Novel patch-based systems for the localised delivery of ALA-esters

Area of Science:

• Dermatology
• Photochemistry
• Materials Science

Background:

• Photodynamic therapy (PDT) utilizes light and photosensitizers to destroy targeted cells.
• Aminolaevulinic acid (ALA) is a common topical photosensitizer, but its skin penetration is limited, affecting treatment efficacy for lesions like nodular basal cell carcinomas.
• Improved drug delivery systems are needed to enhance ALA's therapeutic potential in PDT.

Purpose of the Study:

• To evaluate and compare the efficacy of ALA, methyl-ALA (m-ALA), and hexyl-ALA (h-ALA) when formulated in novel bioadhesive and pressure-sensitive adhesive (PSA) patch systems for PDT.
• To investigate the in vitro skin penetration and in vivo protoporphyrin IX (PpIX) induction capabilities of these ALA derivatives and delivery systems.

Main Methods:

• Equimolar concentrations of ALA, m-ALA, and h-ALA were incorporated into bioadhesive patch systems.
• In vitro penetration studies were conducted using excised porcine skin.
• In vivo studies in mice assessed PpIX fluorescence induction following topical application of the different patch formulations.

Main Results:

• In vitro studies showed ALA patches achieved higher tissue concentrations compared to m-ALA and h-ALA patches.
• In vivo, ALA was the most potent inducer of PpIX fluorescence, but h-ALA formulated in PSA patches yielded significantly higher PpIX levels than all bioadhesive systems.
• PSA patches with low h-ALA loadings effectively induced localized high PpIX levels, outperforming other formulations.

Conclusions:

• The choice of both the photosensitizer (ALA derivative) and the delivery system is crucial for optimizing PDT efficacy.
• Bioadhesive patches are suitable for moist skin environments, while h-ALA-loaded PSA patches enhance delivery to dry skin areas.
• The use of h-ALA in PSA patches may reduce the cost of clinical PDT due to lower required loadings.