ABSTRACT
The incidence of malignant melanoma is increasing at an alarming rate. As the clinical outcome of the disease strongly depends on the localization of the lesion, early detection at the initial stages of development is critical. Here, we suggest spatial characterization of melanoma based on the presence of endogenous stable free radicals in melanin pigments. Taking into account the abundance of these naturally occurring free radicals in proliferating melanocytes and their localization pattern, we hypothesized that electron paramagnetic resonance (EPR) imaging could be a unique tool for mapping melanomas with high sensitivity and high resolution. The potential of EPR to image melanoma samples was demonstrated in vitro in animal and human samples. Using EPR systems operating at low frequency, we were also able to record in vivo EPR spectra and images from the melanin present in a subcutaneous melanoma implanted in a mouse. In addition to the proof-of-concept and the achievement of providing the first non-invasive image of an endogenous radical, this technology may represent a key advance in improving the diagnosis of suspected melanoma lesions.
Subject(s)
Electron Spin Resonance Spectroscopy , Melanoma/pathology , Animals , Humans , Melanoma/diagnosis , Mice , Mice, Inbred C57BLABSTRACT
PURPOSE: To develop self-assembling systems increasing the solubility of poorly water-soluble drugs. METHODS: Low molecular weight liquid biodegradable copolymers were synthesized by ring-opening polymerization using caprolactone (CAP) and trimethylenecarbonate (TMC) as monomers. Various initiators were evaluated. The emulsifying and self-assembling properties were investigated by a water titration method. The self-assembling systems were characterized for size, shape, isotropic behavior, cloud point, surface charge, and critical micellar concentration in order to optimize the polymer synthesis. Finally, the improvement of solubility of model drugs was assessed. RESULTS: Only diblock monomethyl ether PEG-CAP/TMC copolymers synthesized with monomethyl ether polyethyleneglycol 550 to 2000 as initiator have shown self-assembling properties: upon dilution, these copolymers formed an isotropically clear solution with droplet sizes in the range of 20 to 100 nm. The hypothesis that these diblock polymers form micelles was confirmed by their low critical micellar concentration (10(-5) g/ml). The copolymers initated with mmePEG750 had a higher cloud point and better colloidal stability than those initiated with mmePEG 550. The solubility of the poorly water-soluble drugs was increased by 1 to 2 orders of magnitude. Good reproducibility was observed from batch to batch. CONCLUSIONS: The polyester diblock copolymer mmePEG750-CAP/TMC forms spontaneously stable micelles in aqueous medium and increases the solubility of lipophilic drugs. They are very promising vehicles for the oral delivery of poorly water-soluble drugs.
