Nanoscopic micelle delivery improves the photophysical properties and efficacy of photodynamic therapy of protoporphyrin IX.

Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Journal of Controlled Release (Impact Factor: 7.71). 05/2011; 151(3):271-7. DOI: 10.1016/j.jconrel.2011.01.004
Source: PubMed


Nanodelivery systems have shown considerable promise in increasing the solubility and delivery efficiency of hydrophobic photosensitizers for photodynamic therapy (PDT) applications. In this study, we report the preparation and characterization of polymeric micelles that incorporate protoporphyrin IX (PpIX), a potent photosensitizer, using non-covalent encapsulation and covalent conjugation methods. Depending on the incorporation method and PpIX loading percentage, PpIX existed as a monomer, dimer or aggregate in the micelle core. The PpIX state directly affected the fluorescence intensity and (1)O(2) generation efficiency of the resulting micelles in aqueous solution. Micelles with lower PpIX loading density (e.g. 0.2%) showed brighter fluorescence and higher (1)O(2) yield than those with higher PpIX loading density (e.g. 4%) in solution. However, PDT efficacy in H2009 lung cancer cells showed an opposite trend. In particular, 4% PpIX-conjugated micelles demonstrated the largest PDT therapeutic window, as indicated by the highest phototoxicity and relatively low dark toxicity. Results from this study contribute to the fundamental understanding of nanoscopic structure-property relationships of micelle-delivered PpIX and establish a viable micelle formulation (i.e. 4% PpIX-conjugated micelles) for in vivo evaluation of antitumor efficacy.

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    • "Protoporphyrin IX has an absorption maximum at 352 nm (e.g. Ding et al., 2011). Subsequent Raman spectroscopy measurements of the brown eggshells performed with 351 nm excitation produced useful resonance Raman spectra (Fig. 1). "
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    ABSTRACT: Avian eggshells are variable in appearance, including colouration. Here we demonstrate that Raman spectroscopy can provide accurate diagnostic information about major eggshell constituents, including the pigments biliverdin and protoprophyrin IX. Eggshells pigmented with biliverdin showed a series of pigment-diagnostic Raman peaks under 785 nm excitation. Eggshells pigmented with protoporphyrin IX showed strong emission under 1064 nm and 785 nm excitation, whereas resonance Raman spectra (351 nm excitation) showed a set of protoporphyrin IX informative peaks characterisitic of protoporphyrin IX. As representative examples, we identified biliverdin in the olive green eggshells of elegant crested tinamous (Eudromia elegans) and in the blue eggshells of extinct upland moa (Megalapteryx didinus). This study encourages the wider use of Raman spectroscopy in pigment and colouration research and highlights the value of this technique for non-destructive analyses of museum eggshell specimens. © 2015. Published by The Company of Biologists Ltd.
    Journal of Experimental Biology 06/2015; 218(Pt 17). DOI:10.1242/jeb.124917 · 2.90 Impact Factor
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    • "Hydrophobic PS should be formulated in a convenient aqueous drug delivery system to avoid its self-aggregation. Aqueous micelles constitute efficient drug delivery systems [11] [12] [13] [14]. Among surfactants applied in drug formulation, we highlight the amphiphilic polymeric molecules based on alkylene oxide monomers due to their biocompatibility, low toxicity, large binding sites and protection of the incorporated drugs against the immunologic biological system [15] [16]. "
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    ABSTRACT: In this paper, the physicochemical and photophysical properties of xanthene dyes interacting with micelles were evaluated. Xanthenes are potential photosensitizers for photodynamic therapy. The dyes were eosin Y and its ester derivatives with methyl, butyl and decyl alkyl groups. In aqueous media at physiological pH eosin is present as dianionic protolytic form while its esters are monoanionic. Analysis of the water/octanol partition coefficient showed that the eosin is the most hydrophilic compound and the hydrophobicity increases as the alkyl chain of the ester increases: eosin < methyl ester < butyl ester < decyl ester. Computational calculations of the dipole moments, molecular volume, charge distribution, solvation energy and molecular orbital performed by the B3LYP/DGDZVP method and IEFPCM solvent model, allowed to justify the electronic absorption properties and its dependence with the dye environment. In order to mimic the interaction of these compounds with membranes, it was used micelles of sodium dodecyl sulfate (SOS), cetyl trimethylammonium bromide (CTAB) and polymeric micelles (Pluronics((R))) of P-123 and F-127. The binding constant between the xanthenes and micelles increased with the hydrophobicity of the dye in all evaluated systems. Furthermore, we observed the formation of pre-micellar aggregates when using cationic CTAB micelles due to electrostatic attraction. The iodide fluorescence quenching showed that the more hydrophobic photosensitizer were located deeply within the micelles. The fluorescence quantum yield values increased in the presence of surfactants, indicating protection against non-radiative deactivation. The dyes singlet oxygen quantum yield values suffered a small decrease when formulated in micelles, however they are still suitable for photodynamic applications. The results show that eosin and its ester derivatives have favorable characteristics for use in photodynamic therapy, particularly formulated in biocompatible polymeric surfactants such as Pluronics((R)).
    Journal of Photochemistry and Photobiology A Chemistry 08/2014; 287. DOI:10.1016/j.jphotochem.2014.04.015 · 2.50 Impact Factor
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    • "Several methods have been suggested for improving ALA transdermal delivery, which include microneedles, patch-based systems, microemulsions, iontophoresis, and laser.7,20–22 Extensive research has also been carried out to develop NP drug delivery systems for ALA,8–11 but PLGA NPs have not been tested for ALA delivery before. "
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    ABSTRACT: 5-Aminolevulinic acid (ALA) is a prodrug for topical photodynamic therapy. The effectiveness of topical ALA can be limited by its bioavailability. The aim of this study was to develop a novel ALA delivery approach using poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). A modified double emulsion solvent evaporation method was used to prepare ALA loaded PLGA NPs (ALA PLGA NPs). The characteristics, uptake, protoporphyrin IX fluorescence kinetics, and cytotoxicity of ALA PLGA NPs toward a human skin squamous cell carcinoma cell line were examined. The mean particle size of spherical ALA PLGA NPs was 65.6 nm ± 26 nm with a polydispersity index of 0.62. The encapsulation efficiency was 65.8% ± 7.2% and ALA loading capacity was 0.62% ± 0.27%. When ALA was dispersed in PLGA NPs, it turned into an amorphous phase. ALA PLGA NPs could be taken up by squamous cell carcinoma cells and localized in the cytoplasm. The protoporphyrin IX fluorescence kinetics and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay showed that ALA PLGA NPs were more effective than free ALA of the same concentration. PLGA NPs provide a promising ALA delivery strategy for topical ALA-photodynamic therapy of skin squamous cell carcinoma.
    International Journal of Nanomedicine 07/2013; 8:2669-76. DOI:10.2147/IJN.S45821 · 4.38 Impact Factor
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