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| Author(s): |
Talita Cesarim Mendonça
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2024-07-31 |
| Examining board members: |
Eneida de Paula;
Viviane Aparecida Guilherme Damasio;
Wagner José Fávaro
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| Advisor: | Eneida de Paula; Ludmilla David de Moura |
| Abstract | |
Since the 1990s, breast cancer has been the most frequent solid neoplasm among women, worldwide, being the second most common cause of death from cancer in this group. Doxorubicin (DOX) is an antineoplastic antibiotic from the anthracycline group widely used in the treatment of breast cancer and with significant activity against tumors refractory to other drugs. Photodynamic therapy (PDT) is another treatment explored in oncology, in which a photochemical reaction causes selective destruction of a tissue, after irradiation of a photosensitizing agent. Nanostructured lipid carriers (NLC) are nanoparticles made up of a mixture of lipids (solid and liquid) and stabilized by a surfactant. These nanoparticles are efficient carriers for molecules that are poorly soluble in water, such as DOX and photosensitizer chloro-aluminum phthalocyanine (PcAlCl). The present research aimed to develop an optimized formulation of nanostructured lipid carriers containing the antineoplastic DOX and the photosensitizer PcAlCl, aiming the treatment of breast cancer. Formulations were prepared by experimental design and the optimized one (NLCDOX/PcAlCl) and its control (NLCDOX, NLCFtClAl, NLCCTL) were characterized regarding size, polydispersity indexes (PDI, Span), Zeta potential (ZP), number of nanoparticles in suspension, pH, by infrared spectroscopy and electron cryomicroscopy. The optimized formulation showed a monodisperse population (PDI = 0.164 ± 0.03; Span index = 0.554) of particles with an average diameter of 160.8 ± 1.9 nm, ZP = -27.0 ± 0.9 mV, 5.30 ± 0.01 x 1013 nanoparticles/mL and a pH of 5.30 ± 0.01. The NLC showed a spherical morphology, and 12 months shelf-stability, under refrigeration (2-8ºC) or at room temperature (25ºC). Subsequently, an in vitro study to evaluate the cytotoxicity of the nanoparticles was carried with two mammary adenocarcinoma lineages, from mice (4T1), and human (MCF-7) as well as in normal murine fibroblasts (NIH/3T3), by the MTT test and (fluorescence microscopy and phase-contrast) morphological analyses of post-treatment cells. In these tests, the power (9 and 18 J/cm2) of the 660 nm LED used for PDT application was also evaluated. Cell viability assays showed that CLNPcAlCl was toxic against the two cancer cell lines tested, and even more after irradiation. This work reports the development of a stable nanotechnological formulation that, carrying a chemotherapeutic agent and a photosensitizer, was found efficient and with a potential for the in vivo treatment of breast cancer (AU) | |
| FAPESP's process: | 21/02617-1 - Photodynamic therapy with chlorine-aluminum phalocyanine in nano-structured lipid carriers containing doxorrubicin to treat breast cancer |
| Grantee: | Talita Cesarim Mendonça Bolline |
| Support Opportunities: | Scholarships in Brazil - Master |