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  1. Greco G, Di Piazza S, Chan J, Zotti M, Hanna R, Gheno E, et al.
    Photodiagnosis Photodyn Ther, 2020 Mar;29:101575.
    PMID: 31614222 DOI: 10.1016/j.pdpdt.2019.10.010
    BACKGROUND: A large number of systemic diseases can be linked to oral candida pathogenicity. The global trend of invasive candidiasis has increased progressively and is often accentuated by increasing Candida albicans resistance to the most common antifungal medications. Photodynamic therapy (PDT) is a promising therapeutic approach for oral microbial infections. A new formulation of 5-aminolevulinic acid (5%ALA) in a thermosetting gel (t) (5%ALA-PTt) was patented and recently has become available on the market. However, its antimicrobial properties, whether mediated or not by PDT, are not yet known. In this work we characterised them.

    METHODS: We isolated a strain of C. albicans from plaques on the oral mucus membrane of an infected patient. Colonies of this strain were exposed for 1 24 h, to 5%ALA-PTt, 5%ALA-PTt buffered to pH 6.5 (the pH of the oral mucosa) (5%ALA-PTtb) or not exposed (control). The 1 h-exposed samples were also irradiated at a wavelength of 630 nm with 0.14 watts (W) and 0.37 W/cm2 for 7 min at a distance of <1 mm.

    RESULTS AND CONCLUSION: The 5% ALA-PTt preparation was shown to be effective in reducing the growth of biofilm and inoculum of C. albicans. This effect seems to be linked to the intrinsic characteristics of 5%ALA-TPt, such acidic pH and the induction of free radical production. This outcome was significantly enhanced by the effect of PDT at relatively short incubation and irradiation times, which resulted in growth inhibition of both treated biofilm and inoculum by ∼80% and ∼95%, respectively.

    Matched MeSH terms: Photosensitizing Agents/administration & dosage
  2. Akram Z, Al-Shareef SA, Daood U, Asiri FY, Shah AH, AlQahtani MA, et al.
    Photomed Laser Surg, 2016 Apr;34(4):137-49.
    PMID: 26982216 DOI: 10.1089/pho.2015.4076
    The aim of this study was to assess the bactericidal efficacy of antimicrobial photodynamic dynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) against periodontal pathogens.
    Matched MeSH terms: Photosensitizing Agents/administration & dosage*
  3. Md S, Haque S, Madheswaran T, Zeeshan F, Meka VS, Radhakrishnan AK, et al.
    Drug Discov Today, 2017 Aug;22(8):1274-1283.
    PMID: 28456749 DOI: 10.1016/j.drudis.2017.04.010
    Topical photodynamic therapy (PDT) is a non-invasive technique used in the treatment of malignant and non-malignant skin diseases. It offers great promise because of its simplicity, enhanced patient compliance, localisation of the photosensitizer, as well as the use of light and oxygen to achieve photocytotoxicity. Despite progress in photosensitizer-mediated topical PDT, its clinical application is limited by poor penetration of photosensitizers through the skin. Therefore, much effort has been made to develop nanocarriers that can tackle the challenges of conventional photosensitizer-mediated PDT for topical delivery. This review discusses recent data on the use of different types of lipid-based nanocarriers in delivering photosensitizer for topical PDT.
    Matched MeSH terms: Photosensitizing Agents/administration & dosage*
  4. Qidwai A, Khan S, Md S, Fazil M, Baboota S, Narang JK, et al.
    Drug Deliv, 2016 May;23(4):1476-85.
    PMID: 26978275 DOI: 10.3109/10717544.2016.1165310
    Topical photodynamic therapy (PDT) is a promising alternative for malignant skin diseases such as basal-cell carcinoma (BCC), due to its simplicity, enhanced patient compliance, and localization of the residual photosensitivity to the site of application. However, insufficient photosensitizer penetration into the skin is the major issue of concern with topical PDT. Therefore, the aim of the present study was to enable penetration of photosensitizer to the different strata of the skin using a lipid nanocarrier system. We have attempted to develop a nanostructured lipid carrier (NLC) for the topical delivery of second-generation photosensitizer, 5-amino levulinic acid (5-ALA), whose hydrophilicity and charge characteristic limit its percutaneous absorption. The microemulsion technique was used for preparing 5-ALA-loaded NLC. The mean particle size, polydispersity index, and entrapment efficiency of the optimized NLC of 5-ALA were found to be 185.2 ± 1.20, 0.156 ± 0.02, and 76.8 ± 2.58%, respectively. The results of in vitro release and in vitro skin permeation studies showed controlled drug release and enhanced penetration into the skin, respectively. Confocal laser scanning microscopy and cell line studies respectively demonstrated that encapsulation of 5-ALA in NLC enhanced its ability to reach deeper skin layers and consequently, increased cytotoxicity.
    Matched MeSH terms: Photosensitizing Agents/administration & dosage*
  5. Renninger M, Fahmy O, Schubert T, Schmid MA, Hassan F, Stenzl A, et al.
    World J Urol, 2020 Feb;38(2):397-406.
    PMID: 31030231 DOI: 10.1007/s00345-019-02780-0
    PURPOSE: To investigate whether hexaminolevulinate-based (HAL) bladder tumor resection (TURBT) impacts on outcomes of patients with primary non-muscle-invasive bladder cancer (NMIBC) who were eventually treated with radical cystectomy (RC).

    METHODS: A total of 131 consecutive patients exhibiting NMIBC at primary diagnosis were retrospectively investigated whether they had undergone any HAL-guided TURBT prior to RC. Uni- and multivariable analyses were used to evaluate the impact of HAL-TURBT on cancer-specific (CSS) and overall survival (OS). The median follow-up was 38 months (IQR 13-56).

    RESULTS: Of the 131 patients, 69 (52.7%) were managed with HAL- and 62 (47.3%) with white light (WL)-TURBT only prior to RC. HAL-TURBT was associated with a higher number of TURBTs prior to RC (p = 0.002) and administration of intravesical chemotherapy (p = 0.043). A trend towards a higher rate of tumor-associated immune cell infiltrates in RC specimens (p = 0.07) and a lower utilization rate of post-operative systemic chemotherapy (p = 0.10) was noted for patients who were treated with HAL-TURBT. The 5-year CSS/OS was 90.9%/74.5% for the HAL-group and 73.8%/55.8% for the WL-group (p = 0.042/0.038). In multivariable analysis, lymph node tumor involvement (p = 0.007), positive surgical margins (p = 0.001) and performance of WL-TURBT only (p = 0.040) were independent predictors for cancer-specific death.

    CONCLUSIONS: The present data suggest that the resection of NMIBC under HAL exerts a beneficial impact on outcomes of patients who will need to undergo RC during their course of disease. This finding may be due to improved risk stratification as the resection under HAL may allow more patients to be treated timely and adequately.

    Matched MeSH terms: Photosensitizing Agents/administration & dosage*
  6. Topkaya D, Ng SY, Bretonnière Y, Lafont D, Chung LY, Lee HB, et al.
    Photodiagnosis Photodyn Ther, 2016 Dec;16:12-14.
    PMID: 27475243 DOI: 10.1016/j.pdpdt.2016.07.008
    Matched MeSH terms: Photosensitizing Agents/administration & dosage
  7. Akram Z, Abduljabbar T, Sauro S, Daood U
    Photodiagnosis Photodyn Ther, 2016 Dec;16:142-153.
    PMID: 27619532 DOI: 10.1016/j.pdpdt.2016.09.004
    BACKGROUND: To assess the efficacy of antimicrobial photodynamic therapy (aPDT) or laser therapy (LT) alone as an adjunct to scaling and root planing (SRP) on the gingival crevicular fluid (GCF) inflammatory proteins in periodontal disease.

    METHODS: Databases (MEDLINE via PubMed; EMBASE; Cochrane Central Register of Controlled Trials and Cochrane Oral Health Group Trials Register databases) were searched from 1980 up to and including July 2016. The addressed PICO question was: "What effect does aPDT and/or LT as an adjunct to SRP have on the GCF inflammatory proteins in periodontal disease patients?"

    RESULTS: Eight studies used aPDT while 10 studies used laser alone. Eight cytokines including tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10, interferon gamma (IFN-γ), matrix metalloproteinase (MMP)-8 and granulocyte colony-stimulating factor (GM-CSF) were eligible for qualitative analysis for aPDT and LT studies. Four aPDT studies showed significant reduction in IL-1β while one study showed significant reduction in TNF-α levels after aPDT application at follow-up. One study showed significant reduction of IFN-γ, IL-8 and GM-CSF levels after aPDT at follow-up. IL-1β significantly reduced in 4 LT studies, while one study showed significant decrease for IL-6 and TIMP-1 levels. MMP-8 and TNF-α showed significant reduction in three and one study respectively.

    CONCLUSION: It remains debatable whether adjunctive aPDT or LT is effective in the reduction of GCF inflammatory proteins in periodontal disease due to non-standard laser parameters and short follow up period. These findings should be considered preliminary and further studies with long-term follow up and standardized laser parameters are recommended.

    Matched MeSH terms: Photosensitizing Agents/administration & dosage
  8. Cheah HY, Gallon E, Dumoulin F, Hoe SZ, Japundžić-Žigon N, Glumac S, et al.
    Mol Pharm, 2018 07 02;15(7):2594-2605.
    PMID: 29763568 DOI: 10.1021/acs.molpharmaceut.8b00132
    We previously developed a new zinc(II) phthalocyanine (ZnPc) derivative (Pc 1) conjugated to poly-L-glutamic acid (PGA) (1-PG) to address the limitations of ZnPc as part of an antitumor photodynamic therapy approach, which include hydrophobicity, phototoxicity, and nonselectivity in biodistribution and tumor targeting. During this study, we discovered that 1-PG possessed high near-infrared (NIR) light absorptivity (λmax = 675 nm), good singlet oxygen generation efficiency in an aqueous environment, and enhanced photocytotoxic efficacy and cancer cell uptake in vitro. In the current study, we discovered that 1-PG accumulated in 4T1 mouse mammary tumors, with a retention time of up to 48 h. Furthermore, as part of an antitumor PDT, low dose 1-PG (2 mg of Pc 1 equivalent/kg) induced a greater tumor volume reduction (-74 ± 5%) when compared to high dose ZnPc (8 mg/kg, -50 ± 12%). At higher treatment doses (8 mg of Pc 1 equivalent/kg), 1-PG reduced tumor volume maximally (-91 ± 6%) and suppressed tumor size to a minimal level for up to 15 days. The kidney, liver, and lungs of the mice treated with 1-PG (both low and high doses) were free from 4T1 tumor metastasis at the end of the study. Telemetry-spectral-echocardiography studies also revealed that PGA (65 mg/kg) produced insignificant changes to the cardiovascular physiology of Wistar-Kyoto rats when administered in vivo. Results indicate that PGA displays an excellent cardiovascular safety profile, underlining its suitability for application as a nanodrug carrier in vivo. These current findings indicate the potential of 1-PG as a useful photosensitizer candidate for clinical PDT.
    Matched MeSH terms: Photosensitizing Agents/administration & dosage*
  9. Lim TH, Lai TYY, Takahashi K, Wong TY, Chen LJ, Ruamviboonsuk P, et al.
    JAMA Ophthalmol, 2020 09 01;138(9):935-942.
    PMID: 32672800 DOI: 10.1001/jamaophthalmol.2020.2443
    Importance: The 2-year efficacy and safety of combination therapy of ranibizumab administered together with verteporfin photodynamic therapy (vPDT) compared with ranibizumab monotherapy in participants with polypoidal choroidal vasculopathy (PCV) are unclear.

    Objective: To compare treatment outcomes of ranibizumab, 0.5 mg, plus prompt vPDT combination therapy with ranibizumab, 0.5 mg, monotherapy in participants with PCV for 24 months.

    Design, Setting, and Participants: This 24-month, phase IV, double-masked, multicenter, randomized clinical trial (EVEREST II) was conducted among Asian participants from August 7, 2013, to March 2, 2017, with symptomatic macular PCV confirmed using indocyanine green angiography.

    Interventions: Participants (N = 322) were randomized 1:1 to ranibizumab, 0.5 mg, plus vPDT (combination therapy group; n = 168) or ranibizumab, 0.5 mg, plus sham PDT (monotherapy group; n = 154). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT (combination group) or sham PDT (monotherapy group) on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions.

    Main Outcomes and Measures: Evaluation of combination therapy vs monotherapy at 24 months in key clinical outcomes, treatment exposure, and safety. Polypoidal lesion regression was defined as the absence of indocyanine green hyperfluorescence of polypoidal lesions.

    Results: Among 322 participants (mean [SD] age, 68.1 [8.8] years; 225 [69.9%] male), the adjusted mean best-corrected visual acuity (BCVA) gains at month 24 were 9.6 letters in the combination therapy group and 5.5 letters in the monotherapy group (mean difference, 4.1 letters; 95% CI, 1.0-7.2 letters; P = .005), demonstrating that combination therapy was superior to monotherapy by the BCVA change from baseline to month 24. Combination therapy was superior to monotherapy in terms of complete polypoidal lesion regression at month 24 (81 of 143 [56.6%] vs 23 of 86 [26.7%] participants; P 

    Matched MeSH terms: Photosensitizing Agents/administration & dosage
  10. Makhadmeh GN, Abdul Aziz A, Abdul Razak K, Abu Noqta O
    IET Nanobiotechnol, 2015 Dec;9(6):381-5.
    PMID: 26647815 DOI: 10.1049/iet-nbt.2015.0003
    This study analysed the physical effects of Cichorium Pumilum (CP), as a natural photosensitizer (PS), and Protoporphyrin IX (PpIX), as a synthetic PS, encapsulated with silica nanoparticles (SiNPs) in photodynamic therapy. The optimum concentrations of CP and PpIX, needed to destroy Red Blood Cells (RBC), were determined and the efficacy of encapsulated CP and PpIX were compared with naked CP and PpIX was verified. The results confirmed the applicability of CP and PpIX encapsulated in SiNPs on RBCs, and established a relationship between the encapsulated CP and PpIX concentration and the time required to rupture 50% of the RBCs (t50). The CP and PpIX encapsulated in SiNPs exhibited higher efficacy compared with that of naked CP and PpIX, respectively, and CP had less efficacy compared with PpIX.
    Matched MeSH terms: Photosensitizing Agents/administration & dosage
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