Pretreatment to Enhance Protoporphyrin IX Accumulation in Photodynamic Therapy

Abstract

The response rates of photodynamic therapy (PDT) vary widely. Limited uptake of topically applied 5-aminolaevulinic acid (ALA), or its methyl ester (MAL), and suboptimal production of protoporphyrin IX (PpIX) may account for these differences. Recently, we demonstrated that hyperkeratosis is an important negative factor in ALA uptake. This review has its focus on pretreatment of the skin in order to improve the clinical outcome of ALA/MAL PDT. Pretreatment of hyperkeratosis can be achieved with keratolytics, curettage/debulking, tape stripping, microdermabrasion or laser ablation. Penetration enhancers may alter the composition or organization of the intercellular lipids of the stratum corneum. Several studies have been performed on the use of dimethyl sulfoxide, azone, glycolic acid, oleic acid and iontophoresis to increase the penetration of ALA. As PpIX production is also dominated by temperature-dependent processes, elevating skin temperature during ALA application may also improve treatment results. Another approach is the use of additives that interact with the heme biosynthetic pathway, e.g. by removing ferrous iron with iron-chelating substances such as: ethylenediaminetetraacetic acid; 3-hydroxypyridin-4-ones; 1,2-diethyl-3-hydroxypyridin-4-one-hydrochloride; and desferrioxamine. In conclusion, simple pretreatments or additions to the regular practice of PDT, aimed to optimize intralesional PpIX content, improve the clinical outcome.

Oil components modulate the skin delivery of 5-aminolevulinic acid and its ester prodrug from oil-in-water and water-in-oil nanoemulsions

“…Another drawback for topical ALA delivery is the marked inter-and intra-subject variations that occur in human skin. 25 A similar result was observed in the present work for the ALA-loaded aqueous control. With no reproducible control over ALA permeation to neoplastic lesions, it is inevitable that potential variations in therapeutic outcomes after PDT may become difficult to reconcile.…”

Fractional CO2 laser‐assisted drug delivery

“…So far, several attempts have been taken to improve ALA/MAL bioavailability at deeper skin layers. Among others, these include iontophoresis, ultrasound, microneedle puncture, temperature elevation as well as removal of hyperkeratosis and stratum corneum with curettage, tape stripping, microdermabrasion and laser ablation [17,23]. Conventional Er:YAG laser ablation of stratum corneum and superficial epidermis enhanced PpIX accumulation in murine superficial skin layers and subcutaneous tumors as well as ALA penetration of in vivo porcine skin [19,20].…”

“…(e.g., drug-vehicle optimization, prodrugs, liposomes, hydration, and chemical enhancers) as well as physical modulation techniques such as iontophoresis, electroporation, ultrasound, photomechanical waves, microneedles, and superficial laser ablation [15][16][17]. Erbium lasers in particular have been used for laser-assisted cutaneous drug delivery [18][19][20][21], but the potential for deep AFR-assisted drug delivery has not been studied.…”

Radiant near infrared light emitting Diode exposure as skin preparation to enhance photodynamic therapy inflammatory type acne treatment outcome

“…IR pre-treatment with ALA-PDT was shown to produce notable results with limited side effects after only one treatment, thereby limiting concerns over patient compliance. Moreover, it is very easy to perform in a clinical setting, and less invasive than other pre-treatment modalities (e.g., microdermabrasion) [34]. The use of IR-PDT in acne might prove to reduce the need for long-term conventional treatments, such as antibiotic use associated with the growing potential of inducing antibiotic-resistant bacteria and retinoid systemic side effects.…”