Stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid in photodynamic therapy of skin cancer: preparation and in vitro permeation study

Abstract

Background: Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is a skin cancer therapy that still has limitations due to the low penetration of this drug into the skin. We have proposed in this work a delivery system for 5-ALA based on liposomes having lipid composition similar to the mammalian stratum corneum (SCLLs) in order to optimize its skin delivery in Photodynamic Therapy (PDT) of skin cancers.

Methods: SCLLs were obtained by reverse phase evaporation technique and size distribution of the vesicles was determinated by photon correlation spectroscopy. In vitro permeation profile was characterized using hairless mouse skin mounted in modified Franz diffusion cell.

Results: Size exclusion chromatography on gel filtration confirmed vesicle formation. SCLLs obtained by presented a degree of encapsulation of 5-ALA around 5.7%. A distribution of vesicle size centering at around 500 nm and 400 nm respectively for SCLLs and SCLLs containing 5-ALA was found. In vitro 5-ALA permeation study showed that SCLLs preparations presented higher skin retention significantly (p < 0.05) on the epidermis without SC + dermis, with a decreasing of skin permeation compared to aqueous solution.

Conclusions: The in vitro delivery performance provided by SCLLs lead to consider this systems adequate for the 5-ALA-PDT of skin cancer, since SCLLs have delivered 5-ALA to the target skin layers (viable epidermis + dermis) to be treated by topical PDT of skin cancer.

Figure 1

Elution profile of: (a) SCLLs and (b) 5-ALA solutions using size exclusion chromatography on a Sephadex G-75 column.

Figure 2

Amount of 5-ALA permeated (μg/cm²) through hairless mouse skin from the 5-ALA aqueous solution (black star) and SCLLs (square), as a function of time (hours).

Figure 3

Amount of 5-ALA (μg) permeated and retained in the SC and epidermis without SC + dermis after 36 hours of in vitro permeation study. Errors bars indicate standard deviation of the mean. Statistical significance indicated by one-tailed Student's t test: (^*) P < 0.05) and (^**) P < 0.001.