Photodynamic therapy (PDT) is a medical treatment by which a combination of visible light and a sensitising drug causes the destruction of target cells. A drug without dark toxicity is introduced into the body and accumulates in rapidly dividing cells. Light of appropriate wavelength and fluence is then used to irradiate the target tissue. This activates the drug and elicits the toxic reaction in the presence of oxygen. To date, the applications of PDT have been limited mainly to areas of the body easily accessible to a laser or incoherent light source. Consequently, PDT has been largely investigated as a treatment for tumours and neoplasias of the skin, bladder, mouth and female reproductive tract. In case of topical application, compounds of high molecular weight (>500 daltons) have impaired abilities to cross the stratum corneum barrier of the skin. Therefore, despite a few isolated studies, pre-formed photosensitisers, which are generally large, highly conjugated molecules, are not commonly used in topical PDT. This, coupled with their inherent lack of selectivity, means that 5-aminolevulinic acid (ALA), with a molecular weight of 167.8 daltons, is the most frequently employed agent in modern topical PDT. The rapid development of the field of topical PDT based on ALA and its more lipophilic ester derivatives has led to the publication of numerous lab-based and clinical studies. The largely experimental nature of this area has meant that the vast majority of these reports have focussed primarily on the drugs and the outcomes of treatments. Due to the success of these initial investigations, topical PDT has become an established treatment option for a variety of surface lesions. The time has now come for a rational design of administration procedures and vehicles for optimised delivery of ALA and its derivatives. The process of rational dosage form design takes into account the physiochemical properties of the drug and dosage form, the nature of the biological barriers to drug delivery, the anatomy of the body site to which the drug is to delivered, and the desired drug release kinetics. Purpose-designed dosage forms for topical delivery of ALA or its esters for PDT include creams containing penetration enhancers, pressure sensitive patches and bioadhesive patches.
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