Despite advances in the development of new therapeutic agents and diagnostic imaging techniques, the 5-year survival of osteosarcoma, the most common type of bone cancer, remains practically unaltered for the last three decades at around 60%. Nanoparticle-based carriers have emerged as new class of drug delivery systems that could potentially overcome conventional chemotherapy limitations, by promoting a better drug biodistribution profile by allowing a preferential accumulation of the drug in the desired tissue, while minimising non-targeted tissue toxicity, thus resulting in an improved overall therapeutic effectiveness. Hydroxyapatite nanoparticles (HANP) are known to be biocompatible and non-immunogenic and have shown to be preferentially accumulated in bone tissues being considered a promising carrier to bone tissues. Herein, we successfully synthesised mesoporous hydroxyapatite nanoparticles with mean size of 285.32 ± 10.29 nm and superficial area of 103.5 m/g, containing significant quantities of chemotherapeutic drug vincristine. A spectrophotometric method was developed and validated aiming to quantify the vincristine (VCR)-loaded in nanoparticles. Chorioallantoic membrane assay revealed relevant anti-angiogenic activity of system, leading to accentuated reduction in the number of blood vessels in fertilised eggs. Findings presented in this paper suggested that VCR-loaded HANP has a promising future as a nanocarrier for bone cancer treatment.

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Seventeen borneol esters (1-17) were synthesised by conventional and microwave-assisted methodology using DIC/DMAP, and seven are described for the first time (8, 9, 10, 12, 13, 16 and 17). The microwave-assisted methodology was carried out without use of solvents, displayed short reaction times, and showed equal or higher yields for all the long-chain esters and three aromatic compounds (11, 12 and 14) when compared to the conventional approach. All the borneol esters were evaluated against the bacteria Streptococcus sanguinis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and the fungus Candida albicans. Compounds 12, 13 and 14 displayed promising antibacterial activity with a MIC equal to ampicilin (62.5 mg mL) for some microorganisms. In fact, bornyl 3',4'-dimethoxybenzoate (13) was active against all tested bacteria and fungus.

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Sclareol (SC) is arousing great interest due to its cytostatic and cytotoxic activities in several cancer cell lines. However, its hydrophobicity is a limiting factor for its in vivo administration. One way to solve this problem is through nanoencapsulation. Therefore, solid lipid nanoparticles (SLN-SC) and nanostructured lipid carriers (NLC-SC) loaded with SC were produced and compared regarding their physicochemical properties. NLC-SC showed better SC encapsulation than SLN-SC and was chosen to be compared with free SC in human cancer cell lines (MDA-MB-231 and HCT-116). Free SC had slightly higher cytotoxicity than NLC-SC and produced subdiploid DNA content in both cell lines. On the other hand, NLC-SC led to subdiploid content in MDA-MB-231 cells and G2/M checkpoint arrest in HCT-116 cells. These findings suggest that SC encapsulation in NLC is a way to allow the in vivo administration of SC and might alter its biological properties.

The gastric healing and gastric ulcer recurrence preventive effect of Lupeol Stearate (LS) was measured in this study. To evaluate the gastric healing effect, rats were submitted to the 80% acetic acid-induced ulcer model and treated with vehicle (1 ml/kg, p.o.), LS (1 mg/kg, p.o.) or omeprazole (20 mg/kg, p.o.) twice a day for seven days. The gastric injury was evaluated macroscopically, histologically and histochemical; and biochemical parameters were also quantified. To evaluate the effects of LS on gastric ulcer recurrence, mice were ulcerated by gastric instillation of 10% acetic acid and treated with vehicle (1 ml/kg, p.o.), LS (1 mg/kg, p.o.) or ranitidine (20 mg/kg, p.o.) twice a day for ten days. Then, the ulcer recurrence in these animals was induced by IL- 1β (1 µg/kg i.p) at five day after the end of the treatment period. The area of the lesion recurred were measured, as well as the activity of myeloperoxidase and TNF levels. Oral treatment with LS accelerated gastric healing by 63% compared to the group treated with vehicle, which was also evidenced by histological improvement and increased production of mucin in the gastric epithelium. LS elevated the activity of the glutathione S-transferase and reduced the activity of myeloperoxidase, but did not change the levels of reduced glutathione or the activity of superoxide dismutase and catalase at the ulcer site in rats. Regarding the recurrence, the LS treatment reduced the recurred lesions, reducing MPO activity but not TNF levels at ulcer site. It can be concluded that LS promotes the healing of gastric lesions by favoring the mucus production and reducing the migration of neutrophils and that it can reduce the severity of the ulcer recurrence.

Objective. The focus of this study was to evaluate the gastric healing effect of lupeol stearate (LS) and its ability to minimize ulcer recurrence in rodents. Methods. To evaluate the gastric healing properties of LS, rats were subjected to 80% acetic acid-induced ulcer model and treated with vehicle, LS (1 mg/kg, p.o.), or omeprazole (20 mg/kg, p.o.), twice daily by seven days. The gastric ulcers were evaluated macroscopically, histologically, and biochemically. To evaluate the effects of LS in gastric ulcer recurrence, mice were ulcerated with 10% acetic acid and treated with vehicle, LS (1 mg/kg, p.o.), or ranitidine (100 mg/kg, p.o.), twice a day for ten days. Then, ulcer recurrence in these animals was induced by IL-1β at five days after the treatment period. Results. The oral treatment with LS accelerated gastric healing by 63% in rats compared to the vehicle group, evidenced by histological improvement and increased gastric mucin levels. Moreover, the gastric healing effects of LS in rats were accompanied by an elevation in glutathione S-transferase activity and a reduction in myeloperoxidase activity. Furthermore, the LS treatment reduced the recurred lesions in mice. Conclusions. The oral treatment of LS accelerates gastric healing in rats by favoring mucus production and reducing neutrophil migration, and it also can reduce ulcer recurrence. These data highlighted this compound as promising for developing new pharmacological strategies for the management of gastric ulcer.