With the development of the nanotechnology, the influence of nanoparticulate carries system on skin penetration of drugs has become a subject so much studied. Despite this, the skin penetration of polymer nanoparticles is still quite controversial. Recent studies, some of that realized by our group, presented that nanoparticles can permeate the skin just a low concentration and when it has specific surface characteristics. To increase the penetration of nanoparticles through the skin, the application of physical methods such as iontophoresis (object of this study) is the alternative that can be promising but it is very recent. For example, studies about the influence of iontophoresis on the penetration of nanoparticles into tumor tissue are not found in the literature. Thus, the aim of the study is to evaluate the influence of PAMAM G4-OH dendrimers and iontophoresis on the tumor penetration of protoporphyrin IX (PpIX) in skin tumors that will be induced in Nude BalbC mice and to evaluate regression of tumor after photodynamic therapy (PDT). The PpIX, photodynamic active substance, is used in PDT, however, due to its high lipophilicity it presents difficulties to spread to deeper layers through the skin, so it not can be administered topically. Thus, carries system are needed to facilitate the penetration of drug through the main barrier of the skin, the stratum corneum. The PAMAM G4-OH dendrimer was the carry system chosen for this project it to modulate the penetration of PpIX. Dendrimers are polymeric nanoparticles that can increase the solubility of PpIX forming a complex with this drug. The study with complexes of PpIX - PAMAM G4-OH has been realized, in vitro in healthy skin, by ours group. The results were positive to influence on the penetration of the dendrimers and activity fotocitotóxica of PpIX. In this study, the penetration of free PpIX and complexed PpIX will be evaluated in vivo study after passive and iontophoretic topical application in skin tumor that was induced in immunosuppressed mice. The influence of iontophoresis and dendrimer nanoparticle in the penetration and delivery of PpIX through the skin in the tumor will be evaluated by confocal microscopy and the PpIX will be quantified after removal of the tumor by spectrofluorimetry. In a second step, the treated tumor will be submitted to PDT and tumor regression will be evaluated. We expected that the application of iontophoresis in the dispersion of dendrimers nanoparticles with PpIX will increase the penetration and delivery of the drug in the tumor; it could make the topical PDT with this drug more effective.
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