEM Microarray clone set. In total, 168 genes were found to be differentially upregulated and 45 downregulated. Verification of expression changes of 45 genes of interest was performed by quantitative real-time PCR. Due to the observed significant expression changes the following can be concluded: lipoprotein receptor-mediated endocytosis could play a role in the uptake of lipophilic hypericin. Extracellular signal transduction to the cell is reduced, cell detachment facilitated, changes of the morphology, cytoskeleton and formation of apoptotic bodies occur. The promotion of p38 MAPK , ERK, JNK and Ras signalling pathways supports survival and/or apoptosis. Switches between life and death could be the strongly upregulated transcription factors c-jun and FOSB as well as the MAPKphosphatase 1 DUSP-1, possibly activated via H3 histone modifications. ROS activate ER-stress pathways or adaptive response, and provoke damage protection against ROS, partly in a cell-type specific way.

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Influence of application and formulation factors on the penetration of hypericin in normal mouse skin and UV induced skin tumors

Cited by 9 publications

References 25 publications

Effective photosensitization and selectivity In Vivo of Candida Albicans by meso‐tetra (N‐methyl‐4‐pyridyl) porphine tetra tosylate

Effective photosensitization and selectivity In Vivo of Candida Albicans by meso‐tetra (N‐methyl‐4‐pyridyl) porphine tetra tosylate

Factors influencing tumor response to photodynamic therapy sensitized by intratumor administration of methylene blue

Time-resolved gene expression profiling of human squamous cell carcinoma cells during the apoptosis process induced by photodynamic treatment with hypericin

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