Combination of selol nanocapsules and magnetic hyperthermia hinders breast tumor growth in aged mice after a short-time treatment.

Short time treatment with reduced dosages of selol-loaded PLGA nanocapsules (NcSel) combined with magnetic hyperthermia (MHT) is evaluated in aged Erhlich tumor-bearing mice. Clinical, hematological, biochemical, genotoxic and histopathological parameters are assessed during 7 d treatment with NcSel and MHT, separately or combined. The time evolution of the tumor volume is successfully modeled using the logistic mathematical model. The combined therapy comprising NcSel and MHT is able to hinder primary tumor growth and a case of complete tumor remission is recorded. Moreover, no metastasis was diagnosed and the adverse effects are negligible. NcSel plus MHT may represent an effective and safe alternative to cancer control in aged patients. Future clinical trials are encouraged.

Adsorption of Vi Capsular Antigen of Salmonella Typhi in Chitosan-Poly (Methacrylic Acid) Nanoparticles.

The development of a nanoparticulate system for the carrier antigen is now an important tool in the vaccination process, since a smaller number of doses is necessary for effective immunization. Thus, in this work a nanoparticulate system using polymers of chitosan and poly (methacrylic acid) (CS-PMAA) to adsorb the Vi antigen of Salmonella Typhi was developed. CS-PMAA nanoparticles with different proportions of chitosan and poly (methacrylic acid) were obtained and reached sizes from 123.9 ± 2.48 to 234.9 ± 2.66 nm, and spherical shapes were seen in transmission microscopy. At pH 7.2, the nanoparticles had a cationic surface charge that contributed to the adsorption of the Vi antigen. Qualitative analyses of the isolated Vi antigen were performed using Fourier-transform infrared spectroscopy, which indicated the presence of all the characteristic bands of the capsular polysaccharide, and nuclear magnetic resonance, which showed signals for the five hydrogens and the N-acetyl and O-acetyl groups which are characteristic of the Vi antigen structure. In the adsorption kinetics study, the Vi capsular antigen, contained in a phosphate buffer solution of pH 7.2, experienced 55% adsorption on the 1-1% (CS-PMAA) nanoparticles. The adsorption kinetics results showed the ability of the nanoparticulate system to adsorb the Vi antigen.

Itraconazole encapsulated PLGA-nanoparticles covered with mannose as potential candidates against leishmaniasis.

Leishmaniasis is a neglected disease threatening over 350 million people. Antimonials are first-line drugs due to resistance and side effects there is a demand for alternative chemotherapy. Itraconazole (ITZ) is an antimycotic. It was encapsulated into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and covered with mannose. The NPs were 250 nm and -1.1 mV ± 0.7. PLGA-ITZ-mannose NPs presented a toxicity of 20.7% for J774 cells, and no toxicity for THP 1. The J774 cells were infected with three Leishmania promastigotes strains and treated with ITZ loaded PLGA NPs with/without mannose. The parasite percentage of L.(V.) panamensis intracellular amastigotes significantly (p < 0.01) decreased from 34.4% to 13.7% and 5.7% for PLGA-ITZ-mannose NPs and PLGA-ITZ NPs, respectively. For L.(L.) infantum there was a reduction (p < 0.001) from 18.1% to 4.8% and 8.3% for PLGA-ITZ-mannose NPs and PLGA-ITZ NPs, respectively. Further with L.(L.) braziliensis amastigotes there was a significant reduction (p < 0.001) from 54.9% to 28% and 21.1% for PLGA-ITZ-mannose NPs and PLGA-ITZ NPs, respectively. Adding mannose increased the efficacy PLGA-ITZ NPs against L.(L.) infantum, while it had no effect against L(V.) panamensis and L.(L.) braziliensis amastigotes. We recommend further investigation of PLGA-ITZ-mannose NPs in animal models to evaluate their potential. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000-000, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 680-687, 2019.

Different methods for diagnosis of sarcopenia and its association with nutritional status and survival in patients with advanced cancer in palliative care.

OBJECTIVES: The aim of the present study was to evaluate the association between sarcopenia, diagnosed by different muscle mass measurement techniques, with nutritional status and overall survival in patients with advanced cancer under palliative care. AIM: To investigate the association of sarcopenia, according to distinct muscle mass measurement methods, with nutritional status and overall survival (OS). METHODS: This observational and prospective study, including 334 patients, defined sarcopenia as reduced muscle mass and strength. Muscle mass was evaluated adopting 3 different methods, mid-upper arm muscle area (MUAMA), calf circumference (CC) and appendicular skeletal muscle mass (ASMI) described by Baumgartner (1998) and adjusted for height. Strength was defined using a handgrip dynamometer and OS was established based on a 90 days follow-up after inclusion date. Kaplan-Meier curves were conducted for survival analyzes and the association between sarcopenia and OS was evaluated by Cox regression model RESULTS: Prevalence of sarcopenia varied from 27-65% according to the method used to evaluate muscle mass. Malnutrition assessed by different parameters was significantly higher in patients with sarcopenia. Patients considered sarcopenic by MUAMA (43 versus 67 days, p<0.001), CC (44 versus 77 days, p<0.001) and ASMI (48 versus 75 days, p<0.001) had significantly lower OS compared to non-sarcopenic patients. Sarcopenia evaluated by MUAMA (HR, 1.57; 95% CI, 1.12-2.18) and CC (HR, 2.00; 95% CI, 1.45-2.76) showed a higher risk of mortality. CONCLUSION: Sarcopenia diagnosed by MUAMA and CC could predict mortality and CC proved to be the best prognostic method for estimating OS in patients with advanced cancer in palliative care.

In vitro assessment of anti-tumorigenic mechanisms and efficacy of NanoALA, a nanoformulation of aminolevulic acid designed for photodynamic therapy of cancer.

BACKGROUND: The development of nanocarriers is an important approach to increase the bioavailability of hydrophilic drugs in target cells. In this work, we evaluated the anti-tumorigenic mechanisms and efficacy of NanoALA, a novel nanoformulation of aminolevulic acid (ALA) based on poly(lactide-co-glycolide) (PLGA) nanocapsules designed for anticancer photodynamic therapy (PDT). METHODS: For this purpose, physicochemical characterization, prodrug incorporation kinetics, biocompatibility and photocytotoxicity tests, analysis of the cell death type and mitochondrial function, measurement of the intracellular reactive oxygen species production and DNA fragmentation were performed in murine mammary carcinoma (4T1) cells. RESULTS: NanoALA formulation, stable over a period of 90days following synthesis, presented hydrodynamic diameter of 220±8.7nm, zeta potential of -30.6mV and low value of polydispersity index (0.28). The biological assays indicated that the nanostructured product promotes greater ALA uptake by 4T1 cells and consequently more cytotoxicity in the PDT process. For the first time in the scientific literature, there is a therapeutic efficacy report of approximately 80%, after only 1h of incubation with 100µgmL-1 prodrug (0.6mM ALA equivalent). The mitochondria are probably the initial target of treatment, culminating in energy metabolism disorders and cell death by apoptosis. CONCLUSIONS: NanoALA emerges as a promising strategy for anticancer PDT. Besides being effective against a highly aggressive tumor cell line, the treatment may be economically advantageous because it allows a reduction in the dose and frequency of application compared to free ALA.