| 1. |
- Bender, Johanna, 1975, et al.
(författare)
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Lipid cubic phases for improved topical drug delivery in photodynamic therapy.
- 2005
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 106:3, s. 350-360
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Tidskriftsartikel (refereegranskat)abstract
- We have evaluated the efficacy of lipid cubic phases, highly ordered self-assembly systems on the nanometer level, as drug delivery vehicles for in vivo topical administration of delta-aminolevulinic acid (ALA) and its methyl ester (m-ALA) on nude mice skin. ALA, a precursor of heme, induces the production of the photosensitizer protoporphyrin IX (PpIX) in living tissue. Measuring the PpIX fluorescence at the skin surface, after topical administration, makes indirect quantification of the penetration of ALA into the tissue possible. Cubic phases were formed of lipid (monoolein or phytantriol), water and drug. In some cases, propylene glycol was included in the cubic phase as well. The drug concentration was 3% (w/w, based on the total sample weight) in all investigated vehicles. When the formulations were applied for 1 h, the monoolein cubic systems and the three-component phytantriol sample showed higher fluorescence compared to the standard ointment during the 10 h of measurement. Both ALA and m-ALA yielded similar results, although the differences between the investigated vehicles were more pronounced when using m-ALA. For the 24-h applications, the monoolein cubic systems with m-ALA showed faster PpIX formation than the standard ointment, implying higher PpIX levels at short application times (less than 4 h). The systemic PpIX fluorescence of ALA was elevated by using the lipid cubic formulations. Notably, a small systemic effect was also observed for the monoolein cubic sample with m-ALA. These results imply improved PpIX formation when using the lipid cubic systems, most probably due to enhanced drug penetration.
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| 2. |
- Bender, Johanna, 1975, et al.
(författare)
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Lipid cubic phases in topical drug delivery: Visualization of skin distribution using two-photon microscopy
- 2008
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 129:3, s. 163-169
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Tidskriftsartikel (refereegranskat)abstract
- The distribution of sulphorhodamine B (SRB), a fluorescent hydrophilic model drug, was investigated in human skin after passive diffusion using four different topical delivery systems. The delivery vehicles applied were two bicontinuous lipid cubic systems, a commercial ointment and water. The lipid cubic systems consisted of either monoolein (MO) or phytantriol (PT) and water. The formulations were applied on full-thickness human skin during 24 h. Thereafter the samples were investigated using two-photon microscopy (TPM). The TPM system consisted of an inverted microscope with a 40× water-immersion objective, laser scan-box, and a pulsed femtosecond titanium:sapphire laser operating at 780 nm. The fluorescence was detected using a 560 nm long-pass filter. Sequential optical sectioning was performed, resulting in images obtained at different tissue depths. TPM revealed that SRB mainly penetrates the skin via the intercellular lipid matrix. Samples exposed to the cubic phases showed a higher accumulation of SRB in micro-fissures, from which a fluorescent network of threadlike structures spread laterally in the tissue. These structures were also detected in some of the ointment samples, but not as frequent. The penetration of SRB into the stratum granulosum was deduced from the fluorescence of SRB present inside polygonal keratinocytes with cell nuclei. Higher SRB fluorescence was obtained in the outermost layer of the epidermis using the bicontinuous cubic phases, compared to when using the reference formulations. Thus, our results suggest that the dominating delivery route using the cubic phases is via micro-fissures caused by microscopic clustering of the keratinocytes in the skin. From these micro--fissures hydrophilic compounds, here modeled by SRB, can diffuse into the surrounding intercellular lipid matrix acting like a source for sustained release.
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| 3. |
- Ericson, Marica B, 1974, et al.
(författare)
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Bispectral fluorescence imaging combined with texture analysis and linear discrimination for correlation with histopathologic extent of basal cell carcinoma
- 2005
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Ingår i: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668 .- 1560-2281. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescence imaging has been shown to be a potential complement to visual inspection for demarcation of basal cell carcinoma (BCC), which is the most common type of skin cancer. Earlier studies have shown promising results when combining autofluorescence with protoporphyrin IX (Pp IX) fluorescence, induced by application of delta-5-aminolaevulinic acid (ALA). In this work, we have tried to further improve the ability of this technique to discriminate between areas of tumor and normal skin by implementing texture analysis and Fisher linear discrimination (FLD) on bispectral fluorescence data of BCCs located on the face. Classification maps of the lesions have been obtained from histopathologic mapping of the excised tumors. The contrast feature obtained from co-occurrence matrices was found to provide useful information, particularly for the ALA-induced Pp IX fluorescence data. Moreover, the neighborhood average features of both autofluorescence and Pp IX fluorescence were preferentially included in the analysis. The algorithm was trained by using a training set of images with good agreement with histopathology, which improved the discriminability of the validation set. In addition, cross validation of the training set showed good discriminability. Our results imply that FLD and texture analysis are preferential for correlation between bispectral fluorescence images and the histopathologic extension of the tumors.
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| 4. |
- Ericson, Marica B, 1974
(författare)
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Deep tissue imaging of cell structure
- 2007
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Ingår i: SPIE newsroom. ; doi: 10.1117/2.1200709.0871
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Two-photon fluorescence microscopy can be used for non-invasive skin cancer diagnostics and topical drug delivery investigations.
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| 5. |
- Ericson, Marica B, 1974, et al.
(författare)
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Review of photodynamic therapy in actinic keratosis and basal cell carcinoma
- 2008
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Ingår i: Therapeutics and Clinical Risk Management. - 1178-203X. ; 4:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- The number of non-melanoma skin cancers is increasing worldwide, and so also the demand for effective treatment modalities. Topical photodynamic therapy (PDT) using aminolaevulinic acid or its methyl ester has recently become good treatment options for actinic keratosis and basal cell carcinoma; especielly when treating large areas and areas with field cancerization. The cure rates are usually good, and the cosmetic outcomes excellent. The only major side effect reported is the pain experienced by the patients during treatment. This review covers the fundamental aspects of topical PDT and its application for treatment of actinic keratosis and basal cell carcinoma. Both potentials and limitations will be reviewed, as well as some recent development within the field.
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| 6. |
- Ericson, Marica B, 1974, et al.
(författare)
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Two-photon laser-scanning fluorescence microscopy applied for studies of human skin
- 2008
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Ingår i: Journal of Biophotonics. - : Wiley. - 1864-0648 .- 1864-063X. ; 1:4, s. 320-330
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Tidskriftsartikel (refereegranskat)abstract
- Two-photon laser scanning fluorescence microscopy (TPM) has been shown to be advantageous for imaging optically turbid media such as human skin. The ability of performing three-dimensional imaging without presectioning of the samples makes the technique not only suitable for noninvasive diagnostics but also for studies of topical delivery of xenobiotics. Here, TPM is used as a method to visualize both autofluorescent and exogenous fluorophores in skin. Samples exposed to sulforhodamine B have been scanned from two directions to investigate attenuation effects. It is shown that optical effects play a major role. Thus, TPM is excellent for visualizing the localization and distribution of fluorophores in human skin, although quantification might be difficult. Furthermore, an image-analysis algorithm has been implemented to facilitate interpretation of TPM images of autofluorescent features of nonmelanoma skin cancer obtained ex vivo. The algorithm was designed to detect cell nuclei and currently has a sensitivity and specificity of 82% and 78% to single cell nuclei. However, in order to detect multinucleated cells, the algorithm needs further development. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
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| 7. |
- Ericson, Marica B, 1974, et al.
(författare)
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Two-photon microscopy of non-melanoma skin cancer: initial experience and diagnostic criteria ex vivo
- 2007
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Ingår i: Proc. SPIE. - : SPIE. ; 6630
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Konferensbidrag (refereegranskat)abstract
- Multiphoton microscopy is an interesting optical technique, which allows for non-invasive imaging of highly light scattering media such as human skin. Recent reports have showed the potential of applying this technique for 3D visualisation of cell structures of biological tissue without previous sectioning of the tissue samples. In this study, we have applied two-photon microscopy on excised lesions of human non-melanoma skin cancer ex vivo in order to find diagnostic criteria using this technique. The skin samples have been investigated by a multiphoton microscopy system based on a fs-pulsed Ti:sapphire laser connected to a confocal microscope. The autofluorescence of the skin was detected using excitation at 780 nm. The cell nuclei distribution turned out to be one important parameter, which can be used for discriminating between tumour and normal tissue. We are now developing a technique for automatic detection and characterisation of tissue, based on an image analysis algorithm. The detection of cell nuclei has been found crucial for this purpose. The goal is to develop a fast characterisation algorithm that can be used on line in connection to in vivo investigations. This would allow for a true non-invasive biopsy technique in the future.
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| 8. |
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| 9. |
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| 10. |
- Hörfelt, Camilla, 1970, et al.
(författare)
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Single Low-dose Red Light is as Efficacious as Methyl-aminolevulinate-Photodynamic Therapy for Treatment of Acne: Clinical Assessment and Fluorescence Monitoring
- 2009
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555. ; 89:4, s. 372-378
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Tidskriftsartikel (refereegranskat)abstract
- This controlled study investigated single low-dose red light photodynamic therapy and methyl-aminolevulinate (MAL) for treatment of moderate to severe facial acne in 19 patients. The right cheek was treated with MAL (160 mg/g) for 3 h prior to illumination. The left cheek received red light only. Both cheeks were illuminated with narrow-band red light (635 nm) at a light dose of 15 J/cm(2). The global severity of acne was assessed at baseline and at follow-up, 10 and 20 weeks after treatment. Fluorescence images, clinical photographs and skin surface biopsies were obtained. Both MAL-photodynamic therapy and control areas showed a significant decrease in acne score at follow-up; no significant difference was found compared with control. MAL-photodynamic therapy was associated with adverse effects such as erythema and stinging. Fluorescence images revealed poor selectivity of MAL-induced fluorescence to the acne lesions, suggesting a general photoablating mechanism rather than selective destruction of sebaceous glands. No significant reduction in Propionibacterium acnes or sebum excretion was found.
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