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 6 x 7 arrays of microneedles 270 microm in height, with a diameter of 240 mum at the base and an interspacing of 750 microm 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 photosensitizer 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.
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK. r.donnelly@qub.ac.uk
Ryan F
RF
Donnelly
Desmond I J
DI
Morrow
Paul A
PA
McCarron
A David
AD
Woolfson
Anthony
A
Morrissey
Petras
P
Juzenas
Asta
A
Juzeniene
Vladimir
V
Iani
Helen O
HO
McCarthy
Johan
J
Moan
D000279:Administration, Cutaneous; D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D005260:Female; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009339:Needles; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects* / Q000648:ultrastructure; D013552:Swine
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid