Development of Liposomes Loaded with Chloroaluminum Phthalocyanine for Application of Photodynamic Therapy in Breast Cancer.

Chloraluminium phthalocyanine (ClAlPc) has potential therapeutic effect for the treatment of cancer; however, the molecule is lipophilic and may present self-aggregation which limits its clinical success. Thus, nanocarriers like liposomes can improve ClAlPc solubility, reduce off-site toxicity and increase circulation time. For this purpose, developing suitable liposomes requires the evaluation of different lipid compositions. Herein, we aimed to develop liposomes containing soy phosphatidylcholine (SPC), 1,2-distearoyl-sn-glycero- 3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPEPEG2000), cholesterol and oleic acid loaded with ClAlPc using the surface response methodology and the Box-Behnken design. Liposomes with particle size from 110.93 to 374.97 nm and PdI from 0.265 to 0.468 were obtained. The optimized formulation resulted in 69.09 % of ClAlPc encapsulated, with particle size and polydispersity index, respectively, at 153.20 nm and 0.309, providing stability and aggregation control. Atomic force microscopy revealed vesicles in a spherical or almost spherical shape, while the analyzes by Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR) suggested that the drug was adequately incorporated into the lipid bilayer of liposomes, in its amorphous state or molecularly dispersed. In vitro studies conducted in breast cancer cells (4T1) showed that liposome improved phototoxicity compared to the ClAlPc solution. ClAlPc-loaded liposomes also enhanced the production of ROS 3-fold compared to the ClAlPc solution. Finally, confocal microscopy and flow cytometry demonstrated the ability of the liposomes to enter cells and deliver the fluorescent ClAlPc photosensitizer with dose and time-dependent effects. Thus, this work showed that Box-Behnken factorial design was an effective strategy for optimizing formulation development. The obtained ClAlPc liposomes can be applied for photodynamic therapy in breast cancer cells.

Photodynamic effect of palladium porphyrin derived from cashew nut shell liquid against promastigote forms of Leishmania braziliensis.

Cutaneous leishmaniasis (CL) is a neglected tropical disease (NTD), endemic mainly in low-income countries that lack adequate basic health care. The emergence of resistant parasites to pentavalent antimonials has led to the search for new treatments for CL. Photodynamic therapy (PDT) is a promising non-invasive and less toxic alternative for the treatment of CL. The present work describes the synthesis, characterization and photodynamic effect against CL of a new metalloporphyrin Pd (II) meso-tetra[4-(2-(3-n-pentadecylphenoxy)ethoxy]phenylporphyrin (PdP) derived from the cashew nut shell liquid (CNSL). The PdP complex presented a singlet oxygen quantum yield of 0.49, favoring a type II photochemical reaction. The results of the photodynamic experiment carried out with PdP on the promastigote forms of Leishmania braziliensis indicated a mortality percentage of 70 % of the cells when compared to the control after exposure to blue light (λ = 420 nm). Besides this, the metalloporphyrin PdP did not show considerable toxicity to macrophages, indicating the cell viability of the compound. Therefore, this metalloporphyrin derived from biomass represents an interesting alternative as a potential therapeutic drug for the treatment of CL through PDT, especially for patients with intolerance to the chemotherapeutic drugs currently available.