Development and ex vivo evaluation of 5-aminolevulinic acid-loaded niosomal formulations for topical photodynamic therapy.
The objective of this study was the development of a niosomal formulation for improving skin permeation and penetration of 5-aminolevulinic acid (ALA) in the treatment of skin malignancies by photodynamic therapy (PDT). Different niosomal dispersions were prepared, using two different preparation methods. The effect of addition to a classic formulation, consisting in an equimolar Span 60-cholesterol mixture, of two different edge activators, dicethyl-phosphate (DCP) and sodium cholate (SC), and of the presence of ethanol on the vesicle properties and stability was evaluated. Selected formulations were loaded with the drug and evaluated for physicochemical and stability properties and encapsulation efficiency. Classic and elastic DCP-containing niosomes were the only formulations able to effectively incorporate the drug without instability problems. Ex vivo permeation and penetration studies through excised human skin showed that both the niosomal formulations were significantly more effective in improving ALA skin delivery than the simple aqueous drug solution commonly used in clinical practice, allowing, respectively, an increase of about 80 and 40% of the drug permeated amount and of about 100 and 50% of the drug retained into the skin. These results lead to consider the developed formulations potentially useful for improving ALA bioavailability and therapeutic effectiveness in skin malignancies treatment by topical PDT.
Department of Chemistry, University of Firenze, Polo Scientifico di Sesto Fiorentino, 50019 Sesto Fiorentino (Firenze), Italy.
Marco
M
Bragagni
Department of Chemistry, University of Firenze, Polo Scientifico di Sesto Fiorentino, 50019 Sesto Fiorentino (Firenze), Italy.
Andrea
A
Scozzafava
MST Center, Tuscan Orthopedic Institute Piero Palagi, University of Firenze, Viale Michelangelo 41, 50125 Firenze, Italy.
Antonio
A
Mastrolorenzo
Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Firenze, Polo Scientifico di Sesto Fiorentino, 50019 Sesto Fiorentino (Firenze), Italy.
Claudiu T
CT
Supuran
Department of Chemistry, University of Firenze, Polo Scientifico di Sesto Fiorentino, 50019 Sesto Fiorentino (Firenze), Italy. Electronic address: paola.mura@unifi.it.
Paola
P
Mura
D000279:Administration, Cutaneous; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004355:Drug Stability; D006801:Humans; D008081:Liposomes; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D012869:Skin Absorption; D013535:Suspensions / Q000008:administration & dosage / Q000737:chemistry
D004337:Drug Carriers; D008081:Liposomes; D013535:Suspensions; D000622:Aminolevulinic Acid
5-Aminolevulinic acid; Edge activators; Ex-vivo skin permeation; Ex-vivo skin-penetration; Niosomes; Photodynamic therapy