Safety of Novel Amino-5-laevulinate Photosensitizer Precursors in Photodynamic Therapy for Healthy Human Skin

Neittaanmäki-Perttu, Noora; Neittaanmäki, Eerika; Pölönen, Ilkka; Snellman, Erna; Grönroos, Mari

doi:10.2340/00015555-2131

Cited by 5 publications

(8 citation statements)

References 10 publications

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“…Fluorescence images were taken at the beginning and end of illumination using a digital camera (Canon Ixus 130, 14.1 megapixel with the set-up ISO800, FW 2.8, no zoom), a Wood's light (Philips Burton â , Somerset, USA, kept handheld at a distance of about 8 cm) and a yellow filter lens (Hoya HMC, yellow-green xo, attached to the top of the Wood's light), as used by Neit-taanm€ aki-Perttu et al 21 The photosensitizer was removed with saline solution before imaging.…”

Section: Fluorescence Measurementmentioning

confidence: 99%

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Hexyl aminolevulinate, 5‐aminolevulinic acid nanoemulsion and methyl aminolevulinate in photodynamic therapy of non‐aggressive basal cell carcinomas: A non‐sponsored, randomized, prospective and double‐blinded trial

Salmivuori

Grönroos

Tani

et al. 2020

Acad Dermatol Venereol

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Background In the photodynamic therapy (PDT) of non-aggressive basal cell carcinomas (BCCs), 5-aminolevulinic acid nanoemulsion (BF-200ALA) has shown non-inferior efficacy when compared with methyl aminolevulinate (MAL), a widely used photosensitizer. Hexyl aminolevulinate (HAL) is an interesting alternative photosensitizer. To our knowledge, this is the first study using HAL-PDT in the treatment of BCCs. Objectives To compare the histological clearance, tolerability (pain and post-treatment reaction) and cosmetic outcome of MAL, BF-200 ALA and low-concentration HAL in the PDT of non-aggressive BCCs. Methods Ninety-eight histologically verified non-aggressive BCCs met the inclusion criteria, and 54 patients with 95 lesions completed the study. The lesions were randomized to receive LED-PDT in two repeated treatments with MAL, BF-200 ALA or HAL. Efficacy was assessed both clinically and confirmed histologically at three months by blinded observers. Furthermore, cosmetic outcome, pain, post-treatment reactions fluorescence and photobleaching were evaluated. Results According to intention-to-treat analyses, the histologically confirmed lesion clearance was 93.8% (95% confidence interval [CI] = 79.9-98.3) for MAL, 90.9% (95% CI = 76.4-96.9) for BF-200 ALA and 87.9% (95% CI = 72.7-95.2) for HAL, with no differences between the arms (P = 0.84). There were no differences between the arms as regards pain, post-treatment reactions or cosmetic outcome. Conclusions Photodynamic therapy with low-concentration HAL and BF-200 ALA has a similar efficacy, tolerability and cosmetic outcome compared to MAL. HAL is an interesting new option in dermatological PDT, since good efficacy is achieved with a low concentration.

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Section: Fluorescence Measurementmentioning

confidence: 99%

“…20 HAL, BF-200 ALA and MAL seem to be equally tolerated when applied on normal human skin. 21 This prospective trial aims to compare the efficacy and tolerability (i.e. pain and post-treatment-reaction) of MAL, BF-200 ALA and low-concentration HAL in the PDT of non-aggressive BCCs.…”

Section: Introductionmentioning

confidence: 99%

Hexyl aminolevulinate, 5‐aminolevulinic acid nanoemulsion and methyl aminolevulinate in photodynamic therapy of non‐aggressive basal cell carcinomas: A non‐sponsored, randomized, prospective and double‐blinded trial

Salmivuori

Grönroos

Tani

et al. 2020

Acad Dermatol Venereol

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“…Reduction of drug concentration and/or incubation time may also be considered for effective, less painful PDT, as may be employed for AK or acne . With the development of newer formulations of topical prodrugs and lower drug dose regimens, vigilance is required to ascertain whether any change in depth of effect and efficacy may also be associated with changes in pain experienced and tolerance of treatment …”

Section: Painmentioning

confidence: 99%

Adverse effects of topical photodynamic therapy: a consensus review and approach to management

et al. 2018

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“…Compared to ALA, HAL has an additional hexyl group that confers extra membrane permeability and higher bioavailability (Togsverd-Bo et al, 2012). HAL offers the advantages of low therapeutic concentrations, few side effects, and better economic value (Neittaanmäki-Perttu et al, 2016). Besides, HAL-mediated PDT has contributed to the diagnosis and treatment of tumors and skin diseases, such as bladder cancer (Helander et al, 2016) and solar keratosis (Neittaanmäki-Perttu et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Antifungal Photodynamic Activity of Hexyl-Aminolevulinate Ethosomes Against Candida albicans Biofilm

et al. 2020

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Biofilm formation is responsible for the development of chronic and recurrent Candida albicans infections. The generation of biofilms is commonly accompanied by high resistance to conventional antifungal drugs, which can increase up to 1,000-fold. Fortunately, antimicrobial photodynamic therapy (aPDT) has shown excellent potential to treat biofilm infections. However, the current most commonly used photosensitizer (PS), aminolevulinic acid (ALA), is hydrophilic, unstable, and has low permeability, leading to unsatisfactory effects on biofilm eradication. To solve these problems, more stable lipophilic PSs and more effective permeability carriers could be considered as two effective solutions. Hexylaminolevulinate (HAL) has good bioavailability as a PS, and we proved in a previous study that ethosomes (ES), lipid-based nanocarriers, promote percutaneous drug penetration. In our previous study, a HAL-ES system presented superior photodynamic effects compared to those of ALA or HAL alone. Therefore, here, we aim to evaluate the biological effects of HAL-ES-mediated aPDT on C. albicans biofilm. An XTT sodium salt assay showed that aPDT using 0.5% HAL decreased C. albicans biofilm activity by 69.71 ± 0.43%. Moreover, aPDT with 0.5% HAL-ES further decreased biofilm activity by 92.95 ± 0.16% and inhibited growth of 25.71 ± 1.61% within 48 h, mostly via its effect on the hyphae growth, which correlated with a threefold increase in C. albicans plasma membrane permeabilization. Notably, HAL-ES-mediated aPDT significantly reduced the sessile minimum inhibitory concentration 50 (SMIC50) of fluconazole to <2.0 μg/ml, and the 21-day survival rate of C. albicans biofilm-infected mice increased from 6.7 to 73.3%. It also significantly reduced the drug resistance and in vivo pathogenicity of C. albicans biofilm. These results demonstrate that HAL-ES-mediated aPDT could be an effective therapy for C. albicans biofilm infections; while also serving as a particularly promising effective treatment for cutaneous or mucocutaneous candidiasis and the prevention of progression to systemic candidiasis.

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Safety of Novel Amino-5-laevulinate Photosensitizer Precursors in Photodynamic Therapy for Healthy Human Skin

Cited by 5 publications

References 10 publications

Hexyl aminolevulinate, 5‐aminolevulinic acid nanoemulsion and methyl aminolevulinate in photodynamic therapy of non‐aggressive basal cell carcinomas: A non‐sponsored, randomized, prospective and double‐blinded trial

Hexyl aminolevulinate, 5‐aminolevulinic acid nanoemulsion and methyl aminolevulinate in photodynamic therapy of non‐aggressive basal cell carcinomas: A non‐sponsored, randomized, prospective and double‐blinded trial

Adverse effects of topical photodynamic therapy: a consensus review and approach to management

Antifungal Photodynamic Activity of Hexyl-Aminolevulinate Ethosomes Against Candida albicans Biofilm

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