Topical formulations of delta-aminolevulinic acid for the treatment of actinic keratosis: Characterization and efficacy evaluation.

Actinic keratosis (AK) is a pre-cancerous disease, with worldwide increasing incidence, which consists in squamous cutaneous lesion caused by excessive exposure to ultraviolet radiation. An established treatment option is photodynamic therapy (PDT), based on light, oxygen and a photosensitizer. The most widely used is 5-aminolevulinic acid (ALA) which however, being a hydrophilic molecule, has difficultly penetrating the skin to achieve the desired therapeutic effect. To solve this limit, the present study provides for the development of three galenic gel formulations (Natrosol, Sepigel and Carbopol) containing 10% w/w of ALA for the treatment of AK with PDT and their comparison with a lipophilic cream used in the Hospital. The aim of this study is to offer an appealing topical treatment that improves patients' observance and compliance. Formulations were characterized in terms of chemical, physical and microbiological stability, viscosity and pH. An HPLC-DAD analytical method was also developed and validated. Sepigel gel resulted the best gel formulation in terms of technological characteristics and stability. A comparative study between this gel and the lipophilic cream was assessed, by evaluating the therapeutic efficacy and the compliance of the patients.

Synthesis, conformational analysis and CB1 binding affinity of hairpin-like anandamide pseudopeptide mimetics.

We have designed, synthesized and evaluated the CB(1) binding affinity of a number of new conformationally restricted lipopeptides (1-17). All of them present some of the AEA key structural elements incorporated in a hairpinlike peptide framework. Among them, compounds 1-3 and 8 showed CB(1) affinities in competitive binding assays with K(i) values in the micromolar range (K(i) of AEA = 0.8 microM in the same assay). The remaining pseudopeptides showed little binding to the CB(1) receptor (with K(i) values >or= 50 microM). Conformational analysis on two representative compounds, performed by a combination of NMR studies, restrained molecular dynamics and QM calculations, allowed us to shed light on the structure-activity relationships (SAR), pointing to a correlation between the predominance of the hairpin-like structural motif and the CB(1) binding affinity. In a more general context, the present study may also prove useful in gaining additional insight into the biological relevance of the various AEA conformations.