Epidermal penetration and protoporphyrin IX formation of two different 5-aminolevulinic acid formulations in ex vivo human skin

Schmitz, Lutz; Novak, Ben; Hoeh, A K; Luebbert, H; Dirschka, Thomas

doi:10.1016/j.pdpdt.2015.11.004

Cited by 25 publications

(20 citation statements)

References 22 publications

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“…In human skin explants, BF-200 ALA was compared with a standard 20% ALA cream formulation. The amount of ALA-induced PpIX was at least threefold higher at any measured time point [53]. Two additional studies could reproduce the increased PpIX formation attributed to BF-200 ALA compared with MAL in healthy volunteers' skin, focusing on either different age groups or pretreatments [66,67].…”

Section: Enhancing Pdt With Nanoemulsion Technologymentioning

confidence: 95%

“…Interestingly, the nanoemulsion BF-200 seems to enhance penetration as well as epidermal PpIX formation [53,64,66,67]. In a porcine skin model in vitro, BF-200 ALA containing 7.8% ALA was shown to be superior compared with a 20% MAL formulation, containing 16% free MAL, in terms of penetration depth and PpIX formation in the deeper epidermal layers [64].…”

Section: Enhancing Pdt With Nanoemulsion Technologymentioning

confidence: 97%

“…Two factors that are essential for ALA-based PDT are stability and epidermal penetration of the prodrug [53]. Stability of topical ALA preparations is critical, as ALA has been shown to be prone to degradation to 2.5-(betacarboxyethyl)-dihydropyrazine and 2.5-(beta-carboxyethyl)-pyrazine in aqueous solutions [54].…”

Section: Enhancing Pdt With Nanoemulsion Technologymentioning

confidence: 99%

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A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

Reinhold¹

2017

Future Oncol.

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BF-200 ALA is a combination of a nanoscale-lipid vesicle formulation and the prodrug 5-aminolevulinic acid (5-ALA). The nanoemulsion stabilizes the prodrug and enhances its penetration through the stratum corneum. It has shown excellent therapeutic results in both lesion and field-directed photodynamic therapy of actinic keratosis (AK). AK is an early form of epidermal neoplasia and a precursor of invasive cutaneous squamous cell carcinoma. It is characterized by the combination of visible neoplastic lesions and surrounding tissue also harboring tumorigenic UV-induced mutations: a concept called field cancerization. A selective, field-directed treatment is ideal to meet the requirements of field change. Here, we review the clinical data on BF-200 ALA for AK along with a summary of molecular mechanisms and future perspectives. Actinic keratosis (AK), also known as solar keratosis, is caused by chronic exposure to sunlight or other ultraviolet light sources [1,2] and may progress to invasive squamous cell carcinoma (SCC) [3]. It is the most common lesion with malignant potential to arise on the skin. AK is mostly seen in Caucasians in skin areas that have extensive sun exposure throughout their lives [4]. Epidemiological data show a high occurrence rate of AK. Regions with higher ultraviolet exposure have a higher prevalence of AK. For the USA, the prevalence was estimated to range from 11 to 26%, while in Australia it ranged from 40 to 60%. In Europe, a prevalence of 15% in men and 6% in women has been documented [5]. Over the age of 70 years, 34% of men and 18% of women were found to have actinic keratotic lesions [6]. Next to fair skin type, an advanced age and lifelong sun exposure immunosuppression/-deficiency plays another important risk factor [5].Mostly, AK develops slowly and early in the disease process, they may disappear only to reappear later. Recurrence of the disease may include partial elimination of the initial lesion, subclinical lesion progression to visible status, or development of new lesions [7]. On top of this, an AK may progress to invasive SCC, the second-most common form of skin cancer [8,9]. The actual percentage of progress to invasive SCC remains unknown, and estimates vary from 5 to 20% within 10 to 25 years with reported annual transformation rates varying greatly from as low as 0.25% to as high as 16% [10]. The regression rate for a single untreated lesion is 15 to 63% after a year; recurrence rates range from 15 to 53% [11]. In general patients develop multiple AKs in one area and predicting which course each individual lesion will follow is impossible. Nonetheless, AK lesions are reliable markers for patients who are most predisposed to developing invasive SCC [4,[12][13].AK lesions typically appear in areas most frequently exposed to the sun such as the face, back of the hands, or bald scalp; 75% of lesions are found on the head, neck and forearms [14]. The lesions vary in appearance as well as size and can include erythematous scaly macules, rough pigmented patches and hyperker...

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Section: Enhancing Pdt With Nanoemulsion Technologymentioning

confidence: 95%

Section: Enhancing Pdt With Nanoemulsion Technologymentioning

confidence: 97%

Section: Enhancing Pdt With Nanoemulsion Technologymentioning

confidence: 99%

See 1 more Smart Citation

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

Reinhold¹

2017

Future Oncol.

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“…BF‐200 ALA is a topically applied nanoemulsion‐based gel that contains 7·8% 5‐aminolaevulinic acid (ALA). The formulation improves the stability of ALA and enhances epidermal penetration compared with other formulations . Thus, the concentration of the active substance could be significantly reduced.…”

mentioning

confidence: 99%

“…The formulation improves the stability of ALA and enhances epidermal penetration compared with other formulations. 21,22 Thus, the concentration of the active substance could be significantly reduced. In the reported clinical study, BF-200 ALA was compared with a cream containing 16% methyl aminolaevulinic acid (MAL) using a noninferiority trial design.…”

mentioning

confidence: 99%

A randomized, multinational, noninferiority, phase III trial to evaluate the safety and efficacy of BF-200 aminolaevulinic acid gel vs. methyl aminolaevulinate cream in the treatment of nonaggressive basal cell carcinoma with photodynamic therapy

Morton

Dominicus²,

Radny

et al. 2018

Br J Dermatol

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Clinical Pharmacokinetics and Safety of a 10% Aminolevulinic Acid Hydrochloride Nanoemulsion Gel (BF‐200 ALA) in Photodynamic Therapy of Patients Extensively Affected With Actinic Keratosis: Results of 2 Maximal Usage Pharmacokinetic Trials

Novak

DuBois

Chahrour³

et al. 2021

Clinical Pharm in Drug Dev

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The nanoemulsion-based 10% aminolevulinic acid (ALA) hydrochloride gel BF-200 ALA optimizes epidermal penetration of its active ingredient and is approved for topical photodynamic therapy (PDT) for the treatment of actinic keratosis in the United States and Europe. To characterize systemic absorption from dermal application during PDT, ALA and its key active metabolite protoporphyrin IX (PpIX) were analyzed in 2 maximal usage pharmacokinetic trials (MUsT) in patients severely affected with actinic keratosis. The primary objective of both MUsTs was to assess baseline-adjusted plasma concentration-time curves for ALA and PpIX after a single PDT treatment applying either 2 g (1 tube) of BF-200 ALA on the face (MUsT-1) or applying 6 g (3 tubes) of BF-200 ALA on the face/scalp or body periphery (MUsT-2), to 20 or 60 cm 2 , respectively. All PDTs were performed using red light at around 635 nm wavelength. Safety and tolerability were documented along with pharmacokinetics. In both MUsTs, ALA plasma concentrations were transiently increased to a maximum concentration at about 2.5 to 3.3 times above endogenous baseline with time to maximum concentration at ≈3 hours after dosing. Plasma levels subsequently returned to baseline within 10 hours after dosing. Overall baselineadjusted mean area under the baseline-adjusted plasma concentration-time curve from time zero to the last sampling time point at which the concentration was at or above the lower limit of quantification ranged from 142.8 to 146.2, indicating that a similar, minor fraction of topical ALA is systemically absorbed under both dosing regimens. Systemic PpIX exposure after administration of either dose of BF-200 ALA was equally minimal. Application site skin reactions were treatment area size-related, albeit transient and consistent with the known safety profile of BF-200 ALA.

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Epidermal penetration and protoporphyrin IX formation of two different 5-aminolevulinic acid formulations in ex vivo human skin

Cited by 25 publications

References 22 publications

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

A randomized, multinational, noninferiority, phase III trial to evaluate the safety and efficacy of BF-200 aminolaevulinic acid gel vs. methyl aminolaevulinate cream in the treatment of nonaggressive basal cell carcinoma with photodynamic therapy

Clinical Pharmacokinetics and Safety of a 10% Aminolevulinic Acid Hydrochloride Nanoemulsion Gel (BF‐200 ALA) in Photodynamic Therapy of Patients Extensively Affected With Actinic Keratosis: Results of 2 Maximal Usage Pharmacokinetic Trials

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