In vitro skin permeation and retention of 5-aminolevulinic acid ester derivatives for photodynamic therapy

Influence of ceramide 2 on in vitro skin permeation and retention of 5-ALA and its ester derivatives, for Photodynamic Therapy

“…The same result in SC was observed by De Rosa et al (2003) for these drugs dispersed in an O/W emulsion, that is, the H-ALA retention in SC was also higher than 5-ALA and O-ALA.…”

“…However, the K SC/W of ALA esters (De Rosa et al, 2003) is much higher than the K S/W (Table II). These results indicated that the affinity of ALA esters for the SC is significantly higher than their affinity for the viable epidermis, pointing out retention of these esters in the most external barrier of the skin, i.e, the SC.…”

“…Recently, stratum corneum/water partition coefficients of 5-ALA and several alkyl esters were determined by De Rosa et al (2003) and also showed this effect, that is, an increase in the K with the alkyl chain length of the ALA ester.…”

“…There are several methods to improve 5-ALA skin penetration: (i) changing the drug formulation by adding a penetration enhancer (Pierre et al, 2006) or by packaging it into a drug delivery system, e.g., liposomes (Pierre et al, 2001); (ii) applying an electrical current (Lopez et al, 2001); (iii) modulating the biosynthetic pathway by the addition of iron chelators (Curnow et al, 1998) and (iv) increasing the lipophilicity of 5-ALA by its own esterification, for example (De Rosa et al, 2003). In topical applications, esters can improve penetration depth as a result of their enhanced lipophilicity and also yield a more homogeneous tissue distribution (Van Den Akker et al, 2000) leading to shorter application times, lower drug doses, lower cost, reduced side-effects (e.g.…”

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

“…ALA is a small molecule which when applied topically can diffuse into cutaneous tissue but because it is hydrophilic it has limited capacity to cross tissue barriers such as the hydrophobic stratum corneum of the skin. Therefore the ester derivative, MAL, with greater lipophilicity (provided by the additional alkyl chain), can be utilised as it is expected to cross the stratum corneum more easily than ALA [13]. Past studies by Peng et al have reported that in lesions of up to 2 mm thickness the application of MAL for 3 hours showed the highest ratio of PpIX fluorescence depth to tumor depth [7], in contrast to the more limited penetration with ALA [8].…”