Microneedle-mediated intradermal delivery of 5-aminolevulinic acid: potential for enhanced topical photodynamic therapy

Photodynamic therapy of deep or nodular skin tumours is currently limited by the poor tissue penetration of the porphyrin precursor 5-aminolevulinic acid (ALA). In this study, silicon microneedle arrays were used, for the first time, to enhance skin penetration of ALA in vitro and in vivo. Puncturing excised murine skin with 6x7 arrays of microneedles 270 mum in height, with a diameter of 240 mum at the base and an interspacing of 750 mum led to a significant increase in transdermal delivery of ALA released from a bioadhesive patch containing 19 mg ALA cm(-2). Microneedle puncture enhanced ALA delivery to the upper regions of excised porcine skin but, at mean depths of 1.875 mm, ALA concentrations were similar to control values, possibly reflecting binding of ALA by tissue components. However, and importantly, in vivo experiments using nude mice showed that microneedle puncture could reduce application time and ALA dose required to induce high levels of the photosensitiser protoporphyrin IX in skin. This clearly has implications for clinical practice, as shorter application times would mean improved patient and clinician convenience and also that more patients could be treated in the same session. As ALA is expensive and degrades rapidly via a second order reaction, reducing the required dose is also a notable advantage.

Interstitial cells of blood vessels

Blood vessels are made up of several distinct cell types. Although it was originally thought that the tunica media of blood vessels was composed of a homogeneous population of fully differentiated smooth muscle cells, more recent data suggest the existence of multiple smooth muscle cell subpopulations in the vascular wall. One of the cell types contributing to this heterogeneity is the novel, irregularly shaped, noncontractile cell with thin processes, termed interstitial cell, found in the tunica media of both veins and arteries. While the principal role of interstitial cells in veins seems to be pacemaking, the role of arterial interstitial cells is less clear. This review summarises the knowledge of the functional and structural properties of vascular interstitial cells accumulated so far, offers hypotheses on their physiological role, and proposes directions for future research.