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The challenge was always great for lipophilic photosensitizer use in the photodynamic therapy (PDT) for treatment of internal body diseases. Photosensitizer metabolism in liver, incompatibility of the molecules in the gastric acid, aggregation in the bloodstream, opsonization of molecules and phagocyting process hamper the application of the free lipophilic photosensitizer in disease treatment using PDT. This problem has been partially resolved using the drug delivery system to encapsulate the photosensitizer. Many studies have been reported using polymeric nanoparticles to encapsulate the lipophilic photosensitizer showing excellent results for PDT, but few nanoparticulate formulations are available at the pharmacies. The absence of deep knowledge about the influence of synergic effect of parameters used in the nanoparticle preparation on its properties, the photobleaching process of encapsulated photosensitizer and the molecule aggregation into the nanoparticle can decrease the photodynamic efficacy for the lipophilic photosensitizer. Our research group has studied the influence of many parameters on the nanoparticulate properties of several encapsulated phthalocyanines and porphyrin using factorial design, evaluating the free and encapsulated compound aggregation, efficacy to reduce the viability of cancer cells, the photooxidation of the biomolecules and the influence of photobleaching. This work shows the most important results to be consider in the optimization of the polymeric nanoparticle.

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