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Alternative Tumor-Targeting Strategies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
As with δ-aminolevulinate, methyl aminolevulinate is a relatively small molecule (i.e., molecular weight = 145.16) compared to the porfyrin-based agents and is a prodrug that undergoes metabolic conversion to photoactive porphyrins (e.g., protoporphyrin IX) which accumulate in the skin lesions and produce cytotoxic superoxide and hydroxyl radicals after irradiation with light of an appropriate energy and wavelength (e.g., ~37 J/cm² of narrowband red light of 630 nm, typically from an Aktilite CL128 lamp).
Monographs of Topical Drugs that Have Caused Contact Allergy/Allergic Contact Dermatitis
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
A 53-year-old woman with keratosis–ichthyosis–deafness (KID) syndrome presented with a long history of extensive hypertrophic lesions on both legs, which were treated with 15 sessions of photodynamic therapy (PDT) with aminolevulinic acid (ALA) as a photosensitizer. Seven years later, biopsies revealed multiple in situ squamous cell carcinomas. PDT with methyl aminolevulinate (MAL) cream was initiated. The topical drug was applied exclusively on the legs. The first session was unremarkable. However, 2 hours after the second session, performed 1 week later on the same skin area, the patient developed a generalized symmetric eruption with multiple erythematous and edematous pruritic papules and plaques on the trunk, arms, and legs. No obvious eczematous lesions were noted on treated sites. A similar eruption accompanied by intense pruritus occurred after the three following sessions, despite premedication with oral steroids. Older lesions later became hyperkeratotic and pigmented. Patch and photopatch tests showed UVA- and UVB-aggravated contact allergy to the cream. Patch tests showed weakly positive reactions (+) reactions on D2 and D3 with MAL 21% pet. and a negative reaction to the cream base and all ingredients. A diagnosis of systemic allergic contact dermatitis caused by MAL was made (2).
Skin
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Zbigniew W. Wojcinski, Lydia Andrews-Jones, Daher Ibrahim Aibo, Rie Kikkawa, Robert Dunstan
Numerous topically and systemically administered drugs of many different pharmacologic classes, including NSAIDs, antimicrobials, anticonvulsants, antihypertensive agents, and diuretics, have been associated with photosensitization in humans and animals. Some examples of photosensitizing drugs are phenothiazine, tetracyclines, sulfonamides, chlorpromazine, nalidixic acid, and fluorocoumarins (psoralens). Certain compounds have been developed specifically for their photosensitizing properties for use in photodynamic therapy. For example, methyl aminolevulinate hydrochloride is cytotoxic to precancerous and cancer cells upon activation by appropriate wavelength light (Health Canada 2009).
Proposition of standardized protocol for photodynamic therapy for vulvar lichen sclerosus
Published in Journal of Dermatological Treatment, 2022
Alicia Declercq, Canan Güvenç, Petra De Haes
We investigated relevant data concerning procedural details of the application of PDT. Overall, most of the studies used the photosensitizer 5-ALA while a few studies applied methyl aminolevulinate (MAL). Data with regard to study type and patient characteristics are displayed in Table 1 in a concise and stately manner. Table 2 gives more insight into the procedural details on how PDT was performed in the included articles. Table 3 provides information about the side effects before and after treatment. In the Appendices, the protocol can be found in more detail. The treatment of VLS with PDT remains a clinical challenge, until now there is no standardized treatment protocol about parameters, such as concentration of ALA, incubation time, light source (power and wavelength), exposure time (energy density and power density), and number and frequency of treatment repetitions to treat VLS. This narrative review gives an overview of procedural details of the application of PDT in order to develop a standardized treatment protocol for PDT in VLS.
Heme metabolism as a therapeutic target against protozoan parasites
Published in Journal of Drug Targeting, 2019
Guilherme Curty Lechuga, Mirian C. S. Pereira, Saulo C. Bourguignon
ALA-based PDT has a remarkable antiprotozoal activity against cutaneous leishmaniasis (CL; Figure 2). This self-limiting skin disease is caused by Leishmania spp., which is transmitted by the bite of the female sandfly. Symptoms include painless ulcers with an erythematous, indurate border or a crust surface that spontaneously heal but often produce disfiguring scars and hypopigmentation or hyperpigmentation. Some clinical studies demonstrated the effectiveness of ALA-based PDT for CL treatment [63,64]. A placebo-controlled, randomised study showed that treatment with 10% ALA PDT followed by red light (630 nm, 100 J/cm2) exposure was more effective than the paromomycin standard topical treatment [65]. Cure of a patient treated with methyl-aminolevulinate (MAL)-PDT has also been reported after frustrating therapeutic regimens to eliminate a resistant L. tropica [66]. Good cosmetic results are also an advantage of PDT treatment, although adverse effects including mild burning sensations occurred during the illumination. The long-term treatment and the need for specific medical equipment are also disadvantages of this therapy [64]. These obstacles in the treatment of CL have been overcome by the effective activation of PpIX in the daylight spectrum (DA-PDT) that effectively cured patients with skin lesions caused by L. major and L. tropica [67]. Among the advantages of DA-PDT is the elimination of the need for a specialised light source, a reduction of the absorption time with the photosensitizer, as well as easy and painless application.
Current developments in pharmacotherapy for actinic keratosis
Published in Expert Opinion on Pharmacotherapy, 2018
Elena Campione, Alessandra Ventura, Laura Diluvio, Mauro Mazzeo, Sara Mazzilli, Virginia Garofalo, Monia Di Prete, Luca Bianchi
A study compared the efficacy of both PDT and cryotherapy on AK lesions and demonstrated 91% complete response in the methyl aminolevulinate PDT group, 68% in the cryotherapy group and 30% in the placebo PDT group [72]. Methyl aminolevulinate PDT group was related to a higher occurrence of local reactions, such as erythema and burning sensation compared to the cryotherapy group. Complete response rates vary from 55.4% to 96.2% [64]. Pain during illumination and local skin reactions are the most common sites effect, however of short duration [73]. Using MAL PDT, more than 90% of patients showed a good or excellent cosmetic outcome. The treatment is easy to manage and it does not require local anesthesia. In conclusion, multicenter study showed PDT therapy to be superior to cryotherapy in terms of lesion response and cosmetic outcome [71,74].