Biomedical Engineering – From Theory to Applications

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378 Biomedical Engineering – From Theory to Applications adjustable parameters (e.g., wavelength, intensity, duration, spatial and temporal control) that can be optimized to suit a given application. Photoactivated drug delivery can be used to control the release rate of the active principle from a dosage form (i.e., a carrier system), to activate a drug molecule that is already present at the site of action in an inactive form (e.g., a photosensitizer or a prodrug), or it can combine the two (i.e., photocontrolled drug release and drug activation). While photoactivation of sensitizers is well established, the application of photoactivated carrier systems offers new opportunities, including photoresponsive hydrogels, microcapsules, liposomes, nanoparticles and oligonucleotides (Sortino, 2008). As shown recently by Kishwar et al. (2010), ZnO nanorods proved to be an efficient light system attached to a photosensitizer for intracellular necrosis. Zinc oxide (ZnO) has many advantageous properties like direct band gap of 3.37 eV, large exciton binding energy of 60 eV at room temperature and deep level defects emissions that cover the whole visible range. The UV and green emission part of the white light of ZnO can be used for the activation of photosensitizers in PDT. The family of ZnO nanostructures is the richest known so far and the growth of these nanostructures is facilitated by the self organized growth property of this material. Being a bio-safe and bio-compatible material, ZnO is an attractive candidate for biomedical applications. ZnO nanorods grown on the femto tip were shown to deliver the photosensitizer to breast cancerous cells and cause necrosis within few minutes. Topical pain caused by the conventional PDT method can be reduced by this technique. 5.5 Increased fluorescence for photodiagnosis There is a tremendous need for developing novel non-invasive or minimally invasive diagnostic tools for assessing cell/tissue metabolism and functions, in order to discriminate pathological disturbances in early disease stages. The capability to visualize pathologic tissues as first step before surgical procedure or therapy, may clearly increase treatment efficacy. Intensive research is done to get probes with appropriate fluorescence characteristics (high quantum yield, large Stokes shifts, reduced photolability and great suitability for cells and tissues, i.e., well-balanced amphiphyllic character, low or no intrinsic toxicity, higher excitation wavelengths to prevent spectral interferences due to the auto fluorescence of the biological samples). Due to the adequacy of their properties, the use of porphyrins and metalloporphyrins as near infrared probes (NIR probes) in biomedical applications increased exponentially. Porphyrinic structures, either in solution or in restricted nanometric geometries, typically display long decay times, and this can be used as an extra discrimination advantage for fluorescence imaging (long lifetime probes for lifetime based sensing). We believe that nowadays the analysis of porphyrins and porphyrin-like structures from the point of view of their fluorescence properties is crucial for developing minimally invasive fluorescent tools for diagnosis. Several studies on fluorescent photosensitizers show them as markers and beacons and point toward their dual utility for "seeing and treating" (Chen et al., 2005; Cló et al., 2007). Theranostic nanomedicine, integrating nano-platforms which can diagnose, deliver targeted therapy and monitor response to therapy, is best illustrated in PDT. Photosensitizers will not only kill pathologic cells when light-activated, but being inherently fluorescent they can be used for imaging and locating disease as photosensitizers selectively accumulate within diseased tissue. The use of lasers and minimally invasive fiber optic tools, along with the development of new agents that respond to NIR wavelengths for better tissue penetration, makes direct targeting of deep tissues possible, enabling imaging and treatment of several pathologies. Alongside, nanoprobes have been developed for in vivo optical imaging, which include quantum dots,
Trends in Interdisciplinary Studies Revealing Porphyrinic Compounds Multivalency Towards Biomedical Application up-converting nanophosphors, gold and silica nanoparticles, and photosensitizers containing nanoparticulate carriers. This approach is becoming of increasing interest for oncological applications, addressing the challenges of cancer heterogeneity and adaptability. 5.6 Nano PDT The general advances in medicine and the progress in the use of photosensitizers for PDT directed the research towards the development of photoactive nanoparticles which can be used for cancer therapy, as sensors for tumor indication and imaging and for other applications of PDT such as vascular disorders (Paszko et al., 2011). The effectiveness of PDT could be maximised by using nanoparticles which can improve the photosensitizer solubility in aqueous media, its formulation properties and selectivity to the target tissue. Selectivity improvement can be achieved by nano-formulating the photosensitizers with liposomes or by modifying them using dendrimers, nanotubes (Zhu, 2008) or fullerenes; such liposomal formulation of Foscan (Foslip) is currently under investigation (Buchholz, cited by Lassale et al., 2008). 6. Conclusions Porphyrins have a well-defined place among the substances used in biomedical engineering as medical devices (as defined by the European Council directives No. 93/42/EEC and 98/79/EC, completed by the associated MEDDEV guidance documents) as they can be used effectively as both diagnosis and treatment tools. No Target Drug/Procedure/ Device Theme Status 1. Colorectal Cancer Optical Fluoroscopy Colorectal Cancer Detection by Means of Optical Fluoroscopy 2. Porphyria Cutanea Tarda Exjade Safety and Efficacy of Oral Deferasirox in Patients With Porphyria Cutanea Tarda Safety Study of Aminolevulinic Acid (ALA) to Recruiting 3. Glioma 5-Aminolevuline Acid Enhance Visualization and Resection of Malignant Tumors of the Brain Sputum Labeling Utilizing Synthetic Meso Tetra (4- 4 Lung Cancer CyPath Carboxyphenyl) Porphine (TCPP) for Detection of Lung Cancer Active 5. Acne Vulgaris Visonac Photoactive Porphyrins (PAP) Levels After Topical Visonac Application in Acne Patients PDT with Metvix 160 Photodynamic Therapy (PDT) With Metvix Cream 6. Basal Cell Carcinoma mg/g cream PDT with placebo 160 mg/g Versus PDT With Placebo Cream in Patients With Primary Nodular Basal Cell cream Carcinoma 7. 8. Basal Cell Carcinoma Porphyria PDT with Metvix 160 mg/g cream and Placebo cream Heme arginate; Tin mesoporphyrin PDT With Metvix 160 mg/g Cream Versus PDT With Placebo Cream in Patients With Primary Nodular Basal Call Carcinoma Phase I/II Study of Heme Arginate and Tin Mesoporphyrin for Acute Porphyria Completed 9. Healthy Subjects Eltrombopag; Ciprofloxacin; Placebo Study In Healthy Subjects To Evaluate The Photo- Irritant Potential Of Eltrombopag 10. Basal Cell Carcinoma Procedure: PDT with Metvix PDT in Patients With "High Risk" Basal Cell Metvix 160 mg/g Carcinoma cream 11. Porphyria Heme arginate; Tin mesoporphyrin Studies in Porphyria III: Heme and Tin Mesoporphyrin in Acute Porphyrias Table 5. Current status of medical trials involving porphyrins (source: ClinicalTrials.gov) 379
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BIOMEDICAL ENGINEERING - FROM THEOR
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free online editions of InTech Book
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VI Contents Chapter 9 Targeted Magn
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X Preface stand-alone and readers c
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2 Biomedical Engineering - From The
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4 Fig. 2. Process for retrieval inf
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6 Biomedical search engine Scientif
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10 Biomedical Engineering - From Th
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12 Bireme http://regional.bv salud.
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14 Semantic Networks analysis Biome
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100 Biomedical Engineering - From T
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108 Method (Detection) CIEF-tITP-CZ
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110 Method (Detection) Analyte Matr
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120 6. Conclusion Biomedical Engine
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150 5. Conclusions Biomedical Engin
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162 1 st phase : half year 4 2 nd p
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166 7. Innovative active training B
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172 12. Maturing projects’ story
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180 16. Acknowledgments Biomedical
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190 R* M M M M MR*M O O O O M O R*
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196 Fig. 9. Chemical structure of 5
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198 Relative Intensity (AU) Biomedi
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204 2. Preparation of IO nanopartic
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256 3. Deposition techniques Biomed
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300 2. Nanoparticles in biomedical
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454 In this case, the eigenvalues a
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456 where Biomedical Engineering -
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472 Nb b b l l1 Biomedical Engineer
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478 Load F (μN) Parallel-oriented
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