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Breast tumors represent the most common malignant tumors. Current treatments for humans and pets rely on tumor excision and adjuvant chemotherapy, which may affect both cancer cells and normal cells. Photodynamic therapy (PDT) is an approved treatment modality for a variety of cancers and was recently recommended as a first-line treatment for non-melanoma skin cancers for humans. The main purpose of the present study was to determine the efficacy of PDT using aluminum-chloride-phthalocyanine that is encapsulated in liposomes and LED as a light source to kill naturally occurring female dog breast cancer in vitro. The cytotoxicity behavior of the encapsulated photosensitizer in the dark and under irradiation using the 670 nm laser were investigated using classical trypan blue and MTT cell viability tests, acridine orange and ethidium bromide staining to label organelles, and cell morphology. Cell morphology was evaluated using light and electron microscopy. Our results demonstrate a reduced cell viability that is associated with morphologic alterations. The neoplasic cell destruction was predominantly mediated via a necrotic process, which was assayed using acridine orange and ethidium bromide staining. These findings were confirmed using light and electronic microscopy. The photosensitizer or laser irradiation alone did not induce cytotoxicity or morphological alterations, indicating the safety and efficacy of PDT with chloro-aluminum-phthalocyanine that was encapsulated in liposomes for the treatment of breast cancer cells in vitro.

Cutaneous leishmaniasis (CL) is a neglected tropical disease. The treatment is restricted to drugs, such as meglumine antimoniate and amphotericin B, that exhibit toxic effects, high cost, long-term treatment, and limited efficacy. The development of new alternative therapies, including the identification of effective drugs for the topical and oral treatment of CL, is of great interest. In this sense, a combination of topical photodynamic therapy (PDT) with chloroaluminum phthalocyanine liposomes (Lip-ClAlPc) and the oral administration of a self-emulsifying drug delivery system containing fexinidazole (SEDDS-FEX) emerges as a new strategy. The aim of the present study was to prepare, characterize, and evaluate the efficacy of combined therapy with Lip-ClAlPc and SEDDS-FEX in the experimental treatment of Leishmania (Leishmania) major. Lip-ClAlPc and SEDDS-FEX were prepared, and the antileishmanial efficacy study was conducted with the following groups: 1. Lip-ClAlPc (0.05 mL); 2. SEDDS-FEX (50 mg/kg/day); 3. Lip-ClAlPc (0.05 mL)+SEDDS-FEX (50 mg/kg/day) combination; 4. FEX suspension (50 mg/kg/day); and 5. control (untreated). BALB/c mice received 10 sessions of topical Lip-ClAlPc on alternate days and 20 consecutive days of SEDDS-FEX or FEX oral suspension. Therapeutical efficacy was evaluated via the parasite burden (limiting-dilution assay), lesion size (mm), healing of the lesion, and histological analyses. Lip-ClAlPc and SEDDS-FEX presented physicochemical characteristics that are compatible with the administration routes used in the treatments. Lip-ClAlPc+SEDDS-FEX led to a significant reduction in the parasitic burden in the lesion and spleen when compared to the control group (p < 0.05) and the complete healing of the lesion in 43% of animals. The Lip-ClAlPc+SEDDS-FEX combination may be promising for the treatment of CL caused by L. major. [ABSTRACT FROM AUTHOR]

• PDT as a potential strategy for the cutaneous leishmaniasis treatment. • Chloroaluminum phthalocyanine liposomes have good stability and can be used in PDT. • Chloroaluminum phthalocyanine liposomes reduces the leishmania load in lesion and spleen. In the Americas, one of the main causative species of cutaneous leishmaniasis is Leishmania (Leishmania) amazonensis. The systemic antimonials remain the most largely used option for disease control. However, this drug has significant toxicity. The development of new alternative therapies, including the identification of effective drugs for topical treatment of cutaneous leishmaniasis, is of utmost interest. In this sense, photodynamic therapy emerges as a new strategy. The aim of this study was to develop the chloroaluminum phthalocyanine-loaded liposome, characterize it, and evaluate its stability and efficacy in the topical treatment of cutaneous leishmaniasis caused by L. (L.) amazonensis. Liposomes composed of egg phosphatidylcholine were prepared by Bangham's method. Storage stability of phthalocyanine-loaded liposomes was evaluated at 30 and 60 days after preparation. For the in vivo evaluation, the animals were infected with L. (L.) amazonensis and divided into groups: chloroaluminium phthalocyanine-loaded liposome, blank liposome, meglumine antimoniate (200 mgSb+5/Kg/day), and control. The lesion size was determined weekly after the beginning of the treatment. Upon completion, parasites were recovered from the skin lesion and spleen and evaluated by limiting dilution assay. Chloroaluminum phthalocyanine-loaded liposomes were stable and showed adequate characteristics for topical administration. The topical chloroaluminum phthalocyanine-loaded liposome was as effective as systemic pentavalent antimony in reducing the parasitic load in the lesion and spleen in infected animals. The present study showed that photodynamic therapy with chloroaluminum phthalocyanine-loaded liposomes is a promising strategy for the treatment of American cutaneous leishmaniasis caused by L. (L.) amazonensis. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a technique employed in the treatment of several superficial infections, such as caries. PDT uses a non-toxic drug termed photosensitizer (PS) followed by light irradiation. The cytotoxic effects of the therapy are related to the production of reactive species produced after light activation of a photosensitizer, which reacts with surrounding molecules and disrupts several of the cell's functions. Within this context, this study aimed to develop a clinical protocol involving PDT application mediated by aluminum-chloride-phthalocyanine (AlClPc) entrapped in cationic liposomes against cariogenic bacteria in caries lesions. Cationic liposomes were used to delivery AlClPc preferentially to bacterial cells due to the strong anionic superficial charges of these cell types. The results are represented in two fundamental steps: (1) in vitro evaluation of AlClPc delivery to cariogenic bacteria and pulp cells, as well as its potential phototoxicity; (2) a clinical study involving volunteer patients that were treated with the PDT protocol mediated by AlClPc-cationic liposome. The main results showed that the AlClPc-cationic liposome was preferentially absorbed by bacterial cells compared to eukaryotic dental pulp cells, and it was efficient in the reduction of microbial load from bacterial cultures. In addition, the clinical study showed a mean reduction of 82% of total bacterial in the treated cavities after PDT application. Taken together, the results presented in this study showed that the antimicrobial PDT protocol mediated by cationic liposomes containing AlClPc is safety for clinical application and is efficient in the reduction of bacterial load in caries lesions. [ABSTRACT FROM AUTHOR]

The cellular uptake and antimycobacterial activity of usnic acid (UA) and usnic acid-loaded liposomes (UA-LIPOs) were assessed on J774 macrophages. The minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of UA and UA-LIPO against Mycobacterium tuberculosis were determined. Concentrations required to inhibit 50% of cell proliferation (IC50) were 22.5 (±0.60) and 12.5 (±0.26) μg/ml, for UA and UA-LIPO, respectively. The MICs of UA and UA-LIPO were 6.5 and 5.8 μg/mL, respectively. The MBC of UA-LIPO was twice as low (16 μg/mL) as that of UA (32 μg/mL). An improvement in the intracellular uptake of UA-LIPO was found (21.6 × 104 ± 28.3 × 102 c.p.s), in comparison with UA (9.5 × 104 ± 11.4 × 102 c.p.s). In addition, UA-LIPO remains much longer inside macrophages (30 hours). All data obtained from the encapsulation of usnic acid into liposomes as a drug delivery system (DDS) indicate a strong interaction between UA-liposomes and J774 macrophages, thereby facilitating UA penetration into cells. Considering such a process as ruling the Mycobacterium-transfection by magrophages, we could state that associating UA with this DDS leads to an improvement in its antimycobacterial activity. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is a skin cancer therapy that still has limitations due to the low penetration of this drug into the skin. We have proposed in this work a delivery system for 5-ALA based on liposomes having lipid composition similar to the mammalian stratum corneum (SCLLs) in order to optimize its skin delivery in Photodynamic Therapy (PDT) of skin cancers.Methods: SCLLs were obtained by reverse phase evaporation technique and size distribution of the vesicles was determinated by photon correlation spectroscopy. In vitro permeation profile was characterized using hairless mouse skin mounted in modified Franz diffusion cell.Results: Size exclusion chromatography on gel filtration confirmed vesicle formation. SCLLs obtained by presented a degree of encapsulation of 5-ALA around 5.7%. A distribution of vesicle size centering at around 500 nm and 400 nm respectively for SCLLs and SCLLs containing 5-ALA was found. In vitro 5-ALA permeation study showed that SCLLs preparations presented higher skin retention significantly (p < 0.05) on the epidermis without SC + dermis, with a decreasing of skin permeation compared to aqueous solution.Conclusions: The in vitro delivery performance provided by SCLLs lead to consider this systems adequate for the 5-ALA-PDT of skin cancer, since SCLLs have delivered 5-ALA to the target skin layers (viable epidermis + dermis) to be treated by topical PDT of skin cancer. [ABSTRACT FROM AUTHOR]