A Clinical Investigation to Determine the Effect of Pressure Injection on the Penetration of Topical Methyl Aminolevulinate into Nodular Basal Cell Carcinoma of the Skin

Abstract

This investigation considered a novel method of enhancing penetration of the topical photosensitizing agent methyl aminolevulinate (MAL) into nodular basal cell carcinomas (BCCs) using an oxygen pressure injection device. Oxygen pressure injection (OPI) is a method to drive compounds into skin using pressured oxygen. The study was an observer-blinded pilot of a single application of MAL to nBCCs, with or without the use of OPI. The BCCs were then excised at different time intervals (0-180 min) and the depth of penetration of the MAL examined using microscopic fluorescence photometry to detect the production of the naturally fluorescent active photosensitiser protoporphyrin IX (PpIX). A highly selective and homogeneous distribution of MAL-induced porphyrin fluorescence was seen in all nBCC tumors studied, and showed a high lesion-to-normal-tissue ratio with very little fluorescence in the surrounding normal tissue. Although it was difficult to compare quantitatively, as individual tumors in each of the different study groups varied, a definite trend of increase in relative tumor concentration of MAL-induced PpIX was observed over time, and this was enhanced when OPI was employed.

The time-dependent accumulation of protoporphyrin IX fluorescence in nodular basal cell carcinoma following application of methyl aminolevulinate with an oxygen pressure injection device

“…All the images were exported and analyzed in NIH ImageJ software To compare the relative depth of fluorescence between groups; the higher pressure OPI device, the standard pressure OPI device [22], the standard treatment group (where no OPI device employed to apply the Metvix® cream) [22] and the combined OPI measurements, these data were analyzed using the non-parametric Mann Whitney U test.…”

“…The button was pressed six times over each lesion, with the treatment time for each metered application being 0.1 second. This arbitrary figure was chosen in our previous study [22] to try and ensure maximal effect and was therefore used consistently in each case. Once Metvix® cream is applied to the lesion the principle of the OPI device is simply to increase the penetration of the active ingredient MAL through the skin under the action of the pulsed pressure of concentrated oxygen.…”

“…Results showed that over time, for all patients, an increase in PpIX fluorescence was observed. Notably, when the standard pressure OPI device was employed, PpIX fluorescence was enhanced relative to the standard treatment group which simply had the Metvix® cream applied as per normal practice without an OPI device [22]. Following Metvix® application with the standard pressure OPI device after 30, 60, 120 and 180 minutes the mean relative depth of PpIX fluorescence increased by 25%, 49%, 12% and 16%, respectively compared to the groups where the Metvix® cream was applied without OPI.…”

“…DMSO [16] or glycolic acid [17]), iontophoresis [18], lesion surface preparation (e.g. gentle curettage [19] or tape-stripping [20]), elevating skin temperature [21], pressurized oxygen [22], micro-needle puncture [23], nanoemulsions [24] and needleless jet injection [25].…”

“…A previous study [22] conducted by our group with a (standard pressure) oxygen pressure injection (OPI) device recruited 6 patients into each of five study groups (0, 30, 60, 120 or 180 minutes Metvix® application) with half the nBCC lesions in each group receiving standard pressure OPI (a metered dosage of oxygen released at 2.0 bar). Results showed that over time, for all patients, an increase in PpIX fluorescence was observed.…”