Drug Delivery of Aminolevulinic Acid from Topical Formulations Intended for Photodynamic Therapy¶

Abstract

Topical photodynamic therapy is used for a variety of malignant and pre-malignant skin disorders, including Bowen's Disease and Superficial Basal Cell Carcinoma. A haem precursor, typically 5-aminolevulinic acid (ALA), acting as a prodrug, is absorbed and converted by the haem biosynthetic pathway to photoactive protoprophyrin IX (PpIX), which accumulates preferentially in rapidly dividing cells. Cell destruction occurs when PpIX is activated by an intense light source of appropriate wavelength. Topical delivery of ALA avoids the prolonged photosensitivity reactions associated with systemic administration of photosensitisers but its clinical utility is influenced by the tissue penetration characteristics of the drug, its ease of application and the stability of the active agent in the applied dose. This review, therefore, focuses on drug delivery applications for topical, ALA-based PDT. Issues considered in detail include physical and chemical enhancement strategies for tissue penetration of ALA and subsequent intracellular accumulation of PpIX, together with formulation strategies and drug delivery design solutions appropriate to various clinical applications. The fundamental aspects of drug diffusion in relation to the physicochemical properties of ALA are reviewed and specific consideration is given to the degradation pathways of ALA in formulated systems that, in turn, influence the design of stable topical formulations.

Photodynamic therapy based on 5‐aminolevulinic acid and its use as an antimicrobial Agent

“…115 In addition, novel delivery systems, designed to improve the efficacy of topical ALA application have been developed, including: sprays, 116 microemulsions, 117,118 micro-needle arrays, 119,120 and purpose-designed dosage systems such as cream formulations containing penetration enhancers and/or iron chelators. 101,102,115 Creams based on ALA and several of its derivatives have gained marketing authorization in a number of countries around the world for the treatment of nonmelanoma skin cancers 121,122 but none, as yet, are licensed for use in an antimicrobial context. 55 For the treatment of bodily areas less amenable to topical application, systems based on pressure sensitive patches and bioadhesive patches, which adhere to the skin, have recently been developed.…”

“…55 For the treatment of bodily areas less amenable to topical application, systems based on pressure sensitive patches and bioadhesive patches, which adhere to the skin, have recently been developed. 101,102,115,123 Using these in vivo systems and various in vitro methodologies, ALA-based PDT has recently been investigated for the ability to inactivate a range of microbes and to remedy their infections (Tables I-III). 130,190…”

Quantification of 5‐aminolevulinic acid by CE using dynamic pH junction technique

“…Curve a (50 mM BGE) shows the unsatisfactory focusing effect due to its higher conductivity (the mismatch of conductivity relative to the sample matrix), the prolonged migration time led to peak broadening as a result of diffusion. Although curve c (30 mM BGE) reveals the best preconcentration ability to ALA, the poor resolution between DHPY and PY limited its application to clarify the degradation manner of ALA in vitro or in vivo, which is also an important issue in ALA‐PDT treatment . Therefore, 40 mM borate buffer (pH 9.3) with conductivity of 4.99 mS/cm was chosen as the optimum BGE.…”

Design, Synthesis and Photodynamic Antimicrobial Activity of Ruthenium Trischelate Diimine Complexes

“…This means that delivery of these drugs using solution, gel or patch-based dosage forms should not be problematic [19]. None of the compounds possessed a flat shape and planarity did not extend over the entire molecules, due to the coordinate bonds giving a threedimensional structure in each case (Fig.…”